Tracking Number Ri 26 406 315 9 Bg

2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)

Borja Ibanez,

Borja Ibanez

(Chairperson) (Spain)

* Corresponding authors. The two chairmen contributed equally to the document: Borja Ibanez, Director Clinical Research, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain; Department of Cardiology, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain; and CIBERCV, Spain. Tel: +34 91 453.12.00 (ext: 4302), Fax: +34 91 453.12.45, E-mail: bibanez@cnic.es or bibanez@fjd.es. Stefan James, Professor of Cardiology, Department of Medical Sciences, Scientific Director UCR, Uppsala University and Sr. Interventional Cardiologist, Department of Cardiology Uppsala University Hospital UCR Uppsala Clinical Research Center Dag Hammarskjölds väg 14B SE-752 37 Uppsala, Sweden. Tel: +46 705 944 404, Email: stefan.james@ucr.uu.se

Search for other works by this author on:

Stefan James,

Stefan James

(Chairperson) (Sweden)

* Corresponding authors. The two chairmen contributed equally to the document: Borja Ibanez, Director Clinical Research, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain; Department of Cardiology, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain; and CIBERCV, Spain. Tel: +34 91 453.12.00 (ext: 4302), Fax: +34 91 453.12.45, E-mail: bibanez@cnic.es or bibanez@fjd.es. Stefan James, Professor of Cardiology, Department of Medical Sciences, Scientific Director UCR, Uppsala University and Sr. Interventional Cardiologist, Department of Cardiology Uppsala University Hospital UCR Uppsala Clinical Research Center Dag Hammarskjölds väg 14B SE-752 37 Uppsala, Sweden. Tel: +46 705 944 404, Email: stefan.james@ucr.uu.se

Search for other works by this author on:

Stefan Agewall,

Search for other works by this author on:

Manuel J Antunes,

Manuel J Antunes

(Portugal)

Search for other works by this author on:

Chiara Bucciarelli-Ducci,

Chiara Bucciarelli-Ducci

(UK)

Search for other works by this author on:

Héctor Bueno,

Search for other works by this author on:

Alida L P Caforio,

Alida L P Caforio

(Italy)

Search for other works by this author on:

Filippo Crea,

Search for other works by this author on:

John A Goudevenos,

John A Goudevenos

(Greece)

Search for other works by this author on:

Sigrun Halvorsen,

Sigrun Halvorsen

(Norway)

Search for other works by this author on:

... Show more

*

ESC Committee for Practice Guidelines (CPG) and National Cardiac Societies document reviewers: listed in the Appendix.

*

ESC entities having participated in the development of this document: Associations: Acute Cardiovascular Care Association (ACCA), European Association of Preventive Cardiology (EAPC), European Association of Cardiovascular Imaging (EACVI), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Heart Rhythm Association (EHRA), Heart Failure Association (HFA). Councils: Council on Cardiovascular Nursing and Allied Professions (CCNAP), Council for Cardiology Practice (CCP). Working Groups: Cardiovascular Pharmacotherapy, Cardiovascular Surgery, Coronary Pathophysiology and Microcirculation, Myocardial and Pericardial Diseases, Thrombosis.

*

The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC (journals.permissions@oxfordjournals.org).

*

Disclaimer. The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication. The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver. Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

Author Notes

Published:

26 August 2017

Guidelines, Acute coronary syndromes, Acute myocardial infarction, Antithrombotic therapy, Antithrombotics, Emergency medical system, Evidence, Fibrinolysis, Ischaemic heart disease, Primary percutaneous coronary intervention, Quality indicators, MINOCA, Reperfusion therapy, Risk assessment, Secondary prevention, ST-segment elevation

The disclosure forms of all experts involved in the development of these guidelines are available on the ESC website www.escardio.org/guidelines

For the Web Addenda which include background information and detailed discussion of the data that have provided the basis for the recommendations see https://academic.oup.com/eurheartj/article-lookup/doi/10.1093/eurheartj/ehx393#supplementary-data.

Click here to access the web addenda

Table of Contents

• Abbreviations and acronyms    3

• 1. Preamble    5

• 2. Introduction    6

•  2.1 Definition of acute myocardial infarction    6

•  2.2 Epidemiology of ST-segment elevation myocardial infarction    6

• 3. What is new in the 2017 version? 7

• 4. Emergency care    8

•  4.1 Initial diagnosis    8

•  4.2 Relief of pain, breathlessness, and anxiety    9

•  4.3 Cardiac arrest    10

•  4.4 Pre-hospital logistics of care    10

•   4.4.1 Delays    10

•   4.4.2 Emergency medical system    12

•   4.4.3 Organization of ST-segment elevation myocardial infarction treatment in networks    12

• 5. Reperfusion therapy    13

•  5.1 Selection of reperfusion strategies    13

•  5.2 Primary percutaneous coronary intervention and adjunctive therapy    16

•   5.2.1 Procedural aspects of primary percutaneous coronary intervention    16

•   5.2.2 Periprocedural pharmacotherapy    18

•  5.3 Fibrinolysis and pharmacoinvasive strategy    20

•   5.3.1 Benefit and indication of fibrinolysis    20

•   5.3.2 Pre-hospital fibrinolysis    21

•   5.3.3 Angiography and percutaneous coronary intervention after fibrinolysis (pharmacoinvasive strategy) 21

•   5.3.4 Comparison of fibrinolytic agents    22

•   5.3.5 Adjunctive antiplatelet and anticoagulant therapies    22

•   5.3.6 Hazards of fibrinolysis    23

•   5.3.7 Contraindications to fibrinolytic therapy    23

•  5.4 Coronary artery bypass graft surgery    23

• 6. Management during hospitalization and at discharge    24

•  6.1 Coronary care unit/intensive cardiac care unit    24

•  6.2 Monitoring    24

•  6.3 Ambulation    24

•  6.4 Length of stay    24

•  6.5 Special patient subsets    25

•   6.5.1 Patients taking oral anticoagulation    25

•   6.5.2 Elderly patients    25

•   6.5.3 Renal dysfunction    25

•   6.5.4 Non-reperfused patients    25

•   6.5.5 Patients with diabetes    26

•  6.6. Risk assessment    28

•   6.6.1 Clinical risk assessment    28

•   6.6.2 Non-invasive imaging in management and risk stratification    28

• 7. Long-term therapies for ST-segment elevation myocardial infarction    29

•  7.1 Lifestyle interventions and risk factor control    29

•   7.1.1 Smoking cessation    29

•   7.1.2 Diet, alcohol, and weight control    29

•   7.1.3 Exercise-based cardiac rehabilitation    30

•   7.1.4 Resumption of activities    30

•   7.1.5 Blood pressure control    30

•   7.1.6 Adherence to treatment    30

•  7.2 Antithrombotic therapy    30

•   7.2.1 Aspirin    30

•   7.2.2 Duration of dual antiplatelet therapy and antithrombotic combination therapies    31

•  7.3 Beta-blockers    32

•   7.3.1 Early intravenous beta-blocker administration    32

•   7.3.2 Mid- and long-term beta-blocker treatment    32

•  7.4 Lipid-lowering therapy    32

•  7.5 Nitrates    33

•  7.6 Calcium antagonists    33

•  7.7 Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers    33

•  7.8 Mineralocorticoid/aldosterone receptor antagonists    33

• 8. Complications following ST-segment elevation myocardial infarction    37

•  8.1 Myocardial dysfunction    37

•   8.1.1 Left ventricular dysfunction    37

•   8.1.2 Right ventricular involvement    37

•  8.2 Heart failure    37

•   8.2.1 Clinical presentations    37

•   8.2.2 Management    37

•  8.3 Management of arrhythmias and conduction disturbances in the acute phase    39

•   8.3.1 Supraventricular arrhythmias    39

•   8.3.2 Ventricular arrhythmias    40

•   8.3.3 Sinus bradycardia and atrioventricular block    41

•  8.4 Mechanical complications    42

•   8.4.1 Free wall rupture    42

•   8.4.2 Ventricular septal rupture    42

•   8.4.3 Papillary muscle rupture    42

•  8.5 Pericarditis    42

•   8.5.1 Early and late (Dressler syndrome) infarct-associated pericarditis    42

•   8.5.2 Pericardial effusion    42

• 9. Myocardial infarction with non-obstructive coronary arteries    42

• 10. Assessment of quality of care    42

• 11. Gaps in the evidence and areas for future research    44

• 12. Key messages    46

• 13. Evidenced-based 'to do and not to do' messages from the Guidelines    47

• 14. Web addenda    50

• 15. Appendix    50

• 16. References    51

Abbreviations and acronyms

Abbreviations and acronyms

Abbreviations and acronyms

• ACE

  angiotensin-converting enzyme

• ACCA

  Acute Cardiovascular Care Association

• ACS

• AF

• ALBATROSS

  Aldosterone Lethal effects Blockade in Acute myocardial infarction Treated with or without Reperfusion to improve Outcome and Survival at Six months follow-up

• AMI

  acute myocardial infarction

• ARB

  angiotensin II receptor blocker

• ASSENT 3

  ASsessment of the Safety and Efficacy of a New Thrombolytic 3

• ATLANTIC

  Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery

• ATLAS ACS 2–TIMI 51

  Anti-Xa Therapy to Lower cardiovascular events in Addition to Standard therapy in subjects with Acute Coronary Syndrome–Thrombolysis In Myocardial Infarction 51

• ATOLL

  Acute myocardial infarction Treated with primary angioplasty and inTravenous enOxaparin or unfractionated heparin to Lower ischaemic and bleeding events at short- and Long-term follow-up

• AV

• b.i.d.

• BMI

• BMS

• BNP

  B-type natriuretic peptide

• CABG

  coronary artery bypass graft surgery

• CAD

• CAPITAL AMI

  Combined Angioplasty and Pharmacological Intervention versus Thrombolytics ALone in Acute Myocardial Infarction

• CCNAP

  Council on Cardiovascular Nursing and Allied Professions

• CCP

  Council for Cardiology Practice

• CCU

• CHA₂DS₂-VASc

  Cardiac failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled) – VAScular disease, Age 65–74 and Sex category (Female)

• CI

• CKD

• CMR

  cardiac magnetic resonance

• CPG

  Committee for Practice Guidelines

• CRISP AMI

  Counterpulsation to Reduce Infarct Size Pre-PCI-Acute Myocardial Infarction

• CT

• COMFORTABLE- AMI

  Effect of biolimus-eluting stents with biodegradable polymer vs. bare-metal stents on cardiovascular events among patients with acute myocardial infarction trial

• Compare-Acute

  Comparison Between FFR Guided Revascularization Versus Conventional Strategy in Acute STEMI Patients With Multivessel disease trial

• CURRENT- OASIS 7

  The Clopidogrel and aspirin Optimal Dose usage to reduce recurrent events–Seventh organization to assess strategies in ischaemic syndromes

• CvLPRIT

  Complete Versus Lesion-Only Primary PCI Trial

• DANAMI

  DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction

• DANAMI 3- DEFER

  DANAMI 3 – Deferred versus conventional stent implantation in patients with ST-segment elevation myocardial infarction

• DANAMI-3– PRIMULTI

  DANAMI 3 – Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease

• DAPT

  dual antiplatelet therapy

• DES

• EACVI

  European Association of Cardiovascular Imaging

• EAPC

  European Association of Preventive Cardiology

• EAPCI

  European Association of Percutaneous Cardiovascular Interventions

• EARLY-BAMI

  Early Intravenous Beta-Blockers in Patients With ST-Segment Elevation Myocardial Infarction Before Primary Percutaneous Coronary Intervention

• ECG

• ECLS

  extracorporeal life support

• ECMO

  extracorporeal membrane oxygenation

• eGFR

  estimated glomerular filtration rate

• EHRA

  European Heart Rhythm Association

• EMS

• EPHESUS

  Eplerenone Post-AMI Heart failure Efficacy and SUrvival Study

• ESC

  European Society of Cardiology

• EXAMINATION

  Everolimus-Eluting Stents Versus Bare-Metal Stents in ST-Segment Elevation Myocardial Infarction

• ExTRACT– TIMI 25

  Enoxaparin and Thrombolysis Reperfusion for Acute myocardial infarction Treatment–Thrombolysis In Myocardial Infarction

• FFR

• FMC

• FOCUS

  Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention

• FOURIER

  Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk trial.

• GP

• GRACE

  Global Registry of Acute Coronary Events

• GRACIA

  Grupo de Análisis de la Cardiopatía Isquémica Aguda

• HDL-C

  high-density lipoprotein cholesterol

• HFA

  Heart Failure Association

• HR

• IABP

  intra-aortic balloon pump

• ICCU

  intensive cardiac care unit

• ICD

  implantable cardioverter defibrillator

• IMPROVE-IT

  Improved Reduction of Outcomes: Vytorin Efficacy International Trial

• IRA

• IU

• i.v.

• LBBB

• LDL-C

  low-density lipoprotein cholesterol

• LGE

  late gadolinium enhancement

• LV

  left ventricle/ventricular

• LVAD

  Left ventricular assist device

• LVEF

  left ventricular ejection fraction

• MACE

  major adverse cardiac event

• MATRIX

  Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX

• METOCARD- CNIC

  Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction

• MI

• MINOCA

  myocardial infarction with non-obstructive coronary arteries

• MRA

  mineralocorticoid receptor antagonist

• MVO

  microvascular obstruction

• NORSTENT

• NSTEMI

  non-ST-segment elevation myocardial infarction

• NT-proBNP

  N-terminal pro B-type natriuretic peptide

• OASIS-6

  Organization for the Assessment of Strategies for Ischemic Syndromes

• o.d.

• PAMI-II

  Second Primary Angioplasty in Myocardial Infarction

• PaO₂

  partial pressure of oxygen

• PCI

  percutaneous coronary intervention

• PCSK9

  proprotein convertase subtilisin/kexin type 9

• PEGASUS- TIMI 54

  Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54

• PET

  positron emission tomography

• PIONEER AF-PCI

  Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects with Atrial Fibrillation who Undergo Percutaneous Coronary Intervention

• p.o.

• PPI

• PRAMI

  Preventive Angioplasty in Acute Myocardial Infarction

• PRODIGY

  PROlonging Dual Antiplatelet Treatment After Grading stent-induced Intimal hyperplasia studY

• RBBB

  right bundle branch block

• REMINDER

  A Double-Blind, Randomized, Placebo-Controlled Trial Evaluating The Safety And Efficacy Of Early Treatment With Eplerenone In Patients With Acute Myocardial Infarction

• RIFLE- STEACS

  Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome

• RIVAL

  Radial Versus Femoral Access for Coronary intervention

• RV

  right ventricle/ventricular

• SaO₂

  arterial oxygen saturation

• SBP

• s.c.

• SGLT2

  sodium-glucose co-transporter-2

• SPECT

  single-photon emission computed tomography

• STEMI

  ST-segment elevation myocardial infarction

• STREAM

  STrategic Reperfusion Early After Myocardial infarction

• TIMI

  Thrombolysis In Myocardial Infarction

• TNK-tPA

  Tenecteplase tissue plasminogen activator

• TOTAL

  Trial of Routine Aspiration Thrombectomy with PCI versus PCI Alone in Patients with STEMI

• tPA

  tissue plasminogen activator

• UFH

• VALIANT

  VALsartan In Acute myocardial iNfarcTion

• VF

• VT

• 24/7

  24 h a day, seven days a week

1. Preamble

Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in selecting the best management strategies for an individual patient with a given condition. Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.

A great number of guidelines have been issued in recent years by the European Society of Cardiology (ESC), as well as by other societies and organisations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESC website (https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Guidelines-development/Writing-ESC-Guidelines). ESC Guidelines represent the official position of the ESC on a given topic and are regularly updated.

Members of this Task Force were selected by the ESC, including representation from its relevant ESC sub-specialty groups, in order to represent professionals involved with the medical care of patients with this pathology. Selected experts in the field undertook a comprehensive review of the published evidence for management of a given condition according to ESC Committee for Practice Guidelines (CPG) policy. A critical evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk–benefit ratio. The level of evidence and the strength of the recommendation of particular management options were weighed and graded according to predefined scales, as outlined in Tables 1 and 2.

Table 1

Classes of recommendations

Table 1

Classes of recommendations

Table 2

Levels of evidence

Table 2

Levels of evidence

The experts of the writing and reviewing panels provided declaration of interest forms for all relationships that might be perceived as real or potential sources of conflicts of interest. These forms were compiled into one file and can be found on the ESC website (http://www.escardio.org/guidelines). Any changes in declarations of interest that arise during the writing period were notified to the ESC and updated. The Task Force received its entire financial support from the ESC without any involvement from the healthcare industry.

The ESC CPG supervises and coordinates the preparation of new ESC Guidelines. The Committee is also responsible for the endorsement process of these Guidelines. The ESC Guidelines undergo extensive review by the CPG and external experts. After appropriate revisions the Guidelines are approved by all the experts involved in the Task Force. The finalized document is approved by the CPG for publication in the European Heart Journal. The Guidelines were developed after careful consideration of the scientific and medical knowledge and the evidence available at the time of their dating.

The task of developing ESC Guidelines also includes the creation of educational tools and implementation programmes for the recommendations including condensed pocket guideline versions, summary slides, booklets with essential messages, summary cards for non-specialists and an electronic version for digital applications (smartphones, etc.). These versions are abridged and thus, if needed, one should always refer to the full text version, which is freely available via the ESC website and hosted on the EHJ website. The National Societies of the ESC are encouraged to endorse, translate and implement all ESC Guidelines. Implementation programmes are needed because it has been shown that the outcome of disease may be favourably influenced by the thorough application of clinical recommendations.

Surveys and registries are needed to verify that real-life daily practice is in keeping with what is recommended in the guidelines, thus completing the loop between clinical research, writing of guidelines, disseminating them and implementing them into clinical practice.

Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies. However, the ESC Guidelines do not override in any way whatsoever the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient or the patient's caregiver where appropriate and/or necessary. It is also the health professional's responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.

2. Introduction

Updates on the management of patients presenting with ST-segment elevation myocardial infarction (STEMI) should be based on sound evidence, derived from well-conducted clinical trials whenever possible, or motivated expert opinion when needed. It must be recognized that, even when excellent clinical trials have been undertaken, the results are open to interpretation and treatments may need to be adapted to take account of clinical circumstances and resources.

The present Task Force has made an important effort to be as aligned as possible with the other ESC Guidelines ^1–6 and consensus documents, including the simultaneously published update on dual antiplatelet therapy (DAPT), ⁷ for consistency in the ESC Guidelines strategy. The levels of evidence and the strengths of recommendation of particular treatment options were weighed and graded according to pre-defined scales, as outlined in Tables 1 and 2. Despite recommendations with a level of evidence being based on expert opinion, this Task Force decided to add references to guide the reader regarding data that were taken into consideration for these decisions in some cases.

2.1 Definition of acute myocardial infarction

The term acute myocardial infarction (AMI) should be used when there is evidence of myocardial injury (defined as an elevation of cardiac troponin values with at least one value above the 99th percentile upper reference limit) with necrosis in a clinical setting consistent with myocardial ischaemia. ⁸ For the sake of immediate treatment strategies such as reperfusion therapy, it is usual practice to designate patients with persistent chest discomfort or other symptoms suggestive of ischaemia and ST-segment elevation in at least two contiguous leads as STEMI. In contrast, patients without ST-segment elevation at presentation are usually designated as having a non-ST-segment elevation myocardial infarction (MI) (NSTEMI) and separate guidelines have recently been developed for these. ² Some patients with MI develop Q-waves (Q-wave MI), but many do not (non-Q-wave MI).

In addition to these categories, MI is classified into various types, based on pathological, clinical, and prognostic differences, along with different treatment strategies (see the Third Universal Definition of MI document, ⁸ which will be updated in 2018). Despite the fact that the majority of STEMI patients are classified as a type 1 MI (with evidence of a coronary thrombus), some STEMIs fall into other MI types. ⁸ MI, even presenting as STEMI, also occurs in the absence of obstructive coronary artery disease (CAD) on angiography. ^9–12 This type of MI is termed 'myocardial infarction with non-obstructive coronary arteries' (MINOCA) and is discussed in Chapter 9 of this document.

2.2 Epidemiology of ST-segment elevation myocardial infarction

Worldwide, ischaemic heart disease is the single most common cause of death and its frequency is increasing. However, in Europe, there has been an overall trend for a reduction in ischaemic heart disease mortality over the past three decades. ¹³ Ischaemic heart disease now accounts for almost 1.8 million annual deaths, or 20% of all deaths in Europe, although with large variations between countries. ¹⁴

The relative incidences of STEMI and NSTEMI are decreasing and increasing, respectively. ^{15 , 16} Probably the most comprehensive European STEMI registry is found in Sweden, where the incidence rate of STEMI was 58 per 100 000 per year in 2015. ¹⁷ In other European countries, the incidence rate ranged from 43 to 144 per 100 000 per year. ¹⁸ Similarly, the reported adjusted incidence rates from the USA decreased from 133 per 100 000 in 1999 to 50 per 100 000 in 2008, whereas the incidence of NSTEMI remained constant or increased slightly. ¹⁹ There is a consistent pattern for STEMI to be relatively more common in younger than in older people, and more common in men than in women. ^{17 , 20}

The mortality in STEMI patients is influenced by many factors, among them advanced age, Killip class, time delay to treatment, presence of emergency medical system (EMS)-based STEMI networks, treatment strategy, history of MI, diabetes mellitus, renal failure, number of diseased coronary arteries, and left ventricular ejection fraction (LVEF). Several recent studies have highlighted a fall in acute and long-term mortality following STEMI in parallel with greater use of reperfusion therapy, primary percutaneous coronary intervention (PCI), modern antithrombotic therapy, and secondary prevention. ^{14 , 21 , 22} Nevertheless, mortality remains substantial; the in-hospital mortality of unselected patients with STEMI in the national registries of the ESC countries varies between 4 and 12%, ²³ while reported 1-year mortality among STEMI patients in angiography registries is approximately 10%. ^{24 , 25}

Although ischaemic heart disease develops on average 7–10 years later in women compared with men, MI remains a leading cause of death in women. Acute coronary syndrome (ACS) occurs three to four times more often in men than in women below the age of 60 years, but after the age of 75, women represent the majority of patients. ²⁶ Women tend to present more often with atypical symptoms, up to 30% in some registries, ²⁷ and tend to present later than men. ^{28 , 29} It is therefore important to maintain a high degree of awareness for MI in women with potential symptoms of ischaemia. Women also have a higher risk of bleeding complications with PCI. There is an ongoing debate regarding whether outcomes are poorer in women, with several studies indicating that a poorer outcome is related to older age and more comorbidities among women suffering MI. ^{26 , 30 , 31} Some studies have indicated that women tend to undergo fewer interventions than men and receive reperfusion therapy less frequently. ^{26 , 32 , 33} These guidelines aim to highlight the fact that women and men receive equal benefit from a reperfusion strategy and STEMI-related therapy, and that both genders must be managed in a similar fashion.

3. What is new in the 2017 version?

Figure 1

What is new in 2017 STEMI Guidelines. BMS = bare metal stent; DES = drug eluting stent; IRA = infarct related artery; i.v. = intravenous; LDL = low-density lipoprotein; PCI = percutaneous coronary intervention; SaO2 = arterial oxygen saturation; STEMI = ST-elevation myocardial infarction; TNK-tPA = Tenecteplase tissue plasminogen activator. For explanation of trial names, see list of.

^aOnly for experienced radial operators.

^bBefore hospital discharge (either immediate or staged).

^cRoutine thrombus aspiration (bailout in certain cases may be considered).

^dIn 2012 early discharge was considered after 72h, in 2017 early discharge is 48–72h.

^eIf symptoms or haemodynamic instability IRA should be opened regardless time from symptoms onset.

In left and mid panels, below each recommendation, the most representative trial (acronym and reference) driving the indication is mentioned.

Figure 1

What is new in 2017 STEMI Guidelines. BMS = bare metal stent; DES = drug eluting stent; IRA = infarct related artery; i.v. = intravenous; LDL = low-density lipoprotein; PCI = percutaneous coronary intervention; SaO2 = arterial oxygen saturation; STEMI = ST-elevation myocardial infarction; TNK-tPA = Tenecteplase tissue plasminogen activator. For explanation of trial names, see list of.

^aOnly for experienced radial operators.

^bBefore hospital discharge (either immediate or staged).

^cRoutine thrombus aspiration (bailout in certain cases may be considered).

^dIn 2012 early discharge was considered after 72h, in 2017 early discharge is 48–72h.

^eIf symptoms or haemodynamic instability IRA should be opened regardless time from symptoms onset.

In left and mid panels, below each recommendation, the most representative trial (acronym and reference) driving the indication is mentioned.

4. Emergency care

4.1 Initial diagnosis

Management—including diagnosis and treatment—of STEMI starts from the point of first medical contact (FMC, defined in Table 4). It is recommended that a regional reperfusion strategy should be established to maximize efficiency.

A working diagnosis of STEMI (called the 'STEMI diagnosis' throughout this document) must first be made. This is usually based on symptoms consistent with myocardial ischaemia (i.e. persistent chest pain) and signs [i.e. 12-lead electrocardiogram (ECG)]. Important clues are a history of CAD and radiation of pain to the neck, lower jaw, or left arm. Some patients present with less-typical symptoms such as shortness of breath, nausea/vomiting, fatigue, palpitations, or syncope. ³⁴ A reduction in chest pain after nitroglycerin (glyceryl trinitrate) administration can be misleading and is not recommended as a diagnostic manoeuvre. ³⁵ In cases of symptom relief after nitroglycerin administration, another 12-lead ECG must be obtained. A complete normalization of the ST-segment elevation after nitroglycerin administration, along with complete relief of symptoms, is suggestive of coronary spasm, with or without associated MI. In these cases, an early coronary angiography (within 24 h) is recommended. In cases of recurrent episodes of ST-segment elevation or chest pain, immediate angiography is required.

It is recommended to initiate ECG monitoring as soon as possible in all patients with suspected STEMI in order to detect life-threatening arrhythmias and allow prompt defibrillation if indicated. When a STEMI is suspected, a 12-lead ECG must be acquired and interpreted as soon as possible at the time of FMC to facilitate early STEMI diagnosis and triage. ^36–40

In patients with a clinical suspicion of myocardial ischaemia and ST-segment elevation, reperfusion therapy needs to be initiated as soon as possible. ⁴¹ If the ECG is equivocal or does not show evidence to support the clinical suspicion of MI, ECGs should be repeated and, when possible compared with previous recordings. If interpretation of pre-hospital ECG is not possible on-site, field transmission of the ECG is recommended. ⁴²

ECG criteria are based on changes of electrical currents of the heart (measured in millivolts). Standard calibration of the ECG is 10mm/mV. Therefore 0.1 mV equals to 1 mm square on the vertical axis. For simplicity, in this document ECG deviations are expressed in mm following the standard calibration.

In the proper clinical context, ST-segment elevation (measured at the J-point) is considered suggestive of ongoing coronary artery acute occlusion in the following cases: at least two contiguous leads with ST-segment elevation ≥ 2.5 mm in men < 40 years, ≥2 mm in men ≥ 40 years, or ≥ 1.5 mm in women in leads V₂–V₃ and/or ≥ 1 mm in the other leads [in the absence of left ventricular (LV) hypertrophy or left bundle branch block LBBB)]. ⁸ In patients with inferior MI, it is recommended to record right precordial leads (V₃R and V₄R) seeking ST-segment elevation, to identify concomitant right ventricular (RV) infarction. ^{8 , 43} Likewise, ST-segment depression in leads V₁–V₃ suggests myocardial ischaemia, especially when the terminal T-wave is positive (ST-segment elevation equivalent), and confirmation by concomitant ST-segment elevation ≥ 0.5 mm recorded in leads V₇–V₉ should be considered as a means to identify posterior MI. ⁸ The presence of a Q-wave on the ECG should not necessarily change the reperfusion strategy decision.

Recommendations for initial diagnosis

ECG = electrocardiogram; FMC = first medical contact; MI = myocardial infarction; RV = right ventricle; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

Recommendations for initial diagnosis

ECG = electrocardiogram; FMC = first medical contact; MI = myocardial infarction; RV = right ventricle; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

The ECG diagnosis may be more difficult in some cases, which nevertheless deserve prompt management and triage. Among these:

Bundle branch block. In the presence of LBBB, the ECG diagnosis of AMI is difficult but often possible if marked ST-segment abnormalities are present. Somewhat complex algorithms have been offered to assist the diagnosis, ^{50 , 51} but they do not provide diagnostic certainty. ⁵² The presence of concordant ST-segment elevation (i.e. in leads with positive QRS deflections) appears to be one of the best indicators of ongoing MI with an occluded infarct artery. ⁵³ Patients with a clinical suspicion of ongoing myocardial ischaemia and LBBB should be managed in a way similar to STEMI patients, regardless of whether the LBBB is previously known. It is important to remark that the presence of a (presumed) new LBBB does not predict an MI per se. ⁵⁴

Patients with MI and right bundle branch block (RBBB) have a poor prognosis. ⁵⁵ It may be difficult to detect transmural ischaemia in patients with chest pain and RBBB. ⁵⁵ Therefore, a primary PCI strategy (emergent coronary angiography and PCI if indicated) should be considered when persistent ischaemic symptoms occur in the presence of RBBB.

Ventricular pacing. Pacemaker rhythm may also prevent interpretation of ST-segment changes and may require urgent angiography to confirm diagnosis and initiate therapy. Reprogramming the pacemaker—allowing an evaluation of ECG changes during intrinsic heart rhythm—may be considered in patients who are not dependent on ventricular pacing, without delaying invasive investigation. ^{56 , 57}

Non-diagnostic ECG. Some patients with an acute coronary occlusion may have an initial ECG without ST-segment elevation, sometimes because they are seen very early after symptom onset (in which case, one should look for hyper-acute T-waves, which may precede ST-segment elevation). It is important to repeat the ECG or monitor for dynamic ST-segment changes. In addition, there is a concern that some patients with acute occlusion of a coronary artery and ongoing MI, such as those with an occluded circumflex coronary artery, ^{58 , 59} acute occlusion of a vein graft, or left main disease, may present without ST-segment elevation and be denied reperfusion therapy, resulting in a larger infarction and worse outcomes. Extending the standard 12-lead ECG with V₇–V₉ leads may identify some of these patients. In any case, suspicion of ongoing myocardial ischaemia is an indication for a primary PCI strategy even in patients without diagnostic ST-segment elevation. ^{8 , 38 , 46–49} Table 3 lists the atypical ECG presentations that should prompt a primary PCI strategy in patients with ongoing symptoms consistent with myocardial ischaemia.

Table 3

Atypical electrocardiographic presentations that should prompt a primary percutaneous coronary intervention strategy in patients with ongoing symptoms consistent with myocardial ischaemia

ECG = electrocardiogram; LBBB = left bundle branch block; RBBB = right bundle branch block; RV = right ventricular; STEMI = ST-segment elevation myocardial infarction.

Table 3

Atypical electrocardiographic presentations that should prompt a primary percutaneous coronary intervention strategy in patients with ongoing symptoms consistent with myocardial ischaemia

ECG = electrocardiogram; LBBB = left bundle branch block; RBBB = right bundle branch block; RV = right ventricular; STEMI = ST-segment elevation myocardial infarction.

Table 4

Definitions of terms related to reperfusion therapy

ECG = electrocardiogram; EMS = emergency medical system; FMC = first medical contact; IRA = infarct-related artery; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

Table 4

Definitions of terms related to reperfusion therapy

ECG = electrocardiogram; EMS = emergency medical system; FMC = first medical contact; IRA = infarct-related artery; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

Isolated posterior MI. In AMI of the inferior and basal portion of the heart, often corresponding to the left circumflex territory, isolated ST-segment depression ≥ 0.5 mm in leads V₁–V₃ represents the dominant finding. These should be managed as a STEMI. The use of additional posterior chest wall leads [elevation V₇–V₉ ≥ 0.5 mm (≥1 mm in men, 40 years old)] is recommended to detect ST-segment elevation consistent with inferior and basal MI.

Left main coronary obstruction. The presence of ST depression ≥ 1 mm in eight or more surface leads (inferolateral ST depression), coupled with ST-segment elevation in aVR and/or V₁, suggests multivessel ischemia or left main coronary artery obstruction, particularly if the patient presents with haemodynamic compromise. ⁶⁰

Blood sampling for serum markers is routinely carried out in the acute phase. This is indicated, but should not delay the reperfusion strategy/treatment.

If in doubt regarding the possibility of acute evolving MI, emergency imaging aids the provision of timely reperfusion therapy to these patients. Recommendations for the use of echocardiography for initial diagnosis are described in section 6.6.2. If echocardiography is not available or if doubts persist after echo, a primary PCI strategy is indicated (including immediate transfer to a PCI centre if the patient is being treated in a non-PCI centre).

In the STEMI emergency setting, there is no role for routine computed tomography (CT). Use of CT should be confined to selected cases where acute aortic dissection or pulmonary embolism is suspected, but CT is not recommended if STEMI diagnosis is likely.

Some non-AMI conditions can present with symptoms and ECG findings similar to STEMI. An emergency coronary angiography is therefore indicated in these cases (Chapter 9 expands on this topic).

4.2 Relief of pain, breathlessness, and anxiety

Relief of pain is of paramount importance, not only for comfort reasons but because the pain is associated with sympathetic activation, which causes vasoconstriction and increases the workload of the heart. Titrated intravenous (i.v.) opioids (e.g. morphine) are the analgesics most commonly used in this context. However, morphine use is associated with a slower uptake, delayed onset of action, and diminished effects of oral antiplatelet agents (i.e. clopidogrel, ticagrelor, and prasugrel), which may lead to early treatment failure in susceptible individuals. ^61–63

Relief of hypoxaemia and symptoms

i.v. = intravenous; PaO₂ = partial pressure of oxygen; SaO₂ = arterial oxygen saturation.

a

Class of recommendation.

b

Level of evidence.

Relief of hypoxaemia and symptoms

i.v. = intravenous; PaO₂ = partial pressure of oxygen; SaO₂ = arterial oxygen saturation.

a

Class of recommendation.

b

Level of evidence.

Oxygen is indicated in hypoxic patients with arterial oxygen saturation (SaO₂) < 90%. There is some evidence suggesting that hyperoxia may be harmful in patients with uncomplicated MI, presumably due to increased myocardial injury. ^64–67 Thus, routine oxygen is not recommended when SaO₂ is ≥ 90%.

Anxiety is a natural response to the pain and the circumstances surrounding an MI. Reassurance of patients and those closely associated with them is of great importance.

A mild tranquillizer (usually a benzodiazepine) should be considered in anxious patients.

4.3 Cardiac arrest

Many deaths occur very early after STEMI onset due to ventricular fibrillation (VF). ⁶⁸ As this arrhythmia frequently occurs at an early stage, these deaths usually happen out of hospital. It is indicated that all medical and paramedical personnel caring for patients with suspected MI have access to defibrillation equipment and are trained in cardiac life support, and that, at the point of FMC, ECG monitoring must be implemented immediately for all patients with suspected MI.

Patients with chest pain suggestive of MI should be directed through public awareness programmes to contact the EMS and wait to be transferred to the hospital by the EMS.

In patients following cardiac arrest and ST-segment elevation on the ECG, primary PCI is the strategy of choice. ^69–74

Given the high prevalence of coronary occlusions and the potential difficulties in interpreting the ECG in patients after cardiac arrest, urgent angiography (within 2 h) ² should be considered in survivors of cardiac arrest, including unresponsive survivors, when there is a high index of suspicion of ongoing infarction (such as the presence of chest pain before arrest, a history of established CAD, and abnormal or uncertain ECG results). ^{73 , 74} However, in patients without ST-segment elevation, a quick evaluation at the emergency department or intensive cardiac care unit (ICCU) to exclude non-coronary causes (cerebrovascular event, respiratory failure, non-cardiogenic shock, pulmonary embolism, and intoxication), and to perform urgent echocardiography, is reasonable. The decision to perform urgent coronary angiography and PCI if indicated should also take into account factors associated with poor neurological outcome. Unfavourable pre-hospital settings indicating a remote likelihood for neurological recovery [i.e. unwitnessed cardiac arrest, late arrival of a pre-hospital team without lay basic life support (>10 min), presence of an initial non-shockable rhythm, or more than 20 min of advanced life support without return to spontaneous circulation] ⁷⁵ should be taken strongly into consideration to argue against an invasive coronary strategy. ⁷³

Unconscious patients admitted to critical care units after out-of-hospital cardiac arrest are at high risk for death, and neurologic deficits are common among those who survive. ⁷⁶ Targeted temperature management (also called therapeutic hypothermia), aiming for a constant temperature between 32 and 36 °C for at least 24 h, is indicated in patients who remain unconscious after resuscitation from cardiac arrest (of presumed cardiac cause). ^{73 , 77–82} However, hypothermia conditions are associated with slow uptake, delayed onset of action, and diminished effects of oral antiplatelet agents (i.e. clopidogrel, ticagrelor, and prasugrel). Moreover, metabolic conversion of clopidogrel in the liver may be reduced in hypothermia conditions. ⁸³ Cooling should not delay primary PCI and can be started in parallel in the catheterization laboratory. Close attention to anticoagulation needs to be paid in patients reaching low temperatures. ⁸⁴

Prevention and improved treatment of out-of-hospital cardiac arrest is crucial to reduce the mortality related to CAD. For a more detailed discussion of these issues, refer to the recent European Resuscitation Council Guidelines for resuscitation. ⁷⁴

24/7 = 24 h a day, 7 days a week; ECG = electrocardiogram; EMS = emergency medical system; i.v. = intravenous; MI = myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

c

Targeted temperature management refers to active methods (i.e. cooling catheters, cooling blankets, and application of ice applied around the body) to achieve and maintain a constant specific body temperature between 32 and 36 °C in a person for a specific duration of time (most commonly used ≥ 24 h).

24/7 = 24 h a day, 7 days a week; ECG = electrocardiogram; EMS = emergency medical system; i.v. = intravenous; MI = myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

c

Targeted temperature management refers to active methods (i.e. cooling catheters, cooling blankets, and application of ice applied around the body) to achieve and maintain a constant specific body temperature between 32 and 36 °C in a person for a specific duration of time (most commonly used ≥ 24 h).

4.4 Pre-hospital logistics of care

4.4.1 Delays

Treatment delays are the most easily audited index of quality of care in STEMI; they should be recorded in every system providing care to STEMI patients and be reviewed regularly, to ensure that simple quality of care indicators are met and maintained over time (see Chapter 10). If projected target times are not met, then interventions are needed to improve performance of the system. Components of the ischaemic time, delays of initial management, and selection of reperfusion strategy are shown in Figure 2.

Figure 2

Modes of patient presentation, components of ischaemia time and flowchart for reperfusion strategy selection. EMS = Emergency Medical System; FMC = First Medical Contact; PCI = Percutaneous Coronary Intervention; STEMI = ST-segment elevation myocardial infarction.

The recommended mode of patient presentation is by alerting the EMS (call national emergency number: 112 or similar number according to region). When STEMI diagnosis is made in the out-of-hospital setting (via EMS) or in a non-PCI centre, the decision for choosing reperfusion strategy is based on the estimated time from STEMI diagnosis to PCI-mediated reperfusion (wire crossing). System delay for patients alerting the EMS starts at the time of phone alert, although FMC occurs when EMS arrives to the scene (see Table 4). ´denotes minutes. ^aPatients with fibrinolysis should be transferred to a PCI centre immediately after administration of the lytic bolus.

Figure 2

Modes of patient presentation, components of ischaemia time and flowchart for reperfusion strategy selection. EMS = Emergency Medical System; FMC = First Medical Contact; PCI = Percutaneous Coronary Intervention; STEMI = ST-segment elevation myocardial infarction.

The recommended mode of patient presentation is by alerting the EMS (call national emergency number: 112 or similar number according to region). When STEMI diagnosis is made in the out-of-hospital setting (via EMS) or in a non-PCI centre, the decision for choosing reperfusion strategy is based on the estimated time from STEMI diagnosis to PCI-mediated reperfusion (wire crossing). System delay for patients alerting the EMS starts at the time of phone alert, although FMC occurs when EMS arrives to the scene (see Table 4). ´denotes minutes. ^aPatients with fibrinolysis should be transferred to a PCI centre immediately after administration of the lytic bolus.

To minimize patient delay, it is recommended to increase public awareness of how to recognize common symptoms of AMI and to call the emergency services. All components of the system delay represent the quality of care and it is recommended to measure them as quality indicators (see Chapter 10).

In hospitals and EMS participating in the care of STEMI patients, the goal is to reduce the delay between FMC and STEMI diagnosis to ≤ 10 min. STEMI diagnosis refers to the time when the ECG is interpreted as ST-segment elevation or equivalent and it is the time zero to guide appropriate therapy.

System delay is more readily modifiable by organizational measures than is patient delay, and it is a predictor of outcomes. ⁸⁷

When STEMI diagnosis is made in the pre-hospital setting (EMS), immediate activation of the catheterization laboratory not only reduces treatment delays but may also reduce patient mortality. ^88–91 When a STEMI diagnosis is made by the EMS in the pre-hospital setting and the patient is triaged for a primary PCI strategy, it is indicated to bypass the emergency department and bring the patient straight to the catheterization laboratory. Bypassing the emergency department is associated with a 20 min saving in the time from FMC to wire crossing. ⁹² For patients presenting in a non-PCI centre, door-in to door-out time, defined as the duration between arrival of the patient at the hospital to discharge of the patient in an ambulance en route to the PCI centre, is a new clinical performance measure, and ≤30 min is recommended to expedite reperfusion care. ⁹³

4.4.2 Emergency medical system

An EMS with an easily recalled and well publicized unique medical dispatching number (112 for most medical emergencies across Europe) is important to speed up activation. Parallel circuits for referral and transport of patients with a STEMI that bypass the EMS should be avoided. The ambulance system has a critical role in the early management of STEMI patients and it is not only a mode of transport but also a system to enhance early initial diagnosis, triage, and treatment. ^{87 , 94}

It is indicated that all ambulances in the EMS are equipped with ECG recorders, defibrillators, and at least one person trained in advanced life support. The quality of the care provided depends on the training of the staff involved. It is indicated that all ambulance personnel are trained to recognize the symptoms of an AMI, administer oxygen when appropriate, relieve pain, and provide basic life support. ⁹⁵ Ambulance staff should be able to record an ECG for diagnostic purposes and either interpret or transmit it, so that it can be reviewed by experienced staff in a coronary care unit (CCU)/ICCU or elsewhere and establish a STEMI diagnosis. Paramedics trained to administer fibrinolytics do so safely and effectively. ⁹⁶ As pre-hospital fibrinolysis is indicated in patients presenting early when anticipated STEMI diagnosis to PCI-mediated reperfusion time is > 120 min, ^97–99 ongoing training of paramedics to undertake these functions is recommended, even in the current setting of primary PCI.

4.4.3 Organization of ST-segment elevation myocardial infarction treatment in networks

Optimal treatment of STEMI should be based on the implementation of networks between hospitals ('hub' and 'spoke') with various levels of technology, linked by a prioritized and efficient ambulance service. The goal of these networks is to provide optimal care while minimizing delays, thereby improving clinical outcomes. Cardiologists should actively collaborate with all stakeholders, particularly emergency physicians, in establishing such networks. The main features of such a network are:

• ▪ Clear definition of geographic areas of responsibility.

• ▪ Shared written protocols, based on risk stratification and transportation by a trained physician, nurse, or paramedic staff in appropriately equipped ambulances or helicopters.

• ▪ Pre-hospital triage of STEMI patients to the appropriate institution, bypassing non-PCI hospitals or hospitals without a 24 h a day, 7 days a week (24/7) primary PCI programme.

• ▪ On arrival at the appropriate hospital, the patient should immediately be taken to the catheterization laboratory, bypassing the emergency department.

• ▪ Patients presenting to a non-PCI-capable hospital and awaiting transportation for primary or rescue PCI must be attended in an appropriately monitored and staffed area.

• ▪ If the diagnosis of STEMI has not been made by the ambulance crew and the ambulance arrives at a non-PCI-capable hospital, the ambulance should await the diagnosis and, if a STEMI diagnosis is made, should continue to a PCI-capable hospital.

To maximize staff experience, primary PCI centres should perform the procedure systematically on a 24/7 basis for all STEMI patients. Other models, although not ideal, may include weekly or daily rotation of primary PCI centres or multiple primary PCI centres in the same region. Hospitals that cannot offer a 24/7 service for primary PCI should be allowed to perform primary PCI in patients already admitted for another reason who develop STEMI during their hospital stay. However, these hospitals should be discouraged from initiating a service limited to daytime- or within-hours primary PCI, as this may generate confusion with the EMS operators and may affect the STEMI diagnosis-to-reperfusion time and the quality of intervention of focused 24/7 true primary PCI centres. Therefore, it is indicated that the EMS transports STEMI patients to hospitals with an established interventional cardiology programme available 24/7, if necessary bypassing a non-PCI-capable hospital (if the transfer time is within the recommended time-windows for primary PCI; see Figure 3).

Figure 3

Maximum target times according to reperfusion strategy selection in patients presenting via EMS or in a non-PCI centre. ECG = electrocardiogram; PCI = Percutaneous Coronary Intervention; STEMI = ST-segment elevation myocardial infarction. STEMI diagnosis is the time 0 for the strategy clock. The decision for choosing reperfusion strategy in patients presenting via EMS (out-of-hospital setting) or in a non-PCI centre is based on the estimated time from STEMI diagnosis to PCI-mediated reperfusion. Target times from STEMI diagnosis represent the maximum time to do specific interventions.

^aif fibrinolysis is contra-indicated, direct for primary PCI strategy regardless of time to PCI.

^b10 min is the maximum target delay time from STEMI diagnosis to fibrinolytic bolus administration, however, it should be given as soon as possible after STEMI diagnosis (after ruling out contra-indications).

Figure 3

Maximum target times according to reperfusion strategy selection in patients presenting via EMS or in a non-PCI centre. ECG = electrocardiogram; PCI = Percutaneous Coronary Intervention; STEMI = ST-segment elevation myocardial infarction. STEMI diagnosis is the time 0 for the strategy clock. The decision for choosing reperfusion strategy in patients presenting via EMS (out-of-hospital setting) or in a non-PCI centre is based on the estimated time from STEMI diagnosis to PCI-mediated reperfusion. Target times from STEMI diagnosis represent the maximum time to do specific interventions.

^aif fibrinolysis is contra-indicated, direct for primary PCI strategy regardless of time to PCI.

^b10 min is the maximum target delay time from STEMI diagnosis to fibrinolytic bolus administration, however, it should be given as soon as possible after STEMI diagnosis (after ruling out contra-indications).

Geographic areas where the expected transfer time to the primary PCI centre makes it impossible to achieve the maximal allowable delays indicated in the recommendations (Figure 2) should develop systems for rapid fibrinolysis, at the place of STEMI diagnosis, with subsequent immediate transfer to primary PCI centres. Such networks increase the proportion of patients receiving reperfusion with the shortest possible treatment delay. ^100–102 The quality of care, time delays, and patient outcomes should be measured and compared at regular intervals for improvement.

4.4.3.1. General practitioners

In some countries, general practitioners play a role in the early care of patients with AMI and are often the first to be contacted by the patients.

If general practitioners respond quickly they can be very effective, as they usually know the patient and can perform and interpret the ECG. Their first task after the STEMI diagnosis should be to alert the EMS. In addition, they can administer opioids and antithrombotic drugs (including fibrinolytics, if that management strategy is indicated), and can undertake defibrillation if needed. However, in most settings, consultation with a general practitioner—instead of a direct call to the EMS—will increase pre-hospital delay. Therefore, in general, the public should be educated to call the EMS rather than the primary care physician for symptoms suggestive of MI.

Logistics of pre-hospital care

24/7 = 24 h a day, 7 days a week; CCU = coronary care unit; ECG = electrocardiogram; EMS = emergency medical system; ICCU = intensive cardiac care unit; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

Logistics of pre-hospital care

24/7 = 24 h a day, 7 days a week; CCU = coronary care unit; ECG = electrocardiogram; EMS = emergency medical system; ICCU = intensive cardiac care unit; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

5. Reperfusion therapy

5.1 Selection of reperfusion strategies

Table 4 lists the definitions of terms relating to reperfusion therapy.

Primary PCI is the preferred reperfusion strategy in patients with STEMI within 12 h of symptom onset, provided it can be performed expeditiously (i.e. 120 min from STEMI diagnosis, Figures 2 and 3) by an experienced team. An experienced team includes not only interventional cardiologists but also skilled support staff. Lower mortality rates among patients undergoing primary PCI are observed in centres with a high volume of PCI procedures. ¹¹¹ Real-life data confirm that primary PCI is performed faster and results in lower mortality if performed in high-volume centres. ¹¹² Randomized clinical trials in high-volume, experienced centres have repeatedly shown that, if delay to treatment is similar, primary PCI is superior to fibrinolysis in reducing mortality, reinfarction, or stroke. ^113–116 However, in some circumstances, primary PCI is not an immediate option and fibrinolysis could be initiated expeditiously. The extent to which the PCI-related time delay diminishes the advantages of PCI over fibrinolysis has been widely debated. Because no specifically designed study has addressed this issue, caution is needed when interpreting available data from post hoc analyses. A PCI-related time delay potentially mitigating the benefits of PCI has been calculated as 60 min ¹¹⁷ , 110 min, ¹¹⁸ and 120 min ¹¹⁹ in different studies. Registry data estimated this time limit as 114 min for in-hospital patients ¹⁰⁷ and 120 min in patients presenting in a non-PCI centre. ¹²⁰ All these data are old and patients undergoing fibrinolysis did not undergo routine early angiography, which improves outcomes in patients receiving fibrinolysis. The recent STrategic Reperfusion Early After Myocardial infarction (STREAM) trial randomized early STEMI presenters without the possibility of immediate PCI to immediate fibrinolysis (followed by routine early angiography) or transfer to primary PCI. ¹²¹ The median PCI-related delay in this trial was 78 min, and there were no differences in clinical outcomes. This Task Force recognizes the lack of contemporaneous data to set the limit to choose PCI over fibrinolysis. For simplicity, an absolute time from STEMI diagnosis to PCI-mediated reperfusion [i.e. wire crossing of the infarct-related artery (IRA)] rather than a relative PCI-related delay over fibrinolysis has been chosen. This limit is set to 120 min. Given the maximum limit of 10 min from STEMI diagnosis to bolus of fibrinolytics (see below), the 120 min absolute time would correspond to a PCI-related delay in the range of 110–120 min, being in the range of the times identified in old studies and registries as the limit delay to choose PCI. ^{107 , 117–120}

If the reperfusion strategy is fibrinolysis, the goal is to inject the bolus of fibrinolytics within 10 min from STEMI diagnosis. This time is selected based on the median time from randomization to bolus recorded in the STREAM trial, which was 9 min. ¹²¹ In previous ESC STEMI guidelines, ¹²² the target time was 30 min, but this was calculated from FMC (as opposed to STEMI diagnosis). STEMI diagnosis should occur within 10 min from FMC.

Figure 3 summarizes target times for patients presenting in the pre-hospital setting or in a non-PCI centre.

To shorten time to treatment, fibrinolysis should be administered in the pre-hospital setting if possible ^{98 , 121 , 123} (Figures 2 and 3). Patients should be transferred to a PCI-capable facility as soon as possible after bolus of lytics administration. Rescue PCI is indicated in the case of failed fibrinolysis (i.e. ST-segment resolution < 50% within 60–90 min of fibrinolytic administration), or in the presence of haemodynamic or electrical instability, worsening ischaemia, or persistent chest pain, ^{121 , 124} while a routine early PCI strategy is indicated after successful fibrinolysis (preferably 2–24 h after fibrinolysis) (see section 5.3). ^125–130

Patients with a clinical presentation compatible with AMI and a non-interpretable ST-segment on the ECG, such as those with bundle branch block or ventricular pacing, ^{55 , 131 , 132} should undergo a primary PCI strategy.

There is general agreement that a primary PCI strategy should also be followed for patients with symptoms lasting >12 h in the presence of: (1) ECG evidence of ongoing ischaemia; (2) ongoing or recurrent pain and dynamic ECG changes; and (3) ongoing or recurrent pain, symptoms, and signs of heart failure, shock, or malignant arrhythmias. However, there is no consensus as to whether PCI is also beneficial in patients presenting >12 h from symptom onset in the absence of clinical and/or electrocardiographic evidence of ongoing ischaemia. In asymptomatic patients without persistent symptoms 12–48 h after symptom onset, a small (n = 347) randomized study showed improved myocardial salvage and 4 year survival in patients treated with primary PCI compared with conservative treatment alone. ^{133 , 134} However, in stable patients with persistent occlusion of the IRA 3–28 days after MI, the large (n = 2166) Occluded Artery Trial (OAT) revealed no clinical benefit from routine coronary intervention with medical management, beyond that from medical management alone. ^{135 , 136} A meta-analysis of trials testing whether late recanalization of an occluded IRA is beneficial showed no benefit of reperfusion. ¹³⁷ Therefore, routine PCI of an occluded IRA in asymptomatic patients >48 h after onset of symptoms is not indicated. These patients should be managed like all patients with chronic total occlusion, in which revascularization should be considered in the presence of symptoms or objective evidence of viability/ischaemia in the territory of the occluded artery. ¹

Recommendations for reperfusion therapy

IRA = infarct-related artery; MI, myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

Recommendations for reperfusion therapy

IRA = infarct-related artery; MI, myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

Table 5 summarizes the important time targets in acute STEMI.

Table 5

Summary of important time targets

ECG = electrocardiogram; FMC = first medical contact; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction

a

ECG should be interpreted immediately.

Table 5

Summary of important time targets

ECG = electrocardiogram; FMC = first medical contact; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction

a

ECG should be interpreted immediately.

5.2 Primary percutaneous coronary intervention and adjunctive therapy

5.2.1 Procedural aspects of primary percutaneous coronary intervention

5.2.1.1 Access route

Over recent years, several studies have provided robust evidence in favour of the radial approach as the default access site in ACS patients undergoing primary PCI by experienced radial operators. The Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX (MATRIX) ¹⁴³ trial recruited 8404 ACS patients (48% STEMI) who were randomly allocated to transradial or transfemoral access. Radial access was associated with lower risks of access site bleeding, vascular complications, and need for transfusion. Importantly, there was a significant mortality benefit in patients allocated to the transradial access site, which reinforced previous observations from the Radial Versus Femoral Access for Coronary Intervention (RIVAL) access for coronary intervention trial, ¹⁴⁴ and the Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome (RIFLE-STEACS) trial. ¹⁴⁵ No significant interaction was observed in the MATRIX trial between the type of ACS and treatment benefit, suggesting that the results of this investigation can be extended with confidence to the treatment of patients with STEMI.

5.2.1.2 Stenting in primary percutaneous intervention

Coronary stenting is the technique of choice during primary PCI. Compared with balloon angioplasty alone, stenting with a bare-metal stent (BMS) is associated with a lower risk of reinfarction and target vessel revascularization but is not associated with a reduction in the mortality rate. ^{146 , 147} In primary PCI, drug-eluting stents (DES) reduce the risk of repeated target vessel revascularization compared with BMS. ¹⁴⁸

New-generation DES have shown superior safety and preserved or even improved efficacy compared with first-generation DES, in particular with respect to lower risks of stent thrombosis and recurrent MI. In two recent trials—the Effect of biolimus-eluting stents with biodegradable polymer vs. bare-metal stents on cardiovascular events among patients with AMI (COMFORTABLE AMI) trial ¹⁴⁹ and the Everolimus-Eluting Stents Versus Bare-Metal Stents in ST-Segment Elevation Myocardial Infarction (EXAMINATION) trial ¹⁵⁰ —new-generation DES have been shown to be superior to BMS in patients with AMI, mostly in terms of need for reintervention. In the latter trial, the recently released 5 year follow-up results showed a reduction in all-cause mortality by DES as compared to BMS. ¹⁵¹ In the Norwegian Coronary Stent (NORSTENT) trial, ¹⁵² 9013 patients undergoing PCI (26% with STEMI) were randomized to DES or BMS. There were no differences in the incidence of the primary endpoint (composite of death from any cause or non-fatal spontaneous MI) after a median follow-up of 5 years. However, DES were associated with lower rates of definite stent thrombosis (0.8% vs. 1.2%; P = 0.0498) and of target lesion and any repeat revascularization (16.5% vs. 19.8%; P < 0.001). ¹⁵²

Deferring stenting in primary PCI has been investigated as an option to reduce microvascular obstruction (MVO) and preserve microcirculatory function. Two small studies recently found opposite results in the effect of deferred stenting on cardiac magnetic resonance (CMR) imaging-measured MVO. ^{153 , 154} In the larger DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction – Deferred versus conventional stent implantation in patients with ST-segment elevation myocardial infarction (DANAMI 3-DEFER) trial, ¹⁵⁵ in 1215 STEMI patients, deferred stenting (48 h after the index procedure) had no effect on the primary clinical outcome (composite of all-cause mortality, non-fatal MI, or ischaemia-driven revascularization of non-IRA lesions). Routine deferred stenting was associated with a higher need for target vessel revascularization. Based on these findings, routine use of deferred stenting is not recommended.

5.2.1.3 Thrombus aspiration

A number of small-scale or single-centre studies and one meta-analysis of 11 small trials ¹⁵⁶ suggested that there could be benefits from routine manual thrombus aspiration during primary PCI. Recently, two large (>10 000 and >7000 patients) randomized controlled trials, which were adequately powered to detect superiority of routine manual thrombus aspiration versus conventional PCI, showed no benefit on clinical outcomes of routine aspiration strategy overall. ^157–160 A safety concern emerged in the Trial of Routine Aspiration Thrombectomy with PCI versus PCI Alone in Patients with STEMI (TOTAL) trial (n = 10 732), with an increase in the risk of stroke. ¹⁶¹ In the subgroup with high thrombus burden [TIMI (Thrombolysis in Myocardial Infarction) thrombus grade ≥ 3], thrombus aspiration was associated with fewer cardiovascular deaths [170 (2.5%) vs. 205 (3.1%); hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.65–0.98; P = 0.03] and with more strokes or transient ischaemic attacks [55 (0.9%) vs. 34 (0.5%); odds ratio 1.56, 95% CI 1.02–2.42, P =0.04]. However, the interaction P values were 0.32 and 0.34, respectively. ¹⁶²

In the Taste ¹⁵⁷ and TOTAL trials ¹⁵⁹ , 1–5% of randomized patients crossed over from PCI alone to thrombus aspiration. Based on these data and the results of a recent meta-analysis, ¹⁶² routine thrombus aspiration is not recommended, but in cases of large residual thrombus burden after opening the vessel with a guide wire or a balloon, thrombus aspiration may be considered.

5.2.1.4 Multivessel coronary revascularization

Multivessel disease is common (in approximately 50%) in patients with STEMI. ^{163 , 164} While it is recommended to always treat the IRA, evidence supporting immediate (preventive) revascularization of additional significant coronary stenoses is conflicting. It has been reported that patients with extensive CAD in vessels remote from the IRA have lower rates of ST-segment recovery and an adverse prognosis following primary PCI. ¹⁶³ Data from the US National Cardiovascular Data Registry and New York State's Percutaneous Coronary Interventions Reporting System suggested an increase in adverse events, including mortality, in patients treated with immediate multivessel revascularization versus IRA PCI only, while patients in cardiogenic shock were excluded from the analysis. ^{165 , 166}

Randomized clinical trials addressing this issue have been small (each of them included from 69 to 885 patients). One study allocated 214 STEMI patients with multivessel disease to three arms: IRA angioplasty-only, simultaneous treatment of non-IRA lesions, and staged revascularization of the non-IRA. At a mean follow-up of 2.5 years, patients allocated to IRA angioplasty-only had more major adverse cardiac events (MACE) (i.e. death, reinfarction, rehospitalization for ACS, and repeat coronary revascularization) than the patients treated with other strategies. ¹⁶⁷ After this study, four randomized clinical trials have compared PCI of the IRA only vs. complete revascularization: the Preventive Angioplasty in Acute Myocardial Infarction (PRAMI) trial (n = 465, 23 months follow-up), ¹⁶⁸ the Complete Versus Lesion-Only Primary PCI Trial (CvLPRIT) (n = 296, 12 months follow-up), ¹⁶⁹ the Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3–PRIMULTI) trial (n = 627, 27 months follow-up), ¹⁷⁰ and the Comparison Between FFR Guided Revascularization Versus Conventional Strategy in Acute STEMI Patients With Multivessel disease (Compare-Acute, n = 885, 12 months follow-up) trial. ¹⁷¹ PCI of non-IRA was done either during the index procedure (PRAMI and Compare-Acute), staged during hospital admission (DANAMI-3–PRIMULTI), or any time before discharge (immediate or staged) (CVLPRIT). Indication for PCI in non-IRA was angiography-guided in lesions with ≥50% stenosis (PRAMI), >70% stenosis (CVLPRIT), or fractional flow reserve (FFR)-guided (DANAMI-3–PRIMULTI and Compare-Acute). Primary outcome (composite of different endpoints) was significantly reduced in the complete revascularization group in all four trials. Total mortality was not statistically different in any of the four trials. Repeat revascularization was significantly reduced in the complete revascularization arm in the PRAMI, DANAMI-3–PRIMULTI, and Compare-Acute trials. Non-fatal MI was reduced in the non-IRA PCI group only in PRAMI. The lack of significant treatment effect of non-IRA lesion intervention on death or MI was confirmed by three meta-analyses ^172–174 (none of these meta-analyses included the Compare-Acute trial, and one ¹⁷³ did not include the DANAMI-3–PRIMULTI). Based on these data, revascularization of non-IRA lesions should be considered in STEMI patients with multivessel disease before hospital discharge. As the optimal timing of revascularization (immediate vs. staged) has not been adequately investigated, no recommendation in favour of immediate vs. staged multivessel PCI can be formulated.

5.2.1.5 Intra-aortic balloon pump

The Counterpulsation to Reduce Infarct Size Pre-PCI-Acute Myocardial Infarction (CRISP AMI) trial showed no benefit from a routine intra-aortic balloon pump (IABP) in anterior MI without shock, ¹⁷⁵ but there was increased bleeding, which is consistent with previous data regarding the role of IABP in high-risk STEMI without cardiogenic shock. ¹⁷⁶ In addition, a recent randomized trial showed that IABP did not improve outcomes in MI with cardiogenic shock. ¹⁷⁷ Haemodynamic support in patients with cardiogenic shock is discussed in Chapter 8.

Procedural aspects of the primary percutaneous coronary intervention strategy

CABG = coronary artery bypass graft surgery; DES = drug-eluting stent; IRA = infarct-related artery; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

Procedural aspects of the primary percutaneous coronary intervention strategy

CABG = coronary artery bypass graft surgery; DES = drug-eluting stent; IRA = infarct-related artery; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

5.2.2 Periprocedural pharmacotherapy

5.2.2.1 Platelet inhibition

Patients undergoing primary PCI should receive DAPT, a combination of aspirin and a P2Y₁₂ inhibitor, and a parenteral anticoagulant. Aspirin can be given orally including chewing, or i.v. to ensure complete inhibition of thromboxane A2-dependent platelet aggregation. The oral dose of plain aspirin (non-enteric-coated formulation) should preferably be 150–300 mg. There are few clinical data on the optimal i.v. dosage. Given a 50% oral bioavailability of oral aspirin, a corresponding dose is 75–150 mg. Pharmacological data suggest that this lower dose range avoids inhibition of cyclooxygenase-2-dependent prostacyclin. A recent randomized study showed that a single dose of 250 or 500 mg acetylsalicylic acid i.v. compared to 300 mg orally was associated with a faster and more complete inhibition of thromboxane generation and platelet aggregation at 5 min, with comparable rates of bleeding complications. ¹⁸¹

There is limited evidence with respect to when the P2Y₁₂ inhibitor should be initiated in STEMI patients. The Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery (ATLANTIC) trial ¹⁸² is the only randomized study testing the safety and efficacy of different timings of P2Y₁₂ inhibitor initiation in STEMI. In this trial, patients were randomized to receive ticagrelor either during transfer to a primary PCI centre or immediately before angiography. ¹⁸² The median difference between the two tested loading treatment strategies was only 31 min. This study failed to meet the pre-specified primary endpoint in terms of improved ST-segment elevation resolution or TIMI flow before intervention. Rates of major and minor bleeding events were identical in both treatment arms. While the evidence of a clinical benefit of P2Y₁₂ inhibitor pre-treatment in this setting is lacking, early initiation of a P2Y₁₂ inhibitor while the patient is being transported to a primary PCI centre is common practice in Europe and is consistent with the pharmacokinetic data. Furthermore, early treatment with high-dose clopidogrel was superior to in-catheterization laboratory treatment in observational studies and one small randomized trial. ^183–185 In all, the data suggest that the earliest administration may be preferable to achieve early efficacy, particularly for long delays. However, in cases in which the STEMI diagnosis is not clear, delaying P2Y₁₂ inhibitor loading until the anatomy is known should be considered.

The preferred P2Y₁₂ inhibitors are prasugrel [60 mg loading dose and 10 mg maintenance dose once daily per os (p.o.)] or ticagrelor (180 mg p.o. loading dose and 90 mg maintenance dose twice daily). These drugs have a more rapid onset of action, greater potency, and are superior to clopidogrel in clinical outcomes. ^{186 , 187} Prasugrel is contraindicated in patients with previous stroke/transient ischaemic attack, and its use is generally not recommended in patients aged ≥75 years or in patients with lower body weight (<60 kg) as it was not associated with net clinical benefit in these subsets. In case prasugrel is used in these patients, a reduced dose (5 mg) ¹⁸⁸ is recommended. Ticagrelor may cause transient dyspnoea at the onset of therapy, which is not associated with morphological or functional lung abnormalities, and which rarely leads to permanent discontinuation. ¹⁸⁹ Neither prasugrel nor ticagrelor should be used in patients with a previous haemorrhagic stroke, in patients on oral anticoagulants, or in patients with moderate-to-severe liver disease.

When neither of these agents is available (or if they are contraindicated), clopidogrel 600 mg p.o. should be given instead. ¹⁹⁰ Clopidogrel has not been evaluated against placebo in any large outcomes studies in the setting of primary PCI, but a higher regimen of a 600 mg loading dose/150 mg maintenance dose in the first week was superior to the 300/75 mg regimen in the subset of patients undergoing PCI in the Clopidogrel and aspirin Optimal Dose usage to reduce recurrent events–Seventh organization to assess strategies in ischaemic syndromes (CURRENT-OASIS 7) trial, ¹⁹⁰ and use of high clopidogrel loading doses has been demonstrated to achieve more rapid inhibition of the adenosine diphosphate receptor. All P2Y₁₂ inhibitors should be used with caution in patients at high risk of bleeding or with significant anaemia.

Cangrelor is a potent i.v. reversible P2Y₁₂ inhibitor with a rapid onset and offset of action. It has been assessed in three randomized controlled trials enrolling patients with PCI for stable angina or ACS against clopidogrel loading or placebo. ^191–193 A pooled analysis of these three trials showed that cangrelor reduced periprocedural ischaemic complications at the expense of an increased risk of bleeding. ¹⁹⁴ The fact that no potent P2Y₁₂ inhibitors (prasugrel or ticagrelor) were used in patients with an ACS, and only about 18% of the enrolled patients presented with STEMI, ¹⁹³ limits the applicability of the results to current practice of management of STEMI patients. Nevertheless, cangrelor may be considered in patients not pre-treated with oral P2Y₁₂ receptor inhibitors at the time of PCI or in those who are considered unable to absorb oral agents.

The pre-hospital routine upstream use of glycoprotein (GP) IIb/IIIa inhibitors before primary PCI has not been demonstrated to offer a benefit and increases bleeding risk compared with routine use in the catheterization laboratory. ^{195 , 196} Procedural use of abciximab plus unfractionated heparin (UFH) showed no benefit compared to bivalirudin. ¹⁹⁷ Using GP IIb/IIIa inhibitors as bailout therapy in the event of angiographic evidence of a large thrombus, slow- or no-reflow, and other thrombotic complications is reasonable, although this strategy has not been tested in a randomized trial. Overall, there is no evidence to recommend the routine use of GP IIb/IIIa inhibitors for primary PCI. The intracoronary administration of GP IIb/IIIa inhibitors is not superior to its i.v. use. ¹⁹⁸

5.2.2.2 Anticoagulation

Anticoagulant options for primary PCI include UFH, enoxaparin, and bivalirudin. Use of fondaparinux in the context of primary PCI was associated with potential harm in the Organization for the Assessment of Strategies for Ischemic Syndromes 6 (OASIS 6) trial and is not recommended. ¹⁹⁹

There has been no placebo-controlled trial evaluating UFH in primary PCI, but there is a large body of experience with this agent. Dosage should follow standard recommendations for PCI (i.e. initial bolus 70–100 U/kg). There are no robust data recommending the use of activated clotting time to tailor dose or monitor UFH, and if activated clotting time is used, it should not delay recanalization of the IRA. An i.v. bolus of enoxaparin 0.5 mg/kg was compared with UFH in the randomized open-label Acute myocardial infarction Treated with primary angioplasty and inTravenous enOxaparin or unfractionated heparin to Lower ischaemic and bleeding events at short- and Long-term follow-up (ATOLL) trial, including 910 STEMI patients. ²⁰⁰ The primary composite endpoint of 30 day death, MI, procedural failure, or major bleeding was not significantly reduced by enoxaparin (17% relative risk reduction, P = 0.063), but there was a reduction in the composite main secondary endpoint of death, recurrent MI or ACS, or urgent revascularization. Importantly, there was no evidence of increased bleeding following the use of enoxaparin over UFH. ²⁰⁰ In the per-protocol analysis of the ATOLL trial (87% of the study population), i.v. enoxaparin was superior to UFH in reducing the primary endpoint, ischaemic endpoints, mortality, and major bleeding. ²⁰¹ In a meta-analysis of 23 PCI trials (30 966 patients, 33% primary PCI), enoxaparin was associated with a significant reduction in death compared to UHF. This effect was particularly significant in the primary PCI context and was associated with a reduction in major bleeding. ²⁰² Based on these considerations, enoxaparin should be considered in STEMI.

Five dedicated randomized controlled trials have compared bivalirudin with UFH with or without planned use of GP IIb/IIIa inhibitors in patients with STEMI. ^{197 , 203–207} A meta-analysis of these trials showed no mortality advantage with bivalirudin and a reduction in the risk of major bleeding, but at the cost of an increased risk of acute stent thrombosis. ²⁰⁸ In the recent MATRIX trial including 7213 ACS patients (56% with STEMI), bivalirudin did not reduce the incidence of the primary endpoint (composite of death, MI, or stroke) compared to UFH. Bivalirudin was associated with lower total and cardiovascular mortality, lower bleeding, and more definite stent thrombosis. ²⁰⁹ The recently published STEMI subanalysis confirmed a lack of statistical interaction between the type of ACS and outcomes within the study. ²¹⁰ The MATRIX trial showed that prolonging bivalirudin infusion after PCI did not improve the outcomes compared with bivalirudin infusion confined to the duration of PCI. ²⁰⁹ However, a post hoc analysis suggested that prolonging bivalirudin with a full-PCI dose after PCI was associated with the lowest risk of ischaemic and bleeding events, which is in accordance with the current label of the drug. ²⁰⁹ Based on these data, bivalirudin should be considered in STEMI, especially in patients at high bleeding risk. ^{197 , 211 , 212} Bivalirudin is recommended for patients with heparin-induced thrombocytopenia.

Routine post-procedural anticoagulant therapy is not indicated after primary PCI, except when there is a separate indication for either full-dose anticoagulation [due, for instance, to atrial fibrillation (AF), mechanical valves, or LV thrombus) ² or prophylactic doses for the prevention of venous thromboembolism in patients requiring prolonged bed rest.

Periprocedural and post-procedural antithrombotic therapy ^a in patients undergoing primary percutaneous coronary intervention

GP = glycoprotein; i.v. = intravenous; PCI = percutaneous coronary intervention; UFH = unfractionated heparin.

a

Dose regimens are specified in Table 6.

b

Class of recommendation.

c

Level of evidence.

Periprocedural and post-procedural antithrombotic therapy ^a in patients undergoing primary percutaneous coronary intervention

GP = glycoprotein; i.v. = intravenous; PCI = percutaneous coronary intervention; UFH = unfractionated heparin.

a

Dose regimens are specified in Table 6.

b

Class of recommendation.

c

Level of evidence.

Table 6

Doses of antiplatelet and anticoagulant cotherapies in patients undergoing primary percutaneous coronary intervention or not reperfused

b.i.d. = twice a day; GP = glycoprotein; i.v. = intravenous; IU = international units; PCI = percutaneous coronary intervention; UFH = unfractionated heparin.

Table 6

Doses of antiplatelet and anticoagulant cotherapies in patients undergoing primary percutaneous coronary intervention or not reperfused

b.i.d. = twice a day; GP = glycoprotein; i.v. = intravenous; IU = international units; PCI = percutaneous coronary intervention; UFH = unfractionated heparin.

5.2.2.3 Therapies to reduce infarct size and microvascular obstruction

Final infarct size and MVO are major independent predictors of long-term mortality and heart failure in survivors of STEMI. ^{216 , 217} MVO is defined as inadequate myocardial perfusion after successful mechanical opening of the IRA, and is caused by several factors. ²¹⁸ MVO is diagnosed immediately after PCI when post-procedural angiographic TIMI flow is < 3, or in the case of a TIMI flow of 3 when myocardial blush grade is 0 or 1, or when ST resolution within 60–90 min of the procedure is < 70%. Other non-invasive techniques to diagnose MVO are late gadolinium enhancement (LGE) CMR (the current state of the art for MVO identification and quantification), contrast echocardiography, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). ²¹⁸ Different strategies, such as coronary post-conditioning, remote ischaemic conditioning, early i.v. metoprolol, GP IIb/IIIa inhibitors, drugs targeting mitochondrial integrity or nitric oxide pathways, adenosine, glucose modulators, hypothermia, and others, have been shown to be beneficial in pre-clinical and small-scale clinical trials, ^{217 , 219} but still there is no therapy aimed at reducing ischaemia/reperfusion injury (MI size) that is clearly associated with improved clinical outcomes. The reduction of ischaemia/reperfusion injury in general, and MVO in particular, remains an unmet need to further improve long-term ventricular function in STEMI.

5.3 Fibrinolysis and pharmacoinvasive strategy

5.3.1 Benefit and indication of fibrinolysis

Fibrinolytic therapy is an important reperfusion strategy in settings where primary PCI cannot be offered in a timely manner, and prevents 30 early deaths per 1000 patients treated within 6 h after symptom onset. ²²⁰ The largest absolute benefit is seen among patients at highest risk, including the elderly, and when treatment is offered <2 h after symptom onset. ^{138 , 221} Fibrinolytic therapy is recommended within 12 h of symptom onset if primary PCI cannot be performed within 120 min from STEMI diagnosis (see Figure 3) and there are no contraindications. The later the patient presents (particularly after 3 h), ^{98 , 120 , 121} the more consideration should be given to transfer for primary PCI (as opposed to administering fibrinolytic therapy) because the efficacy and clinical benefit of fibrinolysis decrease as the time from symptom onset increases. ¹²⁰ In the presence of contraindications for fibrinolytic treatment, it is important to weigh the potentially life-saving effect of fibrinolysis against potentially life-threatening side effects, taking into account alternative treatment options such as delayed primary PCI.

DAPT = dual antiplatelet therapy; IRA = infarct-related artery; i.v. = intravenous; PCI = percutaneous coronary intervention; SBP = systolic blood pressure; s.c. = subcutaneous; STEMI = ST-segment elevation myocardial infarction; UFH = unfractionated heparin.

a

Class of recommendation.

b

Level of evidence.

c

Clopidogrel is the P2Y₁₂ inhibitor of choice as co-adjuvant and after fibrinolysis, but 48 h after fibrinolysis, switch to prasugrel/ticagrelor may be considered in patients who underwent PCI.

DAPT = dual antiplatelet therapy; IRA = infarct-related artery; i.v. = intravenous; PCI = percutaneous coronary intervention; SBP = systolic blood pressure; s.c. = subcutaneous; STEMI = ST-segment elevation myocardial infarction; UFH = unfractionated heparin.

a

Class of recommendation.

b

Level of evidence.

c

Clopidogrel is the P2Y₁₂ inhibitor of choice as co-adjuvant and after fibrinolysis, but 48 h after fibrinolysis, switch to prasugrel/ticagrelor may be considered in patients who underwent PCI.

Doses of fibrinolytic agents and antithrombotic co-therapies are listed in Table 7.

Table 7

Doses of fibrinolytic agents and antithrombotic co-therapies

^aPTT = activated partial thromboplastin time; eGFR = estimated glomerular filtration rate; i.v. = intravenous; IU = international units; rPA = recombinant plasminogen activator; s.c. = subcutaneous; tPA = tissue plasminogen activator; UFH = unfractionated heparin.

Table 7

Doses of fibrinolytic agents and antithrombotic co-therapies

^aPTT = activated partial thromboplastin time; eGFR = estimated glomerular filtration rate; i.v. = intravenous; IU = international units; rPA = recombinant plasminogen activator; s.c. = subcutaneous; tPA = tissue plasminogen activator; UFH = unfractionated heparin.

5.3.2 Pre-hospital fibrinolysis

In a meta-analysis of six randomized trials (n = 6434), pre-hospital fibrinolysis reduced early mortality by 17% compared with in-hospital fibrinolysis, ¹²³ particularly when administered in the first 2 h of symptom onset. ¹³⁸ These and more recent data support pre-hospital initiation of fibrinolytic treatment when a reperfusion strategy is indicated. ^{97 , 99 , 100 , 237} The STREAM trial showed that pre-hospital fibrinolysis followed by an early PCI strategy was associated with a similar outcome as transfer for primary PCI in STEMI patients presenting within 3 h after symptom onset who could not undergo primary PCI within 1 h after FMC. ^{121 , 238}

If trained medical or paramedical staff are able to analyse the ECG on-site or to transmit the ECG to the hospital for interpretation, it is recommended to initiate fibrinolytic therapy in the pre-hospital setting. The aim is to start fibrinolytic therapy within 10 min from STEMI diagnosis.

5.3.3 Angiography and percutaneous coronary intervention after fibrinolysis (pharmacoinvasive strategy)

Following initiation of lytic therapy, it is recommended to transfer the patients to a PCI centre (Figure 3). In cases of failed fibrinolysis, or if there is evidence of reocclusion or reinfarction with recurrence of ST-segment elevation, immediate angiography and rescue PCI is indicated. ¹²⁴ In this setting, re-administration of fibrinolysis has not been shown to be beneficial and should be discouraged. ¹²⁴ Even if it is likely that fibrinolysis will be successful (ST-segment resolution > 50% at 60–90 min; typical reperfusion arrhythmia; and disappearance of chest pain), a strategy of routine early angiography is recommended if there are no contraindications. Several randomized trials ^{126–128 , 234 , 239 , 240} and meta-analyses ^{129 , 130} have shown that early routine angiography with subsequent PCI (if needed) after fibrinolysis reduced the rates of reinfarction and recurrent ischaemia compared with a 'watchful waiting' strategy, in which angiography and revascularization were indicated only in patients with spontaneous or induced severe ischaemia or LV dysfunction, or in those with a positive outpatient ischaemia test. The benefits of early routine PCI after fibrinolysis were seen in the absence of an increased risk of adverse events (stroke or major bleeding), and across patient subgroups. ²⁴¹ Thus, early angiography with subsequent PCI if indicated is also the recommended standard of care after successful fibrinolysis (see Figure 3).

A crucial issue is the optimal time delay between successful lysis and PCI; there was a wide variation in delay in trials, from a median of 1.3 h in the Combined Angioplasty and Pharmacological Intervention versus Thrombolytics ALone in Acute Myocardial Infarction (CAPITAL AMI) trial ²⁴⁰ to 17 h in the Grupo de Análisis de la Cardiopatía Isquémica Aguda (GRACIA)-1 ²³⁴ and STREAM trials. ¹²¹ In a pooled patient-level analysis of six randomized trials, very early angiography (<2 h) after fibrinolysis was not associated with an increased risk of 30 day death/reinfarction or in-hospital major bleeding, and a shorter time from symptom onset to angiography (<4 h) was associated with reduced 30 day and 1 year death/reinfarction and 30 day recurrent ischaemia. ¹²⁵ Based on this analysis, as well as on trials having a median delay between start of lysis and angiography of 2–17 h, ^{121 , 126–128} a time-window of 2–24 h after successful lysis is recommended.

5.3.4 Comparison of fibrinolytic agents

A fibrin-specific agent should be preferred. ²²⁴ Single-bolus weight-adjusted tenecteplase tissue plasminogen activator (TNK-tPA) is equivalent to accelerated tPA in reducing 30 day mortality, but is safer in preventing non-cerebral bleeds and blood transfusion, and is easier to use in the pre-hospital setting. ²²³

5.3.5 Adjunctive antiplatelet and anticoagulant therapies

An early study showed that the benefits of aspirin and fibrinolytics (i.e. streptokinase) were additive. ²¹³ The first dose of aspirin should be chewed or given i.v. and a low dose (75–100 mg) given orally daily thereafter. Clopidogrel added to aspirin reduces the risk of cardiovascular events and overall mortality in patients treated with fibrinolysis ^{225 , 226} and should be added to aspirin as an adjunct to lytic therapy. Prasugrel and ticagrelor have not been studied as adjuncts to fibrinolysis. There is no evidence that administration of GP IIb/IIIa inhibitors improves myocardial perfusion or outcomes in patients treated with fibrinolysis, and bleeding may increase. ²⁴²

Parenteral anticoagulation should preferably be given until revascularization (if performed). Otherwise, it should be given for at least 48 h or for the duration of hospital stay, up to 8 days. In spite of an increased risk of major bleeding, the net clinical benefit favoured enoxaparin over UFH in the ASsessment of the Safety and Efficacy of a New Thrombolytic 3 (ASSENT 3) trial (n = 6095). ²²⁷ In the large Enoxaparin and Thrombolysis Reperfusion for Acute myocardial infarction Treatment–Thrombolysis In Myocardial Infarction 25 (ExTRACT–TIMI 25) trial (n = 20 506), a lower dose of enoxaparin was given to patients ≥75 years of age and to those with impaired renal function (estimated creatinine clearance <30 mL/min). Enoxaparin was associated with a reduction in the risk of death and reinfarction at 30 days when compared with a weight-adjusted UFH dose, but at the cost of a significant increase in non-cerebral bleeding complications. The net clinical benefit (i.e. absence of death, non-fatal infarction, and intracranial haemorrhage) favoured enoxaparin. ^{229 , 230} Finally, fondaparinux was shown in the large OASIS-6 trial to be superior in this setting to placebo or UFH in preventing death and reinfarction, ^{199 , 233} especially in patients who received streptokinase.

In a large trial with streptokinase, ²⁴³ significantly fewer reinfarctions were seen with bivalirudin given for 48 h compared with UFH, though at the cost of a modest and non-significant increase in non-cerebral bleeding complications. Bivalirudin has not been studied with fibrin-specific agents. Thus, there is no evidence in support of direct thrombin inhibitors as an adjunct to fibrinolysis.

Weight-adjusted i.v. tenecteplase, aspirin, and clopidogrel given orally, and enoxaparin i.v. followed by s.c. administration until the time of PCI (revascularisation), comprise the antithrombotic cocktail most extensively studied as part of a pharmacoinvasive strategy. ^{121 , 126 , 128 , 242 , 244}

5.3.6 Hazards of fibrinolysis

Fibrinolytic therapy is associated with a small but significant excess of strokes, largely attributable to cerebral haemorrhage, with the excess hazard appearing on the first day after treatment. ²²⁰ Advanced age, lower weight, female sex, previous cerebrovascular disease, and systolic and diastolic hypertension on admission are significant predictors of intracranial haemorrhage. ²⁴⁵ In the latest trials, intracranial bleeding occurred in 0.9–1.0% of the total population studied. ^{121 , 223 , 246} In the STREAM trial, the initial excess in intracranial haemorrhage in patients ≥75 years was reduced after the protocol amendment to reduce the dose of tenecteplase by 50%. Data from a number of studies suggest that major non-cerebral bleeds occurred in 4–13% of the patients treated. ^{121 , 223 , 224 , 246} Administration of streptokinase may be associated with hypotension, but severe allergic reactions are rare. Re-administration of streptokinase should be avoided because of antibodies that can impair its activity, and because of the risk of allergic reactions.

5.3.7 Contraindications to fibrinolytic therapy

Short successful resuscitation does not contraindicate fibrinolytic therapy. In patients in refractory cardiac arrest, lytic therapy is not effective, increases the risk of bleeding, and is therefore not recommended. Prolonged, or traumatic but successful, resuscitation increases bleeding risk and is a relative contraindication to fibrinolysis. ²⁴⁷ Table 8 lists the absolute and relative contraindications to fibrinolytic therapy.

Table 8

Contra-indications to fibrinolytic therapy

DBP = diastolic blood pressure; SBP = systolic blood pressure.

Table 8

Contra-indications to fibrinolytic therapy

DBP = diastolic blood pressure; SBP = systolic blood pressure.

5.4 Coronary artery bypass graft surgery

Emergent coronary artery bypass graft surgery (CABG) should be considered for patients with a patent IRA but with unsuitable anatomy for PCI, and either a large myocardial area at jeopardy or with cardiogenic shock. ²⁴⁸ In patients with MI-related mechanical complications who require coronary revascularization, CABG is recommended at the time of repair. In STEMI patients with failed PCI or coronary occlusion not amenable to PCI, emergent CABG is infrequently performed because the benefits of surgical revascularization in this setting are uncertain. As the delay to reperfusion is long, the probabilities of myocardial salvage affecting prognosis are low and the surgical risks are elevated.

In the absence of randomized data, optimal timing for non-emergent CABG in stabilized post-MI patients should be determined individually. A review of California discharge data compared patients who underwent early (<3 days, n = 4676) versus delayed (≥3 days, n = 4800) post-MI CABG. ²⁴⁹ Patients who underwent early CABG had a higher mortality rate (unadjusted mortality 5.6% vs. 3.8%; propensity-adjusted odds ratio 1.40, 95% CI 1.12–1.74; P < 0.001), with the highest mortality observed in patients on whom surgery was performed on the day of the MI (8.2%). However, no differentiation was made between NSTEMI and STEMI, and higher-risk patients were more likely to be treated rapidly. Patients with haemodynamic deterioration or who are at high risk of recurrent ischaemic events (i.e. patients with a large area of myocardium at jeopardy due to critical coronary stenoses or recurrent ischaemia) should be operated on as soon as possible without waiting for the full recovery of platelet function following discontinuation of DAPT. For all other patients, a waiting period of 3–7 days may be the best compromise (at least 3 days following interruption of ticagrelor, ^{187 , 250} 5 days for clopidogrel, and 7 days for prasugrel), ⁷ while it is recommended that aspirin is continued. ²⁵¹ The first aspirin administration post-CABG is recommended 6–24 h after surgery in the absence of ongoing bleeding events. ^{252 , 253}

6. Management during hospitalization and at discharge

6.1 Coronary care unit/intensive cardiac care unit

Following reperfusion, it is recommended to admit STEMI patients to a CCU/ICCU or equivalent unit where continuous monitoring and specialized care can be provided. The staff should be thoroughly familiar with the management of ACS, arrhythmias, heart failure, mechanical circulatory support, invasive and non-invasive haemodynamic monitoring (arterial and pulmonary artery pressures), respiratory monitoring, mechanical ventilation, and targeted temperature management. The unit should also be able to manage patients with serious renal and pulmonary disease. The desirable organization, structure, and criteria of the CCU/ICCU have been described in an ESC-Acute Cardiovascular Care Association (ACCA) position paper. ²⁵⁴

6.2 Monitoring

ECG monitoring for arrhythmias and ST-segment deviations is recommended for at least 24 h after symptom onset in all STEMI patients. Longer monitoring should be considered in patients at intermediate- to high-risk for cardiac arrhythmias (those with more than one of the following criteria: haemodynamically unstable, presenting major arrhythmias, LVEF <40%, failed reperfusion, additional critical coronary stenoses of major vessels, or complications related to PCI). Further monitoring for arrhythmias depends on estimated risk. When a patient leaves the CCU/ICCU or equivalent, monitoring may be continued by telemetry. It is recommended that personnel adequately equipped and trained to manage life-threatening arrhythmias and cardiac arrest accompany patients who are transferred between facilities during the time-window in which they require continuous rhythm monitoring.

6.3 Ambulation

Early ambulation (day 1) is recommended in the majority of patients and is facilitated by using the radial access for PCI. Patients with extensive myocardial damage, heart failure, hypotension, or arrhythmias may initially rest in bed before assessment of myocardial function and achievement of clinical stabilization. Prolongation of bed rest and limitation of physical activity may occasionally be needed for patients with large infarcts or with severe complications depending on symptoms and ability.

6.4 Length of stay

The optimal length of stay in the CCU/ICCU and hospital should be determined on an individual basis, according to the patient's cardiac risk, comorbidities, functional status, and social support. Generalization of successful reperfusion and knowledge of coronary anatomy has led to progressive reductions in length of stay after STEMI, with significant reductions in 30 day mortality, suggesting that earlier discharge is not associated with late mortality. ^{255 , 256} Several studies have shown that low-risk patients with successful primary PCI and complete revascularization can safely be discharged from hospital on day 2 or day 3 after PCI. ^256–262 Candidates for early discharge after STEMI can be identified using simple criteria [e.g. the Second Primary Angioplasty in Myocardial Infarction (PAMI-II) criteria, the Zwolle primary PCI Index, or other criteria]. ^{257 , 258} The PAMI-II criteria designate as low risk patients aged <70 years, with an LVEF >45%, one- or two-vessel disease, successful PCI, and no persistent arrhythmias. A short hospital stay implies limited time for proper patient education and up-titration of secondary prevention treatments. Consequently, these patients should have early post-discharge consultations with a cardiologist, primary care physician, or specialized nurse scheduled and be rapidly enrolled in a formal rehabilitation programme, either in-hospital or on an outpatient basis.

Early (i.e. same day) transfer to a local hospital following successful primary PCI is routine practice. This can be done safely under adequate monitoring and supervision in selected patients, i.e. those without signs or symptoms consistent with ongoing myocardial ischaemia, without arrhythmia, who are haemodynamically stable, not requiring vasoactive or mechanical support, and are not scheduled for further revascularization. ²⁶³

Logistical issues for hospital stay

CCU = coronary care unit; ICCU = intensive cardiac care unit; LVEF = left ventricular ejection fraction; PAMI-II, Second Primary Angioplasty in Myocardial Infarction; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

c

For example, PAMI-II criteria: age <70 years, LVEF >45%, one- or two-vessel disease, successful PCI and no persistent arrhythmias.

Logistical issues for hospital stay

CCU = coronary care unit; ICCU = intensive cardiac care unit; LVEF = left ventricular ejection fraction; PAMI-II, Second Primary Angioplasty in Myocardial Infarction; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

c

For example, PAMI-II criteria: age <70 years, LVEF >45%, one- or two-vessel disease, successful PCI and no persistent arrhythmias.

6.5 Special patient subsets

Several specific patient subsets deserve particular consideration.

6.5.1 Patients taking oral anticoagulation

Many patients presenting with STEMI are previously on oral anticoagulation or require long-term anticoagulation afterwards. The addition of DAPT to oral anticoagulation increases the risk of bleeding complications two- to three-fold compared to anticoagulation alone. ^266–269

Management during STEMI: Given that oral anticoagulation is a relative contraindication for fibrinolysis, when these patients present with a STEMI, they should be triaged for primary PCI strategy regardless of the anticipated time to PCI-mediated reperfusion. Patients should receive additional parenteral anticoagulation, regardless of the timing of the last dose of oral anticoagulant. GP IIb/IIIa inhibitors should be avoided. Loading of aspirin should be done as in all STEMI patients, and clopidogrel is the P2Y₁₂ inhibitor of choice (600 mg loading dose) before or at the latest at the time of PCI. Prasugrel and ticagrelor are not recommended. Ideally, a chronic anticoagulation regimen should not be stopped during admission. Gastric protection with a proton pump inhibitor (PPI) is recommended.

Maintenance after STEMI: In general, continuation of oral anticoagulation in patients with an indication for DAPT (e.g. after STEMI) should be evaluated carefully and continued only if compelling evidence exists. Ischaemic and bleeding risks should be taken into consideration. While there is a considerable overlap of risk factors associated with ischaemic with bleeding outcomes, multiple bleeding risk scores outperform CHA₂DS₂-VASc [Cardiac failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled) – VAScular disease, Age 65–74 and Sex category (Female)] in predicting bleeding risk. ^{270 , 271}

For most patients, triple therapy (in the form of oral anticoagulation, aspirin, and clopidogrel) should be considered for 6 months. Then, oral anticoagulation plus aspirin or clopidogrel should be considered for an additional 6 months. After 1 year, it is indicated to maintain only oral anticoagulation. In cases of very high bleeding risk, triple therapy can be reduced to 1 month after STEMI, continuing on dual therapy (oral anticoagulation plus aspirin or clopidogrel) up to 1 year, and thereafter only anticoagulation. ^{5 , 7}

The dose intensity of oral anticoagulation should be carefully monitored with a target international normalized ratio in the lower part of the recommended target range. When non-vitamin K antagonist oral anticoagulants are used, the lowest effective tested dose for stroke prevention should be applied. In general, dose reduction below the approved dose is not recommended. Recently, the Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects with Atrial Fibrillation who Undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) study randomized 2124 patients with non-valvular AF, who had undergone PCI with stenting (∼12% STEMI patients), to receive low-dose rivaroxaban [15 mg o.d. (once a day)] plus a P2Y₁₂ inhibitor (93% clopidogrel) and no aspirin for 12 months, very-low-dose rivaroxaban (2.5 mg b.i.d.) plus DAPT (95% clopidogrel) for 1, 6, or 12 months, or standard therapy with a dose-adjusted vitamin K antagonist plus DAPT (96% clopidogrel) for 1, 6, or 12 months. ²⁷² The primary safety endpoint (TIMI clinically significant bleeding) was lower in the two groups receiving rivaroxaban. No difference in major bleeding or transfusion was observed across groups. However, this study was underpowered for assessing differences in ischaemic events such as stent thrombosis or stroke rates. Therefore, uncertainty remains regarding the comparative performance of three tested antithrombotic regimens in patients at high stroke and/or stent thrombosis risk.

6.5.2 Elderly patients

Owing to the ageing of the population, a higher proportion of elderly patients is expected to present with STEMI. As these patients may present with atypical symptoms, the diagnosis of MI may be delayed or missed. ²⁷ In addition, the elderly have more comorbidities and are less likely to receive reperfusion therapy compared with younger patients. ^{273 , 274} Elderly patients are also at particular risk of bleeding and other complications from acute therapies because bleeding risk increases with age, renal function tends to decrease, and the prevalence of comorbidities is high. Observational studies have shown frequent excess dosing of antithrombotic therapies in elderly patients. ²⁷⁵ Furthermore, they have a higher risk of mechanical complications.

It is key to maintain a high index of suspicion for MI in elderly patients who present with atypical complaints, treating them as recommended, and using specific strategies to reduce bleeding risk; these include paying attention to proper dosing of antithrombotic therapies, particularly in relation to renal function, frailty, or comorbidities, and using radial access whenever possible. There is no upper age limit with respect to reperfusion, especially with primary PCI. ²⁷⁶

6.5.3 Renal dysfunction

Renal dysfunction [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m²] is present in approximately 30–40% of patients with ACS and is associated with a worse prognosis and increased risk of in-hospital complications. ²⁷⁷ Owing to differences in presentation (less frequent presentation with chest pain and fewer typical ECG signs) diagnosis may be delayed.

Although decisions on reperfusion in patients with STEMI have to be made before any assessment of renal function is available, it is important to estimate the GFR as soon as possible. The type and dose of antithrombotic agent (see Table 9) and the amount of contrast agent should be considered based on renal function. ²⁷⁷ ACS patients with chronic kidney disease (CKD) receive frequently excess dosing with antithrombotics, contributing to the increased bleeding risk. ²⁷⁵ Consequently, in patients with known or anticipated reduction of renal function, several antithrombotic agents should either be withheld or their doses reduced appropriately. Ensuring proper hydration during and after primary PCI and limiting the dose of contrast agents, preferentially low-osmolality contrast agents, are important steps in minimizing the risk of contrast-induced nephropathy. ¹

Table 9

Recommended doses of antithrombotic agents in the acute care of patients with chronic kidney disease

aPTT = activated partial thromboplastin time; CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; GP = glycoprotein; IU = international units; i.v. = intravenous; PCI = percutaneous coronary intervention; s.c. = subcutaneous; UFH = unfractionated heparin.

a

Double bolus if administered during primary PCI.

Table 9

Recommended doses of antithrombotic agents in the acute care of patients with chronic kidney disease

aPTT = activated partial thromboplastin time; CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; GP = glycoprotein; IU = international units; i.v. = intravenous; PCI = percutaneous coronary intervention; s.c. = subcutaneous; UFH = unfractionated heparin.

a

Double bolus if administered during primary PCI.

6.5.4 Non-reperfused patients

Patients who, for specific reasons (e.g. long delay), fail to receive reperfusion therapy within the recommended time (first 12 h) should immediately be evaluated clinically to rule out the presence of clinical, haemodynamic, or electrical instability. A primary PCI strategy is indicated in the presence of signs or symptoms suggestive of ongoing myocardial ischaemia, heart failure, haemodynamic instability, or life-threatening arrhythmias, ¹⁴¹ and should be considered in stable asymptomatic patients between 12–48 h after symptom onset. ^{133 , 142} After that time, either a non-invasive test for the presence of residual myocardial ischaemia/viability to decide a late invasive strategy or elective coronary angiography should be considered. However, routine PCI is not indicated in totally occluded IRA beyond the first 48 h from symptom onset due to the increased risk of late complications (see Figure 4). ^{135 , 137}

Figure 4

Reperfusion strategies in the infarct-related artery according to time from symptoms onset. PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

In early presenters (i.e. those with STEMI diagnosis within 3 hours from symptoms onset), a primary PCI strategy is the reperfusion strategy of choice. If the anticipated time from STEMI diagnosis to PCI-mediated reperfusion is > 120 min, then immediate fibrinolysis is indicated. After 3 hours (and up to 12 hours) of symptoms onset, the later the patient presents, the more consideration should be given to a primary PCI strategy as opposed to administering fibrinolytic therapy. In evolved STEMI (12–48 hours after symptoms onset), a routine primary PCI strategy (urgent angiography and subsequent PCI if indicated) should be considered in all patients. After 48 hours (recent STEMI) angiography should be performed but routine PCI of a total occluded IRA is not recommended. Regardless of the time from symptoms onset, the presence of ongoing symptoms suggestive of ischaemia, haemodynamic instability, or lifethreatening arrhythmias is an indication for a primary PCI strategy.

Figure 4

Reperfusion strategies in the infarct-related artery according to time from symptoms onset. PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

In early presenters (i.e. those with STEMI diagnosis within 3 hours from symptoms onset), a primary PCI strategy is the reperfusion strategy of choice. If the anticipated time from STEMI diagnosis to PCI-mediated reperfusion is > 120 min, then immediate fibrinolysis is indicated. After 3 hours (and up to 12 hours) of symptoms onset, the later the patient presents, the more consideration should be given to a primary PCI strategy as opposed to administering fibrinolytic therapy. In evolved STEMI (12–48 hours after symptoms onset), a routine primary PCI strategy (urgent angiography and subsequent PCI if indicated) should be considered in all patients. After 48 hours (recent STEMI) angiography should be performed but routine PCI of a total occluded IRA is not recommended. Regardless of the time from symptoms onset, the presence of ongoing symptoms suggestive of ischaemia, haemodynamic instability, or lifethreatening arrhythmias is an indication for a primary PCI strategy.

Early echocardiography with LVEF assessment is indicated in all patients. Medical therapy should include DAPT, anticoagulation, and secondary prevention therapies. In patients in whom PCI is finally performed, ticagrelor or prasugrel are preferred, ^{186 , 187} while in patients who do not undergo PCI, clopidogrel is indicated. ²²⁵ Anticoagulation, preferably with fondaparinux, is indicated until coronary revascularisation is done or hospital discharge. ¹⁹⁹ These patients are often undertreated. Therefore, it is important to emphasize that they should receive all the same secondary prevention medical therapies as those who receive timely reperfusion.

6.5.5 Patients with diabetes

Patients with diabetes are known to present with atypical chest pain more frequently than patients without diabetes and consequently may receive delayed initiation of treatment. ²⁷⁸ In addition, diabetic patients are characterized by a more diffuse atherosclerotic disease. ²⁷⁹ Although patients with diabetes are at higher risk of death and complications (including repeat revascularization after PCI), selection of antithrombotic therapies and reperfusion therapy is the same as in patients without diabetes. Regarding the use of antiplatelet drugs, the more potent oral P2Y₁₂ receptor inhibitors (prasugrel or ticagrelor) have consistently shown increased relative benefits with higher absolute risk reductions in patients with diabetes compared with clopidogrel. ²⁸⁰ On admission, it is recommended to evaluate glycaemic status in all STEMI patients with and without a known history of diabetes or hyperglycaemia, and to monitor it frequently in diabetic patients and patients with hyperglycaemia. In critically ill patients, there is a high risk of hypoglycaemia-related events when using intensive insulin therapy. ²⁸¹ In the absence of robust data to guide the optimal glucose management (e.g. treatment thresholds and glucose targets) in STEMI patients, a close but not too strict glucose control seems the best approach. In the acute phase, it is reasonable to manage hyperglycaemia (i.e. maintain a blood glucose concentration ≤11.0 mmol/L or 200 mg/dL) but absolutely avoid hypoglycaemia. ²⁸² To assess the risk of renal insufficiency, it is recommended to measure eGFR in patients on metformin and/or sodium-glucose co-transporter-2 (SGLT2) inhibitors.

Management of hyperglycaemia

ACS = acute coronary syndrome; PCI = percutaneous coronary intervention; SGLT2 = sodium-glucose co-transporter-2.

a

Class of recommendation.

b

Level of evidence.

c

A short withdrawal of metformin may be considered after an invasive coronary procedure.

Management of hyperglycaemia

ACS = acute coronary syndrome; PCI = percutaneous coronary intervention; SGLT2 = sodium-glucose co-transporter-2.

a

Class of recommendation.

b

Level of evidence.

c

A short withdrawal of metformin may be considered after an invasive coronary procedure.

6.6. Risk assessment

6.6.1 Clinical risk assessment

All patients with STEMI should have an early assessment of short-term risk, including an evaluation of the extent of myocardial damage, the occurrence of successful reperfusion, and the presence of clinical markers of high risk of further events including older age, fast heart rate, hypotension, Killip class >I, anterior MI, previous MI, elevated initial serum creatinine, history of heart failure, or peripheral arterial disease. Several risk scores have been developed, based on readily identifiable parameters in the acute phase before reperfusion. ^{264 , 283} The Global Registry of Acute Coronary Events (GRACE) risk score is recommended for risk assessment and adjustment. ^{283 , 284} All patients should also have an evaluation of long-term risk before discharge, including LVEF, severity of CAD and completeness of coronary revascularization, residual ischaemia, occurrence of complications during hospitalization, and levels of metabolic risk markers, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting triglycerides, and plasma glucose, as well as renal function. As LDL-C levels tend to decrease during the first days after MI, they should be measured as soon as possible after admission.

Patients who do not get successful reperfusion are at higher risk of early complications and death. These patients should have an assessment of the presence of residual ischaemia and, if appropriate, myocardial viability. Because the risk of events decreases with time, early risk assessment is indicated.

6.6.2 Non-invasive imaging in management and risk stratification

LV dysfunction is a key prognostic factor. Therefore, it is recommended that the LVEF is determined before hospital discharge in all STEMI patients. Emergency echocardiography at presentation is indicated in patients with cardiac arrest, cardiogenic shock, haemodynamic instability or suspected mechanical complications, and if the diagnosis of STEMI is uncertain. Routine echocardiography after primary PCI is recommended to assess resting LV function, as well as RV and valve function, to exclude early post-infarction mechanical complications and LV thrombus. This assessment is usually performed with echocardiography, but in the limited cases in which echocardiography may be suboptimal or inconclusive, CMR may be a good alternative. Patients with multivessel disease in which only the IRA lesion has been treated, or patients with late-presenting STEMI, may benefit from additional assessment for residual ischaemia or viability. Treatment of non-IRA lesions in patients with multivessel disease is discussed in section 5.2.1.4. In patients presenting days after the acute event with a completed MI, the presence of recurrent angina or documented ischaemia and proven viability in a large myocardial territory may help define a strategy of planned revascularization of an occluded IRA, ^{135 , 285 , 286} although the evidence is controversial.

The timing of and best imaging technique (echocardiography, SPECT, CMR, or PET) to detect residual ischaemia and myocardial viability remains to be determined, but will also depend on local availability and expertise. The best validated and widely available tests are stress echocardiography and SPECT (both used in combination with exercise or pharmacological stress), but PET and CMR are equally indicated. However, in post-MI patients, the detection of residual ischaemia by echocardiography is challenging due to existing wall motion abnormalities. ²⁸⁷ LGE-CMR imaging has a high diagnostic accuracy for assessing the transmural extent of myocardial scar tissue. ²⁸⁸ However, the ability to detect viability and predict recovery of wall motion is not significantly superior to other imaging techniques. ²⁸⁹ The presence of dysfunctional viable myocardium by LGE-CMR is an independent predictor of mortality in patients with ischaemic LV dysfunction. ²⁹⁰

More recently, the presence of wall thinning with limited scar burden was shown to be associated with improved contractility and resolution of wall thinning after revascularization, emphasizing the importance of viability beyond wall thickness and myocardial revascularization to improve prognosis. ²⁹¹ PET is also a high-resolution technique but its use is limited by cost and availability. A randomized clinical trial with PET imaging demonstrated that patients with a substantial amount of dysfunctional but viable myocardium are likely to benefit from myocardial revascularization and may show improvements in regional and global contractile function, symptoms, exercise capacity, and long-term prognosis. ²⁹² The association between viability and improved survival after revascularisation was also demonstrated by a meta-analysis. ²⁹³

In patients with a pre-discharge LVEF ≤40%, re-evaluation of LVEF 6–12 weeks after complete revascularization and optimal medical therapy is recommended to assess the potential need for primary prevention implantable cardioverter defibrillator (ICD) implantation. ³ Additional parameters that are measured by imaging in these patients and that could be used as endpoints in clinical trials are: (1) infarct size (CMR, SPECT, and PET); (2) myocardium at risk (SPECT, CMR); (3) MVO (CMR); and (4) intra-myocardial haemorrhage (CMR). Infarct size and MVO are predictors of long-term mortality and heart failure in STEMI survivors. ^{216 , 217 , 294}

Summary of indications for imaging and stress testing in ST-elevation myocardial infarction patients

CAD = coronary artery disease; CMR = cardiac magnetic resonance; CT = computed tomography; ICD = implantable cardioverter defibrillator; LV = left ventricular; LVEF = left ventricular ejection fraction; MI = myocardial infarction; PCI = percutaneous coronary intervention; PET = positron emission tomography; RV = right ventricular; SPECT = single-photon emission computed tomography.

a

Class of recommendation.

b

Level of evidence.

Summary of indications for imaging and stress testing in ST-elevation myocardial infarction patients

CAD = coronary artery disease; CMR = cardiac magnetic resonance; CT = computed tomography; ICD = implantable cardioverter defibrillator; LV = left ventricular; LVEF = left ventricular ejection fraction; MI = myocardial infarction; PCI = percutaneous coronary intervention; PET = positron emission tomography; RV = right ventricular; SPECT = single-photon emission computed tomography.

a

Class of recommendation.

b

Level of evidence.

7. Long-term therapies for ST-segment elevation myocardial infarction

7.1 Lifestyle interventions and risk factor control

Key lifestyle interventions include cessation of smoking, optimal blood pressure control, diet advice and weight control, and encouraging physical activity. Detailed recommendations are available from the ESC Guidelines on prevention. ⁴ During hospitalization, the time for implementing secondary prevention is limited and a close collaboration between the cardiologist and the general practitioner, specialist rehabilitation nurses, pharmacists, dieticians, and physiotherapists is critically important. Habits of a lifetime are not easily changed, and the implementation and follow-up of these changes are a long-term undertaking.

7.1.1 Smoking cessation

Smoking has a strong pro-thrombotic effect, and smoking cessation is potentially the most (cost) effective of all secondary prevention measures. ³⁰¹ Smoking cessation interventions should start during hospitalization, when smoking is not allowed, and continue during the post-discharge follow-up period. ^{302 , 303} The beneficial effect of smoking cessation in patients with CAD, including a majority suffering an MI, has been shown in a meta-analysis (20 observational studies, including 12 603 patients) reporting a 36% reduction of mortality in quitters. ³⁰⁴

A significant number of CAD patients continue or restart smoking, illustrating the addictive nature of the smoking habit. ³⁰⁵ There is a strong evidence base for brief interventions, with a combination of behavioural support and pharmacotherapies including nicotine replacement therapy, bupropion, and varenicline. ^{305 , 306} Electronic cigarettes may also be helpful in achieving smoking cessation, as there is some evidence from two pooled randomized clinical trials (662 patients) showing that electronic cigarettes with nicotine had higher quit or reduced smoking rates when compared with placebo. ³⁰⁷

7.1.2 Diet, alcohol, and weight control

Current guidelines on prevention recommend: (i) a diet similar to the Mediterranean diet, which includes a maximum of 10% of total energy intake from saturated fat, by replacing it with polyunsaturated fatty acids and as little as possible of trans fatty acids; (ii) salt intake of < 5 g per day; (iii) 30–45 g fibre per day; (iv) ≥200 g fruits and 200 g vegetables per day; (v) fish 1–2 times per week (especially oily varieties); (vi) 30 g unsalted nuts daily; (vii) limited alcohol intake [maximum of 2 glasses (20 g of alcohol) daily for men and 1 for women]; and (viii) discouraging sugar-sweetened drinks. ⁴ Moderate alcohol consumption in abstainers is not recommended.

Overweight and obesity [body mass index (BMI) ≥25 kg/m²] is associated with higher all-cause mortality compared with a healthy weight (BMI between 20 kg/m² and <25 kg/m²). Abdominal fat is particularly harmful and weight loss has beneficial effects on cardiovascular disease risk factors. Consequently, maintaining a healthy weight or losing weight is recommended for all subjects, ³⁰⁸ including patients with STEMI. However, it has not been established that weight reduction per se reduces mortality.

7.1.3 Exercise-based cardiac rehabilitation

All AMI patients should participate in an exercise-based cardiac rehabilitation programme, ³⁰⁹ taking into account their age, pre-infarction level of activity, and physical limitations. A cardiac rehabilitation programme preferably includes exercise training, risk factor modification, education, stress management, and psychological support. ³⁰⁹ In a large meta-analysis, exercise training as part of a cardiac rehabilitation programme was associated with a 22% reduction in cardiac mortality rate in patients with CAD. ³⁰⁹ The benefit of cardiac rehabilitation appears to be through direct physiological effects of exercise training and through cardiac rehabilitation effects on risk factor control, lifestyle behaviours, and mood. ³¹⁰ An additional benefit in the context of a short hospital stay is to ensure proper titration and monitoring of key, evidence-based therapies after STEMI. Nowadays, most rehabilitation is offered as an outpatient programme of 8–24 weeks' duration. ^{311 , 312}

7.1.4 Resumption of activities

Return to work after AMI represents an important indicator of recovery. Younger women in particular are at greater risk of not returning to work, given evidence of their worse recovery after MI than similarly aged men. ³¹³ Decisions should be individualized, based on LV function, completeness of revascularization and rhythm control, and the job characteristics. Extended sick leave is usually not beneficial and light-to-moderate physical activity after discharge should be encouraged. Sexual activity can be resumed early if adjusted to physical ability.

Guidance on air travel including repatriation for patients suffering an MI abroad is constrained by limited data. Factors related to the clinical circumstances as well as length of travel, whether accompanied, and the degree of anxiety also play a role. For uncomplicated completely revascularized MI with LVEF >40% the risk is low and travelling is regarded as safe after hospital discharge (from day 3 onwards). In complicated STEMI, including patients with heart failure, LVEF <40%, residual ischaemia, and arrhythmia, travelling should be deferred until the condition is stable. ³¹⁴

7.1.5 Blood pressure control

Hypertension is a prevalent risk factor in patients admitted with STEMI and, consequently, blood pressure should be well controlled. In addition to lifestyle changes, including reduced salt intake, increased physical activity, and weight loss, pharmacotherapy with a systolic blood pressure (SBP) target of < 140 mmHg should be initiated. In elderly, frail patients, the target can be more lenient, whereas in patients at very high risk who tolerate multiple blood pressure-lowering drugs, a target of < 120 mmHg may be considered. ^{4 , 315 , 316} Despite the proven efficacy of this treatment, non-adherence to lifestyle interventions and medications may affect treatment effect.

7.1.6 Adherence to treatment

Low treatment adherence is an important barrier to achieving optimal treatment targets and is associated with worse outcomes. ³¹⁷ Delayed outpatient follow-up after AMI results in worse short- and long-term medication adherence. ³¹⁸ In a meta-analysis of 376 162 patients, adherence to cardiovascular medications was estimated to be about 57% after a median of 2 years. ³¹⁹

It is generally recognized that adherence is determined by the interplay of socioeconomic, medication-related, condition-related, health system-related, and patient-related factors. ³²⁰ A strategy to reduce poor adherence is the use of a fixed-dose combination or polypill, including key medications to reduce cardiovascular risk, as a once-daily dose pill. ^{321 , 322} The only study dedicated to post-MI patients is the recent phase 2 Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention (FOCUS) trial, ³²³ in which 695 patients post-MI were randomized to usual care or to a polypill-based strategy [polypill containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin]. In this trial, after 9 months of follow-up, the polypill group showed improved adherence compared with the group receiving separate medications. Larger trials are needed to confirm a clinical benefit in secondary prevention.

Although low adherence has been qualified as an ubiquitous problem, ³²⁴ healthcare professionals and patients should be aware of this challenge and optimize communication by providing clear information, simplify treatment regimens, aim at shared decision-making, and implement repetitive monitoring and feedback.

Behavioural aspects after ST-elevation myocardial infarction

STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

Behavioural aspects after ST-elevation myocardial infarction

STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

7.2 Antithrombotic therapy

Full text about long-term antithrombotic therapy can be found in the online Web Addenda. In addition, this topic is covered in great detail in the ESC Focused Update on DAPT in CAD published simultaneously with these guidelines. ⁷

7.2.1 Aspirin

Aspirin is recommended indefinitely in all patients with STEMI. ^{329 , 330} For long-term prevention, low aspirin doses (75–100 mg) are indicated due to similar anti-ischaemic and less adverse events than higher doses, as demonstrated in the CURRENT-OASIS 7 trial. ³³⁰

7.2.2 Duration of dual antiplatelet therapy and antithrombotic combination therapies

DAPT, combining aspirin and a P2Y₁₂ inhibitor (i.e. prasugrel, ticagrelor, or clopidogrel), is recommended in patients with STEMI who are undergoing primary PCI (for up to 12 months). ^{186 , 187} Clopidogrel is recommended for 1 month in patients treated with fibrinolysis without subsequent PCI. ^{225 , 226} Expanding the duration of DAPT up to 12 months should be considered in these patients.

For patients undergoing fibrinolysis and subsequent PCI, DAPT is recommended for 12 months. Clopidogrel is the P2Y₁₂ inhibitor of choice as co-adjuvant and after fibrinolysis. Potent P2Y₁₂ inhibitors have not been properly tested in patients undergoing fibrinolysis, and safety (i.e. bleeding complications) is not well established. However, in patients who underwent PCI after fibrinolysis, after a safety period (arbitrarily considered 48 h), there are no biological grounds to consider that potent P2Y₁₂ inhibitors will add risk and not exert a benefit over clopidogrel as in the primary PCI setting.

Whereas no dedicated study exists on optimal DAPT duration in patients at high bleeding risk, multiple studies have shown that shortening DAPT to 6 months, compared with 12 months or longer, reduces the risk of major bleeding complications, with no apparent trade-off in ischaemic events. ^{331 , 332}

Two major studies have shown the benefit towards reduction of non-fatal ischaemic events in patients receiving longer than 12 months of DAPT. ^{333 , 334} The DAPT Study included only roughly 10% of STEMI patients and no information has so far been provided with respect to the benefit of prolonging clopidogrel or prasugrel from 12 to 30 months in this patient subset. Hence, no formal recommendations are possible for the use of clopidogrel or prasugrel beyond 1 year. ³³⁴

More recently, the Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial examined two doses of ticagrelor (60 mg and 90 mg b.i.d.) vs. placebo in patients with a history of MI 1–3 years previously and with high-risk features; the study showed a reduction in MACE with 90 mg ticagrelor. ³³³ There was no reduction in total mortality, but there was a borderline signal towards reduced cardiovascular mortality (when both doses were pooled) consistent with the reduction in non-fatal outcomes. ³³³ The 60 mg (but not the 90 mg) ticagrelor (plus aspirin) regimen also significantly reduced the stroke risk compared with aspirin monotherapy. The ticagrelor regimen was associated with a significantly increased bleeding risk. Patients with previous STEMI comprised more than 50% of the overall PEGASUS-TIMI 54 population, and subgroup analysis has shown consistent results in patients with previous STEMI vs. NSTEMI. ³³³ According to the available data, extension of DAPT beyond 1 year (up to 3 years) in the form of aspirin plus ticagrelor 60 mg b.i.d. may be considered in patients who have tolerated DAPT without a bleeding complication and having one additional risk factor for ischaemic events.

Gastric protection with a PPI is recommended for patients with a history of gastrointestinal bleeding and is appropriate for patients with multiple risk factors for bleeding, such as advanced age, concurrent use of anticoagulants, steroids or non-steroidal anti-inflammatory drugs including high-dose aspirin, and Helicobacter pylori infection. ^335–337

In the Acute Coronary Syndrome–Thrombolysis In Myocardial Infarction 51 (ATLAS ACS 2–TIMI 51) trial (n = 15 526, 50% STEMI), a low dose of rivaroxaban (2.5 mg twice daily), on top of aspirin plus clopidogrel, reduced the composite primary endpoint of cardiovascular death, MI, or stroke, but also all-cause mortality, over a mean follow-up of 13 months. ³³⁸ Stent thrombosis was reduced by one-third. However, this was associated with a three-fold increase in non-CABG-related major bleeding and intracranial haemorrhage. ³³⁸ Based on the ATLAS ACS 2–TIMI 51 trial, in selected patients at low bleeding risk, the 2.5 mg dose of rivaroxaban may be considered in patients who receive aspirin and clopidogrel after STEMI.

Maintenance antithrombotic strategy after ST-elevation myocardial infarction

AMI = acute myocardial infarction; CAD = coronary artery disease; DAPT = dual antiplatelet therapy; eGFR = estimated glomerular filtration rate; LV = left ventricular; PCI = percutaneous coronary intervention; PPI = proton pump inhibitor; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

c

History of gastrointestinal bleeding, anticoagulant therapy, chronic non-steroidal anti-inflammatory drug/corticosteroid user, and ≥2 or more of the following: age ≥65 years, dyspepsia, gastro-oesophageal reflux disease, H. pylori infection, and chronic alcohol use.

d

Oral anticoagulant, aspirin, and clopidogrel.

e

Defined as age ≥50 years, and at least one of the following additional high-risk features: age ≥65 years, diabetes mellitus on medication, a prior spontaneous AMI, multivessel CAD, or chronic renal dysfunction (eGFR <60 ml/min/1.73 m²).

Maintenance antithrombotic strategy after ST-elevation myocardial infarction

AMI = acute myocardial infarction; CAD = coronary artery disease; DAPT = dual antiplatelet therapy; eGFR = estimated glomerular filtration rate; LV = left ventricular; PCI = percutaneous coronary intervention; PPI = proton pump inhibitor; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

c

History of gastrointestinal bleeding, anticoagulant therapy, chronic non-steroidal anti-inflammatory drug/corticosteroid user, and ≥2 or more of the following: age ≥65 years, dyspepsia, gastro-oesophageal reflux disease, H. pylori infection, and chronic alcohol use.

d

Oral anticoagulant, aspirin, and clopidogrel.

e

Defined as age ≥50 years, and at least one of the following additional high-risk features: age ≥65 years, diabetes mellitus on medication, a prior spontaneous AMI, multivessel CAD, or chronic renal dysfunction (eGFR <60 ml/min/1.73 m²).

7.3 Beta-blockers

7.3.1 Early intravenous beta-blocker administration

In patients undergoing fibrinolysis, early i.v. beta-blocker treatment reduces the incidence of acute malignant ventricular arrhythmias, although there is no clear evidence of long-term clinical benefit. ^344–346

In patients undergoing primary PCI, the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial (n = 270) showed that the very early administration of i.v. metoprolol (15 mg) at the time of diagnosis in patients with anterior STEMI, no signs of heart failure, and SBP >120 mmHg was associated with a reduction in infarct size measured by CMR at 5–7 days (25.6 g vs. 32.0 g; P = 0.012), and higher LVEF at 6 months CMR (48.7% vs. 45.0%; P = 0.018) compared with control treatment. ^{347 , 348} All patients without contraindications received oral metoprolol within 24 h. The incidence of MACE (composite of death, admission as a result of heart failure, reinfarction, or malignant ventricular arrhythmias) at 2 years was 10.8% vs. 18.3% in the i.v. metoprolol and control arms (P = 0.065). ³⁴⁸ Metoprolol treatment was associated with a significant reduction in the incidence and extent of MVO. ³⁴⁹ The Early Intravenous Beta-Blockers in Patients With ST-Segment Elevation Myocardial Infarction Before Primary Percutaneous Coronary Intervention (EARLY-BAMI) trial randomized 683 patients with STEMI within 12 h of onset to i.v. metoprolol (5 mg at recruitment and an additional 5 mg immediately before PCI) or placebo. ³⁵⁰ All patients without contraindications received oral metoprolol within 12 h. Early i.v. metoprolol administration did not show any benefit in reducing CMR-based infarct size, the trial primary endpoint, available only in 342 patients (55%), or the level of cardiac biomarker release. Early i.v. metoprolol was associated with a borderline reduction of malignant ventricular arrhythmias (3.6% vs. 6.9%; P = 0.050). Patients treated with i.v. metoprolol showed no increased risk of haemodynamic instability, atrioventricular (AV) block, or MACE at 30 days. Post hoc analyses from primary PCI trials testing other hypotheses have suggested that early i.v. beta-blocker administration might be associated with a clinical benefit, but a selection bias cannot be excluded even after correction for imbalances in baseline characteristics. ^{351 , 352} Based on the current available evidence, early administration of i.v. beta-blockers at the time of presentation followed by oral beta-blockers should be considered in haemodynamically stable patients undergoing primary PCI.

7.3.2 Mid- and long-term beta-blocker treatment

The benefit of long-term treatment with oral beta-blockers after STEMI is well established, although most of the supporting data come from trials performed in the pre-reperfusion era. ³⁵³ A recent multicentre registry enrolling 7057 consecutive patients with AMI showed a benefit in terms of mortality reduction at a median follow-up of 2.1 years associated with beta-blocker prescription at discharge, although no relationship between dose and outcomes could be identified. ³⁵⁴ Using registry data, the impact of newly introduced beta-blocker treatment on cardiovascular events in 19 843 patients with either ACS or undergoing PCI was studied. ³⁵⁵ At an average of 3.7 years of follow-up, the use of beta-blockers was associated with a significant mortality reduction (adjusted HR 0.90, 95% CI 0.84–0.96). The association between beta-blockers and outcomes differed significantly between patients with and without a recent MI (HR for death 0.85 vs. 1.02; P _int = 0.007). Opposing these results, in a longitudinal observational propensity-matched study including 6758 patients with previous MI, beta-blocker use was not associated with a lower risk of cardiovascular events or mortality. ³⁵⁶ Based on the current evidence, routine administration of beta-blockers in all post-STEMI patients should be considered as discussed in detail in the heart failure guidelines; ⁶ beta-blockers are recommended in patients with reduced systolic LV function (LVEF ≤40%), in the absence of contraindications such as acute heart failure, haemodynamic instability, or higher degree AV block. Agents and doses of proven efficacy should be administered. ^357–361 As no study has properly addressed beta-blocker duration to date, no recommendation in this respect can be made. Regarding the timing of initiation of oral beta-blocker treatment in patients not receiving early i.v. beta-blockade, a retrospective registry analysis on 5259 patients suggested that early (i.e. <24 h) beta-blocker administration conveyed a survival benefit compared with a delayed one. ³⁶² Therefore, in haemodynamically stable patients, oral beta-blocker initiation should be considered within the first 24 h.

7.4 Lipid-lowering therapy

The benefits of statins in secondary prevention have been unequivocally demonstrated, ³⁶³ and trials have shown the benefits of early and intensive statin therapy in ACS. ^{364 , 365} A meta-analysis of trials comparing more- vs. less-intensive LDL-C lowering with statins indicated that more-intensive statin therapy produced greater reductions in the risks of cardiovascular death, non-fatal MI, ischaemic stroke, and coronary revascularization. ³⁶⁶ For every 1.0 mmol/L reduction in LDL-C, these further reductions in risk were similar to the proportional reductions in the trials of statins vs. control. Therefore, statins are recommended in all patients with AMI, irrespective of cholesterol concentration at presentation. Lipid-lowering treatment should be started as early as possible, as this increases patient adherence after discharge, and given as high-intensity treatment, as this is associated with early and sustained clinical benefits. ⁴ The intensity of statin therapy should be increased in those receiving a low- or moderate-intensity statin treatment at presentation, unless they have a history of intolerance to high-intensity statin therapy or other characteristics that may influence safety. ^366–368 The treatment goal is an LDL-C concentration of < 1.8 mmol/L (<70 mg/dL) or at least 50% reduction in LDL-C if the baseline LDL-C level is 1.8–3.5 mmol/L. ^{4 , 367 , 369} The use of lower-intensity statin therapy should be considered in patients at increased risk of side effects from statins (e.g. elderly, hepatic or renal impairment, previous side effects, or a potential for interaction with essential concomitant therapy). Following MI, the lipid profile goes through phasic changes, with small reductions in total cholesterol, LDL-C, and HDL-C, and increases in triglycerides within the first 24 h. ^{370 , 371} A lipid profile should be obtained as early as possible after admission for STEMI and can be non-fasting, as total and HDL-C show little diurnal variation and LDL-C variation is within 10%. ³⁷² Lipids should be re-evaluated 4–6 weeks after the ACS to determine whether the target levels have been reached and regarding safety issues; the lipid lowering therapy can then be adjusted accordingly. Trial results with high doses of atorvastatin and simvastatin ^{366 , 373–375} favour a high-intensity statin.

In patients known to be intolerant of any dose of statin, treatment with ezetimibe should be considered. In the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), 18 144 patients with a recent ACS (29% with STEMI) were randomized to either ezetimibe 10 mg/simvastatin 40 mg or simvastatin 40 mg alone (simvastatin was up-titrated to 80 mg if LDL-C was >79 mg/dL or 2.04 mmol/L). ³⁷⁶ Over a period of 7 years, the composite primary endpoint of cardiovascular death, MI, hospital admission for unstable angina, coronary revascularization, or stroke was significantly lower in the combined treatment arm compared with the statin-only arm (32.7% vs. 34.7%; HR 0.94, 95% CI 0.89–0.99).

Recent data from phase I–III trials show that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors decrease LDL-C up to 60%, either as monotherapy or in addition to a statin dose, and also have beneficial effects on triglycerides and HDL-C. ^377–380 Meta-analyses of existing trials with more than 10 000 patients indicate a significant mortality benefit (HR 0.45, 95% CI 0.23–0.86) but are based on relatively few endpoints. ^{378 , 381} In the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial consisting of 27 564 patients with atherosclerotic cardiovascular disease, additional risk factors, and LDL ≥70 mg/dL (1.8 mmol/L), who were already receiving moderate or high intensity statin therapy as compared to placebo, evolocumab injections reduced the primary composite endpoint of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization by 15% in relative rate and by 1.5% in absolute rate. There were no differences in all-cause mortality or cardiovascular mortality and no significant differences in adverse events. ³⁸² Given the moderate effect over 2 years and the absence of mortality reduction, its use should still be restricted to selected high-risk patients.

Based on this relatively limited body of evidence, clinicians should consider adding a non-statin treatment to patients at high risk who do not reach treatment targets after STEMI despite the maximum tolerated dose of statin.

7.5 Nitrates

The routine use of nitrates in STEMI was of no benefit in a randomized controlled trial against placebo and is therefore not recommended. ³⁸³ Intravenous nitrates may be useful during the acute phase in patients with hypertension or heart failure, provided there is no hypotension, RV infarction, or use of phosphodiesterase type 5 inhibitors in the previous 48 h. Following the acute phase, nitrates remain valuable agents to control residual angina symptoms.

7.6 Calcium antagonists

A meta-analysis of 17 trials involving calcium antagonists early in the course of STEMI showed no beneficial effect on death or reinfarction, with a trend of higher mortality for patients treated with nifedipine. Therefore, routine use of calcium antagonists in the acute phase is not indicated. ^{384 , 385} In the chronic phase, a randomized controlled trial allocating 1775 patients with MI not on beta-blockers to verapamil or placebo found that the risk of mortality and reinfarction was reduced with verapamil. ³⁸⁶ Thus, in patients with contraindications to beta-blockers, particularly in the presence of obstructive airway disease, calcium antagonists are a reasonable option for patients without heart failure or impaired LV function. Routine use of dihydropyridines, on the other hand, has failed to show benefit after STEMI, ³⁸⁷ and they should therefore only be prescribed for clear additional indications such as hypertension or residual angina. ³⁸⁸

7.7 Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers

ACE inhibitors are recommended in patients with an impaired LVEF (≤40%) or who have experienced heart failure in the early phase. ^{383 , 389–392} A systematic overview of trials of ACE inhibition early in STEMI indicated that this therapy is safe, well tolerated, and associated with a small but significant reduction in 30-day mortality, with most of the benefit observed in the first week. ^{383 , 393} Treatment with ACE inhibitors is recommended in patients with systolic LV dysfunction or heart failure, hypertension, or diabetes, and should be considered in all STEMI patients. ^{394 , 395} Patients who do not tolerate an ACE inhibitor should be given an angiotensin II receptor blocker (ARB). In the context of STEMI, valsartan was found to be non-inferior to captopril in the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. ³⁹⁶

7.8 Mineralocorticoid/aldosterone receptor antagonists

Mineralocorticoid receptor antagonist (MRA) therapy is recommended in patients with LV dysfunction (LVEF ≤40%) and heart failure after STEMI. ^397–400 Eplerenone, a selective aldosterone receptor antagonist, has been shown to reduce morbidity and mortality in these patients. The Eplerenone Post-AMI Heart failure Efficacy and SUrvival Study (EPHESUS) randomized 6642 post-MI patients with LV dysfunction (LVEF ≤40%) and symptoms of heart failure/diabetes to eplerenone or placebo within 3–14 days after their infarction. ³⁹⁷ After a mean follow-up of 16 months, there was a 15% relative reduction in total mortality and a 13% reduction in the composite of death and hospitalization for cardiovascular events.

Two recent studies have indicated a beneficial effect of early treatment with MRA in the setting of STEMI without heart failure. The Double-Blind, Randomized, Placebo-Controlled Trial Evaluating The Safety And Efficacy Of Early Treatment With Eplerenone In Patients With Acute Myocardial Infarction (REMINDER) trial randomized 1012 patients with acute STEMI without heart failure to eplerenone or placebo within 24 h of symptom onset. ⁴⁰¹ After 10.5 months, the primary combined endpoint [CV mortality, re-hospitalization, or extended initial hospital stay due to diagnosis of heart failure, sustained ventricular tachycardia or fibrillation, ejection fraction ≤40%, or elevated B-type natriuretic peptide (BNP)/N-terminal pro B-type natriuretic peptide (NT-proBNP)] occurred in 29.4% of the active group vs. 18.2% in the placebo group (P < 0.0001), with the difference primarily driven by BNP levels. ⁴⁰¹ The Aldosterone Lethal effects Blockade in Acute myocardial infarction Treated with or without Reperfusion to improve Outcome and Survival at Six months follow-up (ALBATROSS) trial randomized 1603 patients with acute STEMI or high-risk NSTEMI to a single i.v. bolus of potassium canrenoate (200 mg) followed by spironolactone (25 mg daily) vs. placebo. Overall, the study found no effect on the composite outcome (death, resuscitated cardiac arrest, significant ventricular arrhythmia, indication for implantable defibrillator, or new or worsening heart failure) at 6 months. In an exploratory analysis of the STEMI subgroup (n = 1229), the outcome was significantly reduced in the active treatment group (HR 0.20, 95% CI 0.06–0.70). ⁴⁰² Future studies will clarify the role of MRA treatment in this setting.

When using MRA, care should be taken with reduced renal function [creatinine concentration >221 mmol/L (2.5 mg/dL) in men and >177 mmol/L (2.0 mg/dL) in women] and routine monitoring of serum potassium is warranted.

Routine therapies in the acute, subacute, and long-term phases: beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, and lipid-lowering treatments after ST-elevation myocardial infarction

AV = atrioventricular; ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker; LDL-C = low-density lipoprotein cholesterol; LV = left ventricular; LVEF = left ventricular ejection fraction; MRA = mineralocorticoid receptor antagonist; PCI = percutaneous coronary intervention; SBP = systolic blood pressure; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

c

High-intensity statin defined as atorvastatin 40–80 mg and rosuvastatin 20–40 mg.

Routine therapies in the acute, subacute, and long-term phases: beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, and lipid-lowering treatments after ST-elevation myocardial infarction

AV = atrioventricular; ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker; LDL-C = low-density lipoprotein cholesterol; LV = left ventricular; LVEF = left ventricular ejection fraction; MRA = mineralocorticoid receptor antagonist; PCI = percutaneous coronary intervention; SBP = systolic blood pressure; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

c

High-intensity statin defined as atorvastatin 40–80 mg and rosuvastatin 20–40 mg.

Figures 5 and 6 present the mostly prescribed interventions (class I and IIa) in patients undergoing primary PCI or fibrinolysis strategies.

Figure 5

"Do not forget" interventions in STEMI patients undergoing a primary PCI strategy. ACE = angiotensin-converting enzyme; DAPT = dual antiplatelet therapy; DES = drug eluting stent; ECG = electrocardiogram; echo = echocardiogram; ED = emergency department; HF = heart failure; i.v. = intravenous; IRA = infarct related artery; LVEF = left ventricular ejection fraction; MRA = mineralcorticoid receptor antagonist; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction; UFH = Unfractionated heparin. Mostly prescribed interventions (class I, green, and IIa, yellow) are presented along with the expected timing of delivery. Solid lines represent recurrent (daily) intervention. Double-arrowed dashed lines represent a time-window in which the intervention can be delivered.

¹Aspirin loading dose: 150–300 mg chewed or 75–250 mg intravenous (in patients not already on an aspirin maintenance dose).

²Prasugrel loading dose: 60 mg. Ticagrelor loading dose: 180 mg. If there are contra-indications for prasugrel/ticagrelor or these are not available, a loading dose of clopidogrel (600 mg) is indicated.

³If the interventional cardiologist is not expert in radial access, the femoral route is then preferred.

⁴Enoxaparin or bivalirudin are alternatives to unfractionated heparin (Class IIa A).

⁵Aspirin maintenance dose: 75–100 mg oral.

⁶Prasugrel maintenance dose: 10 mg once daily. Ticagrelor maintenance dose: 90 mg twice daily. If there are contra-indications for prasugrel/ticagrelor or these are not available, clopidogrel maintenance (75 mg daily) is indicated.

^a90 min represents the maximum target time to PCI-mediated reperfusion. For patients presenting in a PCI-centre, this target time is 60 min.

^bProlongation of ticagrelor (60 mg twice daily) in addition to aspirin may be considered for up to 36 months in patients at high ischaemic risk who have tolerated DAPT without a bleeding complication.

Figure 5

"Do not forget" interventions in STEMI patients undergoing a primary PCI strategy. ACE = angiotensin-converting enzyme; DAPT = dual antiplatelet therapy; DES = drug eluting stent; ECG = electrocardiogram; echo = echocardiogram; ED = emergency department; HF = heart failure; i.v. = intravenous; IRA = infarct related artery; LVEF = left ventricular ejection fraction; MRA = mineralcorticoid receptor antagonist; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction; UFH = Unfractionated heparin. Mostly prescribed interventions (class I, green, and IIa, yellow) are presented along with the expected timing of delivery. Solid lines represent recurrent (daily) intervention. Double-arrowed dashed lines represent a time-window in which the intervention can be delivered.

¹Aspirin loading dose: 150–300 mg chewed or 75–250 mg intravenous (in patients not already on an aspirin maintenance dose).

²Prasugrel loading dose: 60 mg. Ticagrelor loading dose: 180 mg. If there are contra-indications for prasugrel/ticagrelor or these are not available, a loading dose of clopidogrel (600 mg) is indicated.

³If the interventional cardiologist is not expert in radial access, the femoral route is then preferred.

⁴Enoxaparin or bivalirudin are alternatives to unfractionated heparin (Class IIa A).

⁵Aspirin maintenance dose: 75–100 mg oral.

⁶Prasugrel maintenance dose: 10 mg once daily. Ticagrelor maintenance dose: 90 mg twice daily. If there are contra-indications for prasugrel/ticagrelor or these are not available, clopidogrel maintenance (75 mg daily) is indicated.

^a90 min represents the maximum target time to PCI-mediated reperfusion. For patients presenting in a PCI-centre, this target time is 60 min.

^bProlongation of ticagrelor (60 mg twice daily) in addition to aspirin may be considered for up to 36 months in patients at high ischaemic risk who have tolerated DAPT without a bleeding complication.

Figure 6

"Do not forget" interventions in STEMI patients undergoing a successful fibrinolysis strategy. ACE = angiotensin-converting enzyme; DAPT = dual antiplatelet therapy; DES = drug eluting stent; ECG = electrocardiogram; echo = echocardiogram; HF = heart failure; i.v. = intravenous; IRA = infarct related artery; LVEF = left ventricular ejection fraction; MRA = mineralcorticoid receptor antagonist; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction; UFH = Unfractionated heparin. Mostly prescribed interventions (class I, green, and IIa, light yellow) are presented along with the expected timing of delivery. Solid lines represent recurrent (daily) intervention. Double-arrowed dashed lines represent a time-window in which the intervention can be delivered.

¹Enoxaparin dose: 30 mg i.v. bolus followed by 1 mg/kg subcutaneous every 12 hours (dose adjustment for ≥75 years and renal insufficiency is presented in Table 9). Unfractionated heparin is an alternative to enoxaparin.

²Aspirin loading dose: 150–300 mg chewed or 75–250 mg intravenous.

³Clopidogrel loading dose: 300 mg oral (75 mg in ≥ 75 years).

⁴Aspirin maintenance dose: 75–100 mg oral

⁵Clopidogrel maintenance therapy: 75 mg daily.

⁶48 hours after fibrinolysis, switch to prasugrel/ticagrelor may be considered in PCI-treated patients.

Figure 6

"Do not forget" interventions in STEMI patients undergoing a successful fibrinolysis strategy. ACE = angiotensin-converting enzyme; DAPT = dual antiplatelet therapy; DES = drug eluting stent; ECG = electrocardiogram; echo = echocardiogram; HF = heart failure; i.v. = intravenous; IRA = infarct related artery; LVEF = left ventricular ejection fraction; MRA = mineralcorticoid receptor antagonist; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction; UFH = Unfractionated heparin. Mostly prescribed interventions (class I, green, and IIa, light yellow) are presented along with the expected timing of delivery. Solid lines represent recurrent (daily) intervention. Double-arrowed dashed lines represent a time-window in which the intervention can be delivered.

¹Enoxaparin dose: 30 mg i.v. bolus followed by 1 mg/kg subcutaneous every 12 hours (dose adjustment for ≥75 years and renal insufficiency is presented in Table 9). Unfractionated heparin is an alternative to enoxaparin.

²Aspirin loading dose: 150–300 mg chewed or 75–250 mg intravenous.

³Clopidogrel loading dose: 300 mg oral (75 mg in ≥ 75 years).

⁴Aspirin maintenance dose: 75–100 mg oral

⁵Clopidogrel maintenance therapy: 75 mg daily.

⁶48 hours after fibrinolysis, switch to prasugrel/ticagrelor may be considered in PCI-treated patients.

Figure 7

Diagnostic test flow chart in MINOCA. CMR = Cardiac Magnetic Resonance; IVUS = IntraVascular UltraSound; LV = Left Ventricle; MINOCA = Myocardial Infarction with Non-Obstructed Coronary Arteries; OCT = Optical Coherence Tomography; STEMI = ST segment Elevation Myocardial Infarction; TOE = Trans-Oesofageal Echocardiography; TTE = Trans-Thoracic Echocardiography. Takotsubo syndrome cannot be diagnosed with certainty in the acute phase as the definition requires follow up imaging to document recovery of left ventricular function. IVUS and OCT frequently show more atherosclerotic plaque than may be appreciated on angiography. They also increase sensitivity for dissection. If intracoronary imaging is to be performed, it is appropriate to carry out this imaging at the time of the acute cardiac catheterization, after diagnostic angiography. Patients should be made aware of the additional information the test can provide and the small increase in risk associated with intracoronary imaging.

1 • Provocative testing for coronary artery spasm might be considered in selected patients with a recent AMI with suspected vasospastic angina. Provocative manoeuvres have to be always performed by operators with experience and not necessarily in the acute phase of STEMI.

2 • Clinically suspected myocarditis by ESC Task Force criteria = No angiographic stenosis ≥50% plus non ischemic pattern on CMR.

Definite myocarditis by ESC Task Force criteria = No angiographic stenosis ≥50% plus endomyocardial biopsy confirmation (histology, immunohistology, polymerase-chain reaction based techniques to search for genome of infectious agents, mainly viruses).

Figure 7

Diagnostic test flow chart in MINOCA. CMR = Cardiac Magnetic Resonance; IVUS = IntraVascular UltraSound; LV = Left Ventricle; MINOCA = Myocardial Infarction with Non-Obstructed Coronary Arteries; OCT = Optical Coherence Tomography; STEMI = ST segment Elevation Myocardial Infarction; TOE = Trans-Oesofageal Echocardiography; TTE = Trans-Thoracic Echocardiography. Takotsubo syndrome cannot be diagnosed with certainty in the acute phase as the definition requires follow up imaging to document recovery of left ventricular function. IVUS and OCT frequently show more atherosclerotic plaque than may be appreciated on angiography. They also increase sensitivity for dissection. If intracoronary imaging is to be performed, it is appropriate to carry out this imaging at the time of the acute cardiac catheterization, after diagnostic angiography. Patients should be made aware of the additional information the test can provide and the small increase in risk associated with intracoronary imaging.

1 • Provocative testing for coronary artery spasm might be considered in selected patients with a recent AMI with suspected vasospastic angina. Provocative manoeuvres have to be always performed by operators with experience and not necessarily in the acute phase of STEMI.

2 • Clinically suspected myocarditis by ESC Task Force criteria = No angiographic stenosis ≥50% plus non ischemic pattern on CMR.

Definite myocarditis by ESC Task Force criteria = No angiographic stenosis ≥50% plus endomyocardial biopsy confirmation (histology, immunohistology, polymerase-chain reaction based techniques to search for genome of infectious agents, mainly viruses).

8. Complications following ST-segment elevation myocardial infarction

Expanded information about complications following STEMI is presented in the Web Addenda.

8.1 Myocardial dysfunction

8.1.1 Left ventricular dysfunction

See Web Addenda.

8.1.2 Right ventricular involvement

See Web Addenda.

8.2 Heart failure

8.2.1 Clinical presentations

See Web Addenda.

8.2.2 Management

Patients with heart failure should be under continuous monitoring of heart rhythm, blood pressure, and urinary output. The mechanism of heart failure should be assessed early by physical examination, ECG, echocardiography, and (when not rapidly controlled) with invasive haemodynamic monitoring, and corrected as soon as possible.

Patients with pulmonary congestion and SaO₂ <90% or partial pressure of oxygen (PaO₂) <60 mmHg (8.0 kPa) require oxygen therapy and SaO₂ monitoring to correct hypoxaemia, with a target of 95%, and may require periodic blood-gas assessment. Initial pharmacological treatment includes i.v. loop diuretics (e.g. furosemide 20–40 mg i.v. with repeated doses at intervals as needed according to clinical evolution and diuresis) and, if blood pressure allows it, i.v. nitrates, avoiding hypotension or excessive falls in blood pressure. The early use of beta-blockers, ACE inhibitors/ARBs, and MRA is recommended in the absence of hypotension, hypovolaemia, or renal dysfunction. Causal treatment is essential. Coronary revascularization should be performed early when significant CAD is still present. Rhythm disturbances, valvular dysfunction, and hypertension should be corrected as soon as possible. Hypertension should be treated promptly with oral ACE inhibitors/ARBs and i.v. nitrates. In very severe cases, sodium nitroprusside infusion may be necessary. Persistent myocardial ischaemia should be treated with early coronary revascularization. Atrial and ventricular dysrhythmias, and valvular dysfunction or mechanical complications, should be treated as appropriate (see specific sections in this document).

Severely symptomatic patients with pulmonary congestion may also need i.v. morphine to reduce dyspnoea and anxiety, but routine use is not recommended due to concerns about its safety, as it may induce nausea and hypopnea. ^{408 , 409} Non-invasive positive pressure ventilation (continuous positive airway pressure, biphasic positive airway pressure) or high-flow nasal cannula is effective in treating pulmonary oedema and should be considered in patients with respiratory distress (respiratory rate >25 breaths/min, SaO₂ <90%) and started soon. ^{410 , 411} Endotracheal intubation and ventilatory support may be required in patients unable to achieve adequate oxygenation, or in those with excess respiratory work or evidence of hypercapnia due to respiratory exhaustion. Ultrafiltration to reduce fluid overload may be considered in patients who are refractory to diuretics, especially in patients with hyponatraemia.

In patients with heart failure and adequate blood pressure (SBP >90 mmHg), but a severe reduction in cardiac output resulting in compromised vital organ perfusion not responding to standard therapy, treatment with dobutamine or levosimendan may be considered. However, the clinical evidence of levosimendan in cardiogenic shock is limited. Further details on the management of acute heart failure can be found in the 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. ⁶

Recommendations for the management of left ventricular dysfunction and acute heart failure in ST-elevation myocardial infarction

ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker; LV = left ventricular; LVEF = left ventricular ejection fraction; MRA = mineralocorticoid receptor antagonist; SaO₂ = arterial oxygen saturation; SBP = systolic blood pressure; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

Recommendations for the management of left ventricular dysfunction and acute heart failure in ST-elevation myocardial infarction

ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker; LV = left ventricular; LVEF = left ventricular ejection fraction; MRA = mineralocorticoid receptor antagonist; SaO₂ = arterial oxygen saturation; SBP = systolic blood pressure; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

8.2.2.1 Management of hypotension

In patients with hypotension and normal perfusion without evidence of congestion or volume overload (i.e. collapsible inferior vena cava), gentle volume loading should be attempted after ruling out complications such as mechanical or severe mitral regurgitation, with central pressure monitoring. Bradycardia or tachyarrhythmias should be corrected or controlled. In patients with RV infarction, volume overloading should be avoided because it might worsen haemodynamics. ⁴²⁰ If hypotension persists, inotropic therapy, preferably with dobutamine, may be considered. ⁴²⁰

8.2.2.2 Management of cardiogenic shock

Cardiogenic shock is defined as persistent hypotension (SBP <90 mmHg) despite adequate filling status with signs of hypoperfusion. It complicates 6–10% of all STEMI cases and remains a leading cause of death, with in-hospital mortality rates ≥50%. ⁴²¹ Shock is also considered to be present if i.v. inotropes and/or mechanical support are needed to maintain an SBP >90 mmHg. In STEMI patients presenting with cardiogenic shock in which PCI-mediated reperfusion is estimated to occur >120 min, immediate fibrinolysis and transfer to a PCI centre should be considered. In these cases, upon arrival at the PCI centre, emergent angiography is indicated, regardless of the ST resolution and the time from fibrinolysis administration. It is usually associated with extensive LV damage, but may occur in RV infarction. Cardiogenic shock characterization and management do not necessarily need invasive haemodynamic monitoring, but ventricular and valve function should be urgently evaluated by transthoracic echocardiography and associated mechanical complications ruled out. ^422–426

The first step in patients with cardiogenic shock is to identify the mechanism and to correct any reversible cause such as hypovolaemia, drug-induced hypotension, or arrhythmias; alternatively, initiate the treatment of potential specific causes, such as mechanical complications or tamponade.

Treatments include immediate reperfusion, with primary PCI whenever possible, ^{248 , 427} and complete revascularisation if multivessel disease is present. In addition, patients at the highest risk for development of shock might benefit from an early transfer to tertiary centres before the onset of haemodynamic instability. Antithrombotic therapy does not differ from that in any STEMI patient. The specificities of the management of low-output cardiogenic shock associated with RV infarction are mentioned in the Web Addenda.

Invasive monitoring with an arterial line is recommended. ⁶ A pulmonary artery catheter may be considered, in order to perform a careful adjustment of filling pressures and assessment of cardiac output or in cases of shock of unexplained cause. Hypovolaemia should be ruled out first and corrected with fluid loading. Pharmacological therapy aims to improve organ perfusion by increasing cardiac output and blood pressure. Diuretic therapy is recommended when adequate perfusion is attained. Intravenous inotropic agents or vasopressors are usually required to maintain an SBP >90 mmHg, and to increase cardiac output and improve vital organ perfusion. Dobutamine is the initial therapy for patients with predominant low cardiac output, whereas norepinephrine may be safer and more effective than dopamine in patients with cardiogenic shock and severe hypotension. ⁴²⁸ Levosimendan may be considered as an alternative, especially for patients on chronic beta-blocker therapy, because its inotropic effect is independent of beta-adrenergic stimulation. Phosphodiesterase III inhibitors are not recommended in STEMI patients.

IABP counterpulsation does not improve outcomes in patients with STEMI and cardiogenic shock without mechanical complications, ¹⁷⁷ nor does it significantly limit infarct size in those with potentially large anterior MIs. ¹⁷⁵ Therefore, routine IABP counterpulsation cannot be recommended, but may be considered for haemodynamic support in selected patients (i.e. severe mitral insufficiency or ventricular septal defect). A small exploratory trial studying the Impella CP percutaneous circulatory support device did not find any benefit compared with IABP in AMI complicated by cardiogenic shock. ⁴²⁹

Mechanical LV assist devices (LVADs), including percutaneous short-term mechanical circulatory support devices (i.e. intra-cardiac axial flow pumps and arterial-venous extracorporeal membrane oxygenation), have been used in patients not responding to standard therapy, including inotropes, fluids, and IABP, but evidence regarding their benefits is limited. ⁴³⁰ Therefore, short-term mechanical circulatory support may be considered as a rescue therapy in order to stabilize the patients and preserve organ perfusion (oxygenation) as a bridge to recovery of myocardial function, cardiac transplantation, or even LV assist device destination therapy on an individual basis. ^{431 , 432}

Recommendations for the management of cardiogenic shock in ST-elevation myocardial infarction

CABG = coronary artery bypass graft surgery; ECLS = extracorporeal life support; ECMO = extracorporeal membrane oxygenation; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

c

Percutaneous cardiac support devices, ECLS, and ECMO.

Recommendations for the management of cardiogenic shock in ST-elevation myocardial infarction

CABG = coronary artery bypass graft surgery; ECLS = extracorporeal life support; ECMO = extracorporeal membrane oxygenation; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

c

Percutaneous cardiac support devices, ECLS, and ECMO.

8.3 Management of arrhythmias and conduction disturbances in the acute phase

Arrhythmias and conduction disturbances are common during the early hours of STEMI and are also important prognostic factors. ⁴³⁸ Despite increased awareness and improved basic and advanced life support, the incidence of sudden cardiac death, mainly due to fast ventricular tachycardia (VT) and VF in the pre-hospital phase, remains high. ^{438 , 439} Early reperfusion therapy reduces the risk of ventricular arrhythmias and cardiovascular death. ^{440 , 441} The presence of life-threatening arrhythmias requires an urgent need for a fast and complete revascularization in STEMI. ^{438 , 442} The evidence for benefits of antiarrhythmic drugs in STEMI patients is limited and negative effects of antiarrhythmic drugs on early mortality have been demonstrated. ⁴³⁹ Careful use of antiarrhythmic drugs is generally recommended and alternative treatment options such as electrical cardioversion, a 'wait and see' strategy for arrhythmias with no or moderate haemodynamic relevance, or in selected cases cardiac pacing and catheter ablation, should be considered. Correction of electrolyte imbalances and early treatment with beta-blockers, ACE inhibitors/ARBs, and statins is recommended. ^{438 , 443}

8.3.1 Supraventricular arrhythmias

The most frequent supraventricular arrhythmia is AF, with up to 21% of STEMI patients affected. ⁴⁴⁴ AF may be pre-existing, first-time detected, or of new onset. Patients with AF have more comorbidities and are at higher risk for complications. ⁴⁴⁵ In many cases, the arrhythmia is well tolerated and no specific treatment is required, other than anticoagulation. ⁵ Prompt treatment is required in acute haemodynamic instability. There is scarce information indicating preferences for rate control over rhythm control in this situation. ⁴⁴⁶ Electrical cardioversion should be considered but early recurrence of AF is frequent after successful cardioversion. Acute rhythm control with antiarrhythmic drugs is limited to the use of amiodarone. ^{5 , 444} Adequate rate control can be accomplished by administration of beta-blockers. ^{438 , 446} In patients with extensive myocardial damage or severe LV dysfunction, rate control is more safely achieved with i.v. digoxin with or without concomitant administration of i.v. amiodarone. When co-administering i.v. digoxin and amiodarone, close monitoring for digoxin toxicity is necessary as digoxin serum concentrations may be increased. Several, but not all, studies have suggested that new-onset AF may be reduced by beta-blockers, ACE inhibitors/ARBs, and also early-onset statin therapy. ⁴⁴⁴ Patients with AF and risk factors for thromboembolism should be adequately treated with chronic oral anticoagulation. ⁵ STEMI patients with documented AF have worse short- and long-term prognoses when compared with patients in sinus rhythm. ^{445 , 447} Presence of AF is associated with a higher reinfarction rate, higher stroke rate, higher risk for heart failure, and may also increase the risk for sudden cardiac death. ^{444 , 445 , 448} Of note, also transient, self-terminating AF during STEMI relates to a significantly higher stroke rate during long-term follow-up. ^{445 , 448}

Management of atrial fibrillation

AF = atrial fibrillation; CHA₂DS₂-VASc = Cardiac failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled) – VAScular disease, Age 65–74 and Sex category (Female); STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

Management of atrial fibrillation

AF = atrial fibrillation; CHA₂DS₂-VASc = Cardiac failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled) – VAScular disease, Age 65–74 and Sex category (Female); STEMI = ST-segment elevation myocardial infarction.

a

Class of recommendation.

b

Level of evidence.

8.3.2 Ventricular arrhythmias

The incidence of VT and VF has declined over recent decades, most probably due to the uptake of reperfusion strategies and the early use of beta-blockers. ³ However, 6–8% of patients still develop haemodynamically significant VT or VF during this phase. ⁴³⁹ The typical arrhythmia presentation is unstable, frequently polymorphic, and relatively fast VT, often degenerating into VF. Urgent reperfusion is most important as ischaemia often triggers these arrhythmias. ⁷² Beta-blockers are recommended if no contraindications exist. ^{346 , 347 , 350 , 454} Repetitive electrical cardioversion or defibrillation may be necessary. ⁴⁵⁵ If there is no sufficient control, i.v. administration of amiodarone is recommended. ^{439 , 456} In case of contraindications to amiodarone, i.v. lidocaine may be considered, although no studies comparing superiority of either drug in STEMI patients are available. The prognostic role of early VT/VF within the first 48 h of STEMI is still controversial. Available data suggest that patients with early VT/VF have increased 30-day mortality but no increased long-term arrhythmic risks. ^{442 , 457 , 458}

VT or VF may occur at the time of restoration of coronary blood flow (reperfusion arrhythmias). No specific antiarrhythmic drug therapy is necessary due to the benign long-term course. Ventricular premature beats are very frequent on the first day of the acute phase and complex arrhythmias (multiform complexes, short runs, or the R-on-T phenomenon) are common. Their value as predictors of VF is questionable and no specific therapy is required. Sustained VT or VF outside the early phase (usually 48 h after STEMI onset) not triggered by recurrent ischaemia has a poor prognostic implication, and evaluation for ICD implantation for secondary prevention of sudden cardiac death is recommended according to current guidelines. ³ Primary prevention of sudden cardiac death with the ICD within 40 days after MI in the absence of VT/VF is generally not indicated. ³ Patients should be re-evaluated for ICD implantation 6–12 weeks after revascularization, although those with pre-existing impaired LVEF may be considered for ICD implantation for primary prevention even within the early post-infarction period. ^{3 , 438}

Some patients may develop electrical storm and/or incessant VT despite complete revascularization and treatment with antiarrhythmic drugs. Overdrive stimulation may help to control this situation; however, recurrence of VT/VF upon cessation of stimulation is frequent and catheter ablation of such triggers appears to be the only treatment option. Successful radiofrequency ablation has been shown to abolish recurrent VT/VF. ^459–461

Management of ventricular arrhythmias and conduction disturbances in the acute phase

AV = atrioventricular; i.v. = intravenous; ICD = implantable cardioverter defibrillator; VF = ventricular fibrillation; VT = ventricular tachycardia.

a

Class of recommendation.

b

Level of evidence.

Management of ventricular arrhythmias and conduction disturbances in the acute phase

AV = atrioventricular; i.v. = intravenous; ICD = implantable cardioverter defibrillator; VF = ventricular fibrillation; VT = ventricular tachycardia.

a

Class of recommendation.

b

Level of evidence.

Long-term management of ventricular arrhythmias and risk evaluation for sudden death

ICD = implantable cardioverter defibrillator; LVEF = left ventricular ejection fraction; MI = myocardial infarction; NYHA = New York Heart Association; STEMI = ST-segment elevation myocardial infarction; VF = ventricular fibrillation; VT = ventricular tachycardia.

a

Class of recommendation.

b

Level of evidence.

Long-term management of ventricular arrhythmias and risk evaluation for sudden death

ICD = implantable cardioverter defibrillator; LVEF = left ventricular ejection fraction; MI = myocardial infarction; NYHA = New York Heart Association; STEMI = ST-segment elevation myocardial infarction; VF = ventricular fibrillation; VT = ventricular tachycardia.

a

Class of recommendation.

b

Level of evidence.

8.3.3 Sinus bradycardia and atrioventricular block

Sinus bradycardia is common in the first hours of STEMI, especially in inferior MI. In some cases, opioids are responsible. ⁴⁶⁸ It often requires no treatment. If accompanied by severe hypotension, sinus bradycardia should be treated with i.v. atropine. Second-degree type I (Mobitz I or Wenckebach) AV block is usually associated with inferior wall MI and seldom causes adverse haemodynamic effects. If so, atropine should be used first; if it fails, pacing should be instituted. Agents that slow AV conduction (such as beta-blockers, digitalis, verapamil, or amiodarone) should be used with caution. Second-degree type II (Mobitz II) AV block and complete AV block may be indications for pacing. AV sequential pacing should be considered in patients with complete AV block, RV infarction, and haemodynamic compromise. Revascularization should be considered in patients with AV block who have not yet received reperfusion therapy (e.g. late arrival).

AV block associated with inferior wall infarction is usually supra-Hisian and usually resolves spontaneously or after reperfusion. AV block associated with anterior wall MI is usually infra-Hisian and has a high mortality rate due to the extensive myocardial necrosis. The development of a new bundle branch block or hemiblock usually indicates extensive anterior MI. A transvenous pacing electrode should be inserted in the presence of advanced AV block with a low escape rhythm, as described above, and considered if bifascicular or trifascicular block develops. Indications for pacing are outlined in detail in the ESC Guidelines for cardiac pacing and cardiac resynchronization therapy. ⁴⁶⁹

8.4 Mechanical complications

Mechanical complications may occur in the first days following STEMI, although incidence has fallen significantly in the era of primary PCI. Mechanical complications are life-threatening and need prompt detection and management. Sudden hypotension, recurrence of chest pain, new cardiac murmurs suggestive of mitral regurgitation or ventricular septal defect, pulmonary congestion, or jugular vein distension should raise suspicion. Immediate echocardiographic assessment is needed when mechanical complications are suspected. A full section describing mechanical complications can be found in the Web Addenda.

8.4.1 Free wall rupture

See Web Addenda.

8.4.2 Ventricular septal rupture

See Web Addenda.

8.4.3 Papillary muscle rupture

See Web Addenda.

8.5 Pericarditis

Three major pericardial complications may occur: early infarct-associated pericarditis, late pericarditis or post-cardiac injury (Dressler syndrome), and pericardial effusion. These are expanded upon in the Web Addenda.

8.5.1 Early and late (Dressler syndrome) infarct-associated pericarditis

See Web Addenda.

8.5.2 Pericardial effusion

See Web Addenda.

9. Myocardial infarction with non-obstructive coronary arteries

A sizeable proportion of MIs, ranging between 1–14%, occur in the absence of obstructive (>50% stenosis) CAD. ^{10 , 11} The demonstration of non-obstructive (<50%) CAD in a patient presenting with symptoms suggestive of ischaemia and ST-segment elevation or equivalent does not preclude an atherothrombosis aetiology, as thrombosis is a very dynamic phenomenon and the underlying atherosclerotic plaque can be non-obstructive.

The diagnostic criteria of MINOCA are presented in Table 10. MINOCA is a working diagnosis and should lead the treating physician to investigate underlying causes. Failure to identify the underlying cause may result in inadequate and inappropriate therapy in these patients.

Table 10

Diagnostic criteria for myocardial infarction with non-obstructive coronary arteries (adapted from Agewall et al ¹² )

AMI = acute myocardial infarction; IRA = infarct-related artery; MINOCA = myocardial infarction with non-obstructive coronary arteries.

Table 10

Diagnostic criteria for myocardial infarction with non-obstructive coronary arteries (adapted from Agewall et al ¹² )

AMI = acute myocardial infarction; IRA = infarct-related artery; MINOCA = myocardial infarction with non-obstructive coronary arteries.

The description of the pathophysiology of the different aetiological entities leading to MINOCA is beyond the scope of the present document, and has been extensively described and defined in position papers from the ESC ¹² and in dedicated review papers. ^{10 , 11} MINOCA patients can fulfil the criteria for both MI type 1 and type 2 according to the universal definition of MI. ⁸ There are disparate aetiologies causing MINOCA and they can be grouped into: (1) secondary to epicardial coronary artery disorders (e.g. atherosclerotic plaque rupture, ulceration, fissuring, erosion, or coronary dissection with non-obstructive or no CAD) (MI type 1); (2) imbalance between oxygen supply and demand (e.g. coronary artery spasm and coronary embolism) (MI type 2); (3) coronary endothelial dysfunction (e.g. microvascular spasm) (MI type 2); and (4) secondary to myocardial disorders without involvement of the coronary arteries (e.g. myocarditis ⁴⁷⁰ or Takotsubo syndrome). The last two entities may mimic MI but are better classified as myocardial injury conditions. The identification of the underlying cause of MINOCA should lead to specific treatment strategies. Although the outcome of MINOCA strongly depends on the underlying cause, its overall prognosis is serious, with a 1 year mortality of about 3.5%. ¹⁰

To determine the cause of MINOCA, the use of additional diagnostic tests beyond coronary angiography is recommended. In general, after ruling out obstructive CAD in a patient presenting with STEMI, an LV angiogram or echocardiography should be considered in the acute setting to assess wall motion or pericardial effusion. In addition, if any of the possible aetiologies described above is suspected, additional diagnostic tests may be considered.

CMR is a very helpful imaging technique due to its unique non-invasive tissue characterization, allowing the identification of wall motion abnormalities, presence of oedema, and myocardial scar/fibrosis presence and pattern. Performance of CMR within 2 weeks after onset of symptoms should be considered to increase the diagnostic accuracy of the test for identifying the aetiological cause of MINOCA. ^471–473

10. Assessment of quality of care

There is a wide practice gap between optimal and actual care for patients with STEMI in hospitals around the world. ^{474 , 475} To reduce this gap and improve quality of care, it is recommended that STEMI networks and their individual components establish measurable quality indicators, systems to measure and compare these indicators, perform routine audits, and implement strategies to ensure that every patient with STEMI receives the best possible care according to accepted standards and has the best possible outcomes (see Web Addenda). Quality indicators are intended to measure and compare the quality of health service provision and serve as a foundation for quality improvement initiatives. ⁴⁷⁶ Proposed quality indicators to assess the quality of the care for patients are presented in Table 11.

Table 11

Quality indicators

ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker; DAPT = dual antiplatelet therapy; ECG = electrocardiogram; GRACE = Global Registry of Acute Coronary Events; IRA = Infarct-related artery; LVEF = left ventricular ejection fraction; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

Table 11

Quality indicators

ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker; DAPT = dual antiplatelet therapy; ECG = electrocardiogram; GRACE = Global Registry of Acute Coronary Events; IRA = Infarct-related artery; LVEF = left ventricular ejection fraction; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

Expanded text about quality indicators can be found in the Web Addenda.

11. Gaps in the evidence and areas for future research

Despite the great advances in STEMI management over recent decades, important areas of uncertainty persist that should be explored in the future. Here, we identify some, but not all, specific areas that should be addressed within the next few years.

Public awareness and emergency care

The very early stages of STEMI are the most vulnerable time, when most sudden cardiac deaths occur. Public campaigns aiming to increase early alerting of patients with ischaemic symptoms should clearly state that the safest way to alert is to call the EMS. While selected centres and geographic areas have made great progress in ensuring high-quality rapid care for STEMI patients with routine pre-alert of the interventional team, there remains a need for streamlining of (pre-)hospital management in a homogeneous fashion worldwide, including rural areas. Educational programmes and cross-country exchange of experiences should help in this matter.

The selection of a 120 min from STEMI diagnosis to PCI-mediated reperfusion as the cut-off to choose PCI or fibrinolysis is based on relatively old registries and trials with different treatment strategies from those presented in this document. The identification of the best cut-off timing to choose a strategy is of extreme importance.

Reduction of ischaemia/reperfusion injury

Final infarct size is one of the best predictors of long-term adverse events in STEMI survivors. The introduction of a specific infarct-limiting therapy in clinical practice might have a massive clinical and socioeconomic impact. Several strategies, including pharmacological and mechanical therapies, have shown a reduction of infarct size by reducing ischaemia/reperfusion injury (including MVO) in experimental and small-scale clinical trials, but to date no large trial has demonstrated a clinical benefit. One potential reason for this poor translation is the difficulty of securing funds to conduct proper large-scale clinical trials in this context.

Refinement of (acute and long-term) antithrombotic regimes

Antithrombotic therapy is the cornerstone of the pharmacological approach in STEMI. Despite major recent advances, important questions remain unaddressed. What is the best acute and maintenance antithrombotic regimen in patients who have an indication for oral anticoagulants? What is the best timing for the loading dose of oral P2Y₁₂ inhibitors and what are the best strategies for i.v. antithrombotic therapies? What is the role of potent P2Y₁₂ inhibitors in patients undergoing fibrinolysis? What is the real role of aspirin in this new era of potent antiplatelet agents and low dose anticoagulation? What is the best duration of maintenance therapy with P2Y₁₂ inhibitors as single or multiple antithrombotic regimens?

Beta-blockers and ACE inhibitors

Although research regarding these classes of drugs was intense several decades ago, more recently, there has been a lack of properly powered clinical trials. The best timing for initiation (and route of administration) of beta-blockers is still not well established. The role of maintenance beta-blocker therapy is well established for patients with heart failure and/or low LVEF, but its clinical value for the rest of STEMI has not been prospectively tested in dedicated clinical trials of reperfused patients. Similar limitations apply to the use of maintenance ACE inhibitors.

Post-STEMI risk stratification

The optimal therapeutic strategy to minimize the risk of sudden death in patients who develop VT or VF during or early after STEMI is not entirely clear. Despite the clinical benefit of ICDs in patients with low LVEF and reduced functional class weeks after STEMI being well established, there is a need for better sudden death risk stratification algorithms.

The best management of non-IRA lesions should be addressed. Unresolved issues are the best criteria to guide PCI (angiography, FFR, or assessment of plaque vulnerability) and the best timing for complete revascularization if indicated (during index PCI or staged, including staged during hospitalization vs. after discharge).

Shock and left ventricular assist devices

Severe heart failure and shock are among the most important negative prognostic predictors in patients with STEMI. In addition to urgent revascularization of IRA and standard medical therapies for pre- and afterload reduction, there is limited evidence for the systematic use of inotropic and vasopressor agents as well as mechanical support. Similarly, the benefit of routine complete revascularization during the index PCI procedure has not been formally demonstrated. The use of IABP has not met prior expectations of benefit, while LV assist devices and ECMO are increasingly popular but have not been sufficiently evaluated in clinical trials. Systematic evaluation of pharmacological and interventional strategies and LV assist devices for patients with shock are urgently needed.

Myocardial repair/rescue

The effectiveness and safety of novel therapies able to replace dead myocardium or prevent poor remodelling (e.g. cell therapy or gene therapy) is an unfulfilled promise. There is a strong need for basic research studies to better understand the biological processes involved in cardiac development and repair, in order for there to be strong grounds to translate studies into clinically relevant animal models and finally into humans.

Need for observational data and real-world evidence

In order to understand shortcomings and challenges in clinical practice, for quality assessment and for benchmarking, unselected and validated registries and clinical databases are needed. In this document, we have specified quality indicators intended to measure and compare the quality of health service provision and serve as a foundation for quality improvement initiatives. Their effects on procedural and clinical outcomes need to be evaluated.

Need for pragmatic real-life clinical trials

One major limitation of highly selective controlled clinical trials is their applicability in the real world. Strict inclusion criteria, tailored management, and very close follow-up results in a bias that precludes universal implementation. An opportunity is the implementation of pragmatic clinical trials including registry-based randomized clinical trials. ⁴⁷⁷ These trials are less selective and less expensive alternatives to classical ones, especially for therapies used in clinical practice.

12. Key messages

1. Epidemiology of STEMI: Although the rate of mortality associated with ischaemic heart disease have reduced in Europe over the last few decades, this is still the single most common cause of death worldwide. The relative incidences of STEMI and NSTEMI are decreasing and increasing, respectively. Despite the decline in acute and long-term death associated with STEMI, in parallel with the widespread use of reperfusion, mortality remains substantial. The in-hospital mortality rates of unselected patients with STEMI in national European registries vary between 4–12%.

2. Gender aspects: Women tend to receive reperfusion therapy and other evidence-based treatments less frequently and/or in a delayed way than men. It is important to highlight that women and men receive equal benefit from a reperfusion and other STEMI-related therapies, and so both genders must be managed equally.

3. ECG and STEMI diagnosis: In some cases, patients may have coronary artery occlusion/global ischaemia in the absence of characteristic ST elevation (e.g. bundle branch block, ventricular pacing, hyperacute T-waves, isolated ST-depression in anterior leads, and/or universal ST depression with ST-elevation in aVR). In patients with the mentioned ECG changes and clinical presentation compatible with ongoing myocardial ischaemia, a primary PCI strategy (i.e. urgent angiography and PCI if indicated) should be followed.

4. Reperfusion strategy selection: STEMI diagnosis (defined as the time at which the ECG of a patient with ischaemic symptoms is interpreted as presenting ST-segment elevation or equivalent) is the time zero in the reperfusion strategy clock. STEMI patients should undergo a primary PCI strategy unless the anticipated absolute time from STEMI diagnosis to PCI-mediated reperfusion is > 120 min, when fibrinolysis should be initiated immediately (i.e. within 10 min of STEMI diagnosis).

5. STEMI management networks: Coordination between EMS and hospitals with common written protocols is at the centre of STEMI management. EMS should transfer patients to 24/7 high-volume PCI centres irrespective of whether the primary treatment strategy is PCI or pre-hospital fibrinolysis. EMS should always alert the PCI centre immediately after selection of the reperfusion strategy. Patient transfer to the PCI centre should bypass the emergency department.

6. Cardiac arrest and reperfusion strategy: Patients with ST-elevation on post-resuscitation ECG should undergo a primary PCI strategy. In cases without ST-segment elevation on post-resuscitation ECG but with a high suspicion of ongoing myocardial ischaemia, urgent angiography should be done within 2 h after a quick evaluation to exclude non-coronary causes. In all cases, the decision to perform urgent coronary angiography should take into account factors associated with poor neurological outcome.

7. Technical aspects during primary PCI: Routine radial access and routine DES implant is the standard of care during primary PCI. Routine thrombus aspiration or deferred stenting are contraindicated.

8. Management of non-IRA lesions: Treatment of severe stenosis (evaluated either by angiography or FFR) should be considered before hospital discharge (either immediately during the index PCI or staged at a later time). In cardiogenic shock, non-IRA PCI should be considered during the index procedure.

9. Antithrombotic therapy: Anticoagulants and DAPT are the cornerstone of the pharmacological approach in the acute phase of STEMI. Primary PCI: unfractionated heparin (enoxaparin and bivalirudin may be alternative), and loading dose of aspirin and prasugrel/ticagrelor. Fibrinolysis: enoxaparin (unfractionated heparin may be alternative), and loading dose of aspirin and clopidogrel. Maintenance therapy in the majority of patients is based on one year DAPT in the form of aspirin plus prasugrel/ticagrelor.

10. Early care: After reperfusion therapy, patients should be monitored for at least 24 h. Early ambulation and early discharge are the best option in uncomplicated patients. Consequently, time for implementing secondary prevention is limited highlighting the importance of close collaboration between all stakeholders.

11. Special patient subsets: Patients taking oral anticoagulants with renal insufficiency and/or the elderly represent a challenge in terms of optimal antithrombotic therapy. Special attention should be paid to dose adjustment of some pharmacological strategies in these subsets. Patients with diabetes and those not undergoing reperfusion represent another subset of patients that require additional attention.

12. Imaging in STEMI: Non-invasive imaging is very important for the acute and long-term management of STEMI patients.

13. MINOCA: A sizeable proportion of STEMI patients do not present significant coronary artery stenosis on urgent angiography. It is important to perform additional diagnostic tests in these patients to identify the aetiology and tailor appropriate therapy, which may be different from typical STEMI.

14. Quality indicators: In some cases, there is a gap between optimal guideline-based treatment and actual care of STEMI patients. In order to reduce this gap, it is important to measure established quality indicators to audit practice and improve outcomes in real-life. The use of well-defined and validated quality indicators to measure and improve STEMI care is recommended.

13. Evidenced-based 'to do and not to do' messages from the Guidelines

Recommendations with a class I or III and a level of evidence A or B. See 'Abbreviations and acronyms' list for explanation of abbreviations.

a

Class of recommendation.

b

Level of evidence.

Recommendations with a class I or III and a level of evidence A or B. See 'Abbreviations and acronyms' list for explanation of abbreviations.

a

Class of recommendation.

b

Level of evidence.

14. Web addenda

All Web figures and Web tables are available in the online Web Addenda at: European Heart Journal online and also via the ESC Website at: https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Acute-Myocardial-Infarction-in-patients-presenting-with-ST-segment-elevation-Ma

15. Appendix

ESC Committee for Practice Guidelines (CPG): Stephan Windecker (Chairperson) (Switzerland), Victor Aboyans (France), Stefan Agewall (Norway), Emanuele Barbato (Italy), Héctor Bueno (Spain), Antonio Coca (Spain), Jean-Philippe Collet (France), Ioan Mircea Coman (Romania), Veronica Dean (France), Victoria Delgado (The Netherlands), Donna Fitzsimons (UK), Oliver Gaemperli (Switzerland), Gerhard Hindricks (Germany), Bernard Iung (France), Peter Jüni (Canada), Hugo A. Katus (Germany), Juhani Knuuti (Finland), Patrizio Lancellotti (Belgium), Christophe Leclercq (France), Theresa McDonagh (UK), Massimo Francesco Piepoli (Italy), Piotr Ponikowski (Poland), Dimitrios J. Richter (Greece), Marco Roffi (Switzerland), Evgeny Shlyakhto (Russia), Iain A. Simpson (UK), Jose Luis Zamorano (Spain).

ESC National Cardiac Societies actively involved in the review process of the 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation:

Algeria: Algerian Society of Cardiology, Mohamed Chettibi; Armenia: Armenian Cardiologists Association, Hamlet G. Hayrapetyan; Austria: Austrian Society of Cardiology, Bernhard Metzler; Azerbaijan: Azerbaijan Society of Cardiology, Firdovsi Ibrahimov; Belarus: Belorussian Scientific Society of Cardiologists, Volha Sujayeva; Belgium: Belgian Society of Cardiology, Christophe Beauloye; Bosnia and Herzegovina: Association of Cardiologists of Bosnia and Herzegovina, Larisa Dizdarevic-Hudic; Bulgaria: Bulgarian Society of Cardiology, Kiril Karamfiloff; Croatia: Croatian Cardiac Society, Bosko Skoric; Cyprus: Cyprus Society of Cardiology, Loizos Antoniades; Czech Republic: Czech Society of Cardiology, Petr Tousek; Denmark: Danish Society of Cardiology, Christian Juhl Terkelsen; Egypt: Egyptian Society of Cardiology, Sameh Mohamad Shaheen; Estonia: Estonian Society of Cardiology, Toomas Marandi; Finland: Finnish Cardiac Society, Matti Niemelä; The Former Yugoslav Republic of Macedonia: Macedonian Society of Cardiology, Sasko Kedev; France: French Society of Cardiology, Martine Gilard; Georgia: Georgian Society of Cardiology, Alexander Aladashvili; Germany: German Cardiac Society, Albrecht Elsaesser; Greece: Hellenic Society of Cardiology, Ioannis Georgios Kanakakis; Hungary: Hungarian Society of Cardiology, Béla Merkely; Iceland: Icelandic Society of Cardiology, Thorarinn Gudnason; Israel: Israel Heart Society, Zaza Iakobishvili; Italy: Italian Federation of Cardiology, Leonardo Bolognese; Kazakhstan: Association of Cardiologists of Kazakhstan, Salim Berkinbayev; Kosovo: Kosovo Society of Cardiology, Gani Bajraktari; Kyrgyzstan: Kyrgyz Society of Cardiology, Medet Beishenkulov; Latvia: Latvian Society of Cardiology, Ilja Zake; Libya: Libyan Cardiac Society, Hisham Ben Lamin; Lithuania: Lithuanian Society of Cardiology, Olivija Gustiene; Luxembourg: Luxembourg Society of Cardiology, Bruno Pereira; Malta: Maltese Cardiac Society, Robert G. Xuereb; Morocco: Moroccan Society of Cardiology, Samir Ztot; Norway: Norwegian Society of Cardiology, Vibeke Juliebø; Poland: Polish Cardiac Society, Jacek Legutko; Portugal: Portuguese Society of Cardiology, Ana Teresa Timóteo; Romania: Romanian Society of Cardiology, Gabriel Tatu-Chiţoiu; Russian Federation: Russian Society of Cardiology, Alexey Yakovlev; San Marino: San Marino Society of Cardiology, Luca Bertelli; Serbia: Cardiology Society of Serbia, Milan Nedeljkovic; Slovakia: Slovak Society of Cardiology, Martin Studenčan; Slovenia: Slovenian Society of Cardiology, Matjaz Bunc; Spain: Spanish Society of Cardiology, Ana Maria García de Castro; Sweden: Swedish Society of Cardiology, Petur Petursson; Switzerland: Swiss Society of Cardiology, Raban Jeger; Tunisia: Tunisian Society of Cardiology and Cardio-Vascular Surgery, Mohamed Sami Mourali; Turkey: Turkish Society of Cardiology, Aylin Yildirir; Ukraine: Ukrainian Association of Cardiology, Alexander Parkhomenko; United Kingdom: British Cardiovascular Society, Chris P. Gale.

16. References

1

Windecker

S

,

Kolh

P

,

Alfonso

F

,

Collet

JP

,

Cremer

J

,

Falk

V

,

Filippatos

G

,

Hamm

C

,

Head

SJ

,

Juni

P

,

Kappetein

AP

,

Kastrati

A

,

Knuuti

J

,

Landmesser

U

,

Laufer

G

,

Neumann

FJ

,

Richter

DJ

,

Schauerte

P

,

Sousa Uva

M

,

Stefanini

GG

,

Taggart

DP

,

Torracca

L

,

Valgimigli

M

,

Wijns

W

,

Witkowski

A.

2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

.

Eur Heart J

2014

;

35

(

37

):

2541

–

2619

.

2

Roffi

M

,

Patrono

C

,

Collet

JP

,

Mueller

C

,

Valgimigli

M

,

Andreotti

F

,

Bax

JJ

,

Borger

MA

,

Brotons

C

,

Chew

DP

,

Gencer

B

,

Hasenfuss

G

,

Kjeldsen

K

,

Lancellotti

P

,

Landmesser

U

,

Mehilli

J

,

Mukherjee

D

,

Storey

RF

,

Windecker

S

,

Baumgartner

H

,

Gaemperli

O

,

Achenbach

S

,

Agewall

S

,

Badimon

L

,

Baigent

C

,

Bueno

H

,

Bugiardini

R

,

Carerj

S

,

Casselman

F

,

Cuisset

T

,

Erol

C

,

Fitzsimons

D

,

Halle

M

,

Hamm

C

,

Hildick-Smith

D

,

Huber

K

,

Iliodromitis

E

,

James

S

,

Lewis

BS

,

Lip

GY

,

Piepoli

MF

,

Richter

D

,

Rosemann

T

,

Sechtem

U

,

Steg

PG

,

Vrints

C

,

Luis Zamorano

J.

2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)

.

Eur Heart J

2016

;

37

(

3

):

267

–

315

.

3

Priori

SG

,

Blomstrom-Lundqvist

C

,

Mazzanti

A

,

Blom

N

,

Borggrefe

M

,

Camm

J

,

Elliott

PM

,

Fitzsimons

D

,

Hatala

R

,

Hindricks

G

,

Kirchhof

P

,

Kjeldsen

K

,

Kuck

KH

,

Hernandez-Madrid

A

,

Nikolaou

N

,

Norekval

TM

,

Spaulding

C

,

Van Veldhuisen

DJ.

2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC)

.

Eur Heart J

2015

;

36

(

41

):

2793

–

2867

.

4

Piepoli

MF

,

Hoes

AW

,

Agewall

S

,

Albus

C

,

Brotons

C

,

Catapano

AL

,

Cooney

MT

,

Corra

U

,

Cosyns

B

,

Deaton

C

,

Graham

I

,

Hall

MS

,

Hobbs

FD

,

Lochen

ML

,

Lollgen

H

,

Marques-Vidal

P

,

Perk

J

,

Prescott

E

,

Redon

J

,

Richter

DJ

,

Sattar

N

,

Smulders

Y

,

Tiberi

M

,

van der Worp

HB

,

van Dis

I

,

Verschuren

WM.

2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR)

.

Eur Heart J

2016

;

37

(

29

):

2315

–

2381

.

5

Kirchhof

P

,

Benussi

S

,

Kotecha

D

,

Ahlsson

A

,

Atar

D

,

Casadei

B

,

Castella

M

,

Diener

HC

,

Heidbuchel

H

,

Hendriks

J

,

Hindricks

G

,

Manolis

AS

,

Oldgren

J

,

Popescu

BA

,

Schotten

U

,

Van Putte

B

,

Vardas

P

,

Agewall

S

,

Camm

J

,

Baron Esquivias

G

,

Budts

W

,

Carerj

S

,

Casselman

F

,

Coca

A

,

De Caterina

R

,

Deftereos

S

,

Dobrev

D

,

Ferro

JM

,

Filippatos

G

,

Fitzsimons

D

,

Gorenek

B

,

Guenoun

M

,

Hohnloser

SH

,

Kolh

P

,

Lip

GY

,

Manolis

A

,

McMurray

J

,

Ponikowski

P

,

Rosenhek

R

,

Ruschitzka

F

,

Savelieva

I

,

Sharma

S

,

Suwalski

P

,

Tamargo

JL

,

Taylor

CJ

,

Van Gelder

IC

,

Voors

AA

,

Windecker

S

,

Zamorano

JL

,

Zeppenfeld

K.

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

.

Eur Heart J

2016

;

37

(

38

):

2893

–

2962

.

6

Ponikowski

P

,

Voors

AA

,

Anker

SD

,

Bueno

H

,

Cleland

JG

,

Coats

AJ

,

Falk

V

,

Gonzalez-Juanatey

JR

,

Harjola

VP

,

Jankowska

EA

,

Jessup

M

,

Linde

C

,

Nihoyannopoulos

P

,

Parissis

JT

,

Pieske

B

,

Riley

JP

,

Rosano

GM

,

Ruilope

LM

,

Ruschitzka

F

,

Rutten

FH

,

van der Meer

P.

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC

.

Eur Heart J

2016

;

37

(

27

):

2129

–

2200

.

7

Valgimigli

M

.

2017 ESC Focused Update on Dual Antiplatelet Therapy in Coronary Artery Disease in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). The Task Force for the Management of Dual Antiplatelet Therapy in Coronary Artery Disease of the European Society of Cardiology (ESC)

.

Eur Heart J

2017

.

8

Thygesen

K

,

Alpert

JS

,

Jaffe

AS

,

Simoons

ML

,

Chaitman

BR

,

White

HD

Writing Group on the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction

Thygesen

K

,

Alpert

JS

,

White

HD

,

Jaffe

AS

,

Katus

HA

,

Apple

FS

,

Lindahl

B

,

Morrow

DA

,

Chaitman

BA

,

Clemmensen

PM

,

Johanson

P

,

Hod

H

,

Underwood

R

,

Bax

JJ

,

Bonow

RO

,

Pinto

F

,

Gibbons

RJ

,

Fox

KA

,

Atar

D

,

Newby

LK

,

Galvani

M

,

Hamm

CW

,

Uretsky

BF

,

Steg

PG

,

Wijns

W

,

Bassand

JP

,

Menasche

P

,

Ravkilde

J

,

Ohman

EM

,

Antman

EM

,

Wallentin

LC

,

Armstrong

PW

,

Simoons

ML

,

Januzzi

JL

,

Nieminen

MS

,

Gheorghiade

M

,

Filippatos

G

,

Luepker

RV

,

Fortmann

SP

,

Rosamond

WD

,

Levy

D

,

Wood

D

,

Smith

SC

,

Hu

D

,

Lopez-Sendon

JL

,

Robertson

RM

,

Weaver

D

,

Tendera

M

,

Bove

AA

,

Parkhomenko

AN

,

Vasilieva

EJ

,

Mendis

S

,

ESC Committee for Practice Guidelines

.

Third universal definition of myocardial infarction

.

Eur Heart J

2012

;

33

(

20

):

2551

–

2567

.

9

Gehrie

ER

,

Reynolds

HR

,

Chen

AY

,

Neelon

BH

,

Roe

MT

,

Gibler

WB

,

Ohman

EM

,

Newby

LK

,

Peterson

ED

,

Hochman

JS.

Characterization and outcomes of women and men with non-ST-segment elevation myocardial infarction and nonobstructive coronary artery disease: results from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) quality improvement initiative

.

Am Heart J

2009

;

158

(

4

):

688

–

694

.

10

Pasupathy

S

,

Air

T

,

Dreyer

RP

,

Tavella

R

,

Beltrame

JF.

Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries

.

Circulation

2015

;

131

(

10

):

861

–

870

.

11

Niccoli

G

,

Scalone

G

,

Crea

F.

Acute myocardial infarction with no obstructive coronary atherosclerosis: mechanisms and management

.

Eur Heart J

2015

;

36

(

8

):

475

–

481

.

12

Agewall

S

,

Beltrame

JF

,

Reynolds

HR

,

Niessner

A

,

Rosano

G

,

Caforio

AL

,

De Caterina

R

,

Zimarino

M

,

Roffi

M

,

Kjeldsen

K

,

Atar

D

,

Kaski

JC

,

Sechtem

U

,

Tornvall

P

,

on behalf of the WG on Cardiovascular Pharmacotherapy

.

ESC working group position paper on myocardial infarction with non-obstructive coronary arteries

.

Eur Heart J

2017

;

38

(

3

):

143

–

153

.

13

Hartley

A

,

Marshall

DC

,

Salciccioli

JD

,

Sikkel

MB

,

Maruthappu

M

,

Shalhoub

J.

Trends in mortality from ischemic heart disease and cerebrovascular disease in Europe: 1980 to 2009

.

Circulation

2016

;

133

(

20

):

1916

–

1926

.

14

Townsend

N

,

Wilson

L

,

Bhatnagar

P

,

Wickramasinghe

K

,

Rayner

M

,

Nichols

M.

Cardiovascular disease in Europe: epidemiological update 2016

.

Eur Heart J

2016

;

37

(

42

):

3232

–

3245

.

15

Sugiyama

T

,

Hasegawa

K

,

Kobayashi

Y

,

Takahashi

O

,

Fukui

T

,

Tsugawa

Y.

Differential time trends of outcomes and costs of care for acute myocardial infarction hospitalizations by ST elevation and type of intervention in the United States, 2001-2011

.

J Am Heart Assoc

2015

;

4

(

3

):

e001445

.

16

McManus

DD

,

Gore

J

,

Yarzebski

J

,

Spencer

F

,

Lessard

D

,

Goldberg

RJ.

Recent trends in the incidence, treatment, and outcomes of patients with STEMI and NSTEMI

.

Am J Med

2011

;

124

(

1

):

40

–

47

.

17

Jernberg

T.

Swedeheart Annual Report 2015. In: Karolinska University Hospital, Huddinge, 14186 Stockholm;

2016

.

18

Widimsky

P

,

Wijns

W

,

Fajadet

J

,

de Belder

M

,

Knot

J

,

Aaberge

L

,

Andrikopoulos

G

,

Baz

JA

,

Betriu

A

,

Claeys

M

,

Danchin

N

,

Djambazov

S

,

Erne

P

,

Hartikainen

J

,

Huber

K

,

Kala

P

,

Klinceva

M

,

Kristensen

SD

,

Ludman

P

,

Ferre

JM

,

Merkely

B

,

Milicic

D

,

Morais

J

,

Noc

M

,

Opolski

G

,

Ostojic

M

,

Radovanovic

D

,

De Servi

S

,

Stenestrand

U

,

Studencan

M

,

Tubaro

M

,

Vasiljevic

Z

,

Weidinger

F

,

Witkowski

A

,

Zeymer

U

,

European Association for Percutaneous Cardiovascular Interventions

.

Reperfusion therapy for ST elevation acute myocardial infarction in Europe: description of the current situation in 30 countries

.

Eur Heart J

2010

;

31

(

8

):

943

–

957

.

19

Mozaffarian

D

,

Benjamin

EJ

,

Go

AS

,

Arnett

DK

,

Blaha

MJ

,

Cushman

M

,

de Ferranti

S

,

Despres

JP

,

Fullerton

HJ

,

Howard

VJ

,

Huffman

MD

,

Judd

SE

,

Kissela

BM

,

Lackland

DT

,

Lichtman

JH

,

Lisabeth

LD

,

Liu

S

,

Mackey

RH

,

Matchar

DB

,

McGuire

DK

,

Mohler

ER

3rd,

Moy

CS

,

Muntner

P

,

Mussolino

ME

,

Nasir

K

,

Neumar

RW

,

Nichol

G

,

Palaniappan

L

,

Pandey

DK

,

Reeves

MJ

,

Rodriguez

CJ

,

Sorlie

PD

,

Stein

J

,

Towfighi

A

,

Turan

TN

,

Virani

SS

,

Willey

JZ

,

Woo

D

,

Yeh

RW

,

Turner

MB

,

American Heart Association Statistics Committee and Stroke Statistics Subcommittee

.

Heart disease and stroke statistics—2015 update: a report from the American Heart Association

.

Circulation

2015

;

131

(

4

):

e29

–

322

.

20

Khera

S

,

Kolte

D

,

Gupta

T

,

Subramanian

KS

,

Khanna

N

,

Aronow

WS

,

Ahn

C

,

Timmermans

RJ

,

Cooper

HA

,

Fonarow

GC

,

Frishman

WH

,

Panza

JA

,

Bhatt

DL.

Temporal trends and sex differences in revascularization and outcomes of st-segment elevation myocardial infarction in younger adults in the United States

.

J Am Coll Cardiol

2015

;

66

(

18

):

1961

–

1972

.

21

Puymirat

E

,

Simon

T

,

Steg

PG

,

Schiele

F

,

Gueret

P

,

Blanchard

D

,

Khalife

K

,

Goldstein

P

,

Cattan

S

,

Vaur

L

,

Cambou

JP

,

Ferrieres

J

,

Danchin

N

,

USIK USIC 2000 Investigators

,

FAST MI Investigators

.

Association of changes in clinical characteristics and management with improvement in survival among patients with ST-elevation myocardial infarction

.

JAMA

2012

;

308

(

10

):

998

–

1006

.

22

Gale

CP

,

Allan

V

,

Cattle

BA

,

Hall

AS

,

West

RM

,

Timmis

A

,

Gray

HH

,

Deanfield

J

,

Fox

KA

,

Feltbower

R.

Trends in hospital treatments, including revascularisation, following acute myocardial infarction, 2003-2010: a multilevel and relative survival analysis for the National Institute for Cardiovascular Outcomes Research (NICOR)

.

Heart

2014

;

100

(

7

):

582

–

589

.

23

Kristensen

SD

,

Laut

KG

,

Fajadet

J

,

Kaifoszova

Z

,

Kala

P

,

Di Mario

C

,

Wijns

W

,

Clemmensen

P

,

Agladze

V

,

Antoniades

L

,

Alhabib

KF

,

De Boer

MJ

,

Claeys

MJ

,

Deleanu

D

,

Dudek

D

,

Erglis

A

,

Gilard

M

,

Goktekin

O

,

Guagliumi

G

,

Gudnason

T

,

Hansen

KW

,

Huber

K

,

James

S

,

Janota

T

,

Jennings

S

,

Kajander

O

,

Kanakakis

J

,

Karamfiloff

KK

,

Kedev

S

,

Kornowski

R

,

Ludman

PF

,

Merkely

B

,

Milicic

D

,

Najafov

R

,

Nicolini

FA

,

Noc

M

,

Ostojic

M

,

Pereira

H

,

Radovanovic

D

,

Sabate

M

,

Sobhy

M

,

Sokolov

M

,

Studencan

M

,

Terzic

I

,

Wahler

S

,

Widimsky

P

,

European Association for Percutaneous Cardiovascular Interventions

.

Reperfusion therapy for ST elevation acute myocardial infarction 2010/2011: current status in 37 ESC countries

.

Eur Heart J

2014

;

35

(

29

):

1957

–

1970

.

24

Pedersen

F

,

Butrymovich

V

,

Kelbaek

H

,

Wachtell

K

,

Helqvist

S

,

Kastrup

J

,

Holmvang

L

,

Clemmensen

P

,

Engstrom

T

,

Grande

P

,

Saunamaki

K

,

Jorgensen

E.

Short- and long-term cause of death in patients treated with primary PCI for STEMI

.

J Am Coll Cardiol

2014

;

64

(

20

):

2101

–

2108

.

25

Fokkema

ML

,

James

SK

,

Albertsson

P

,

Akerblom

A

,

Calais

F

,

Eriksson

P

,

Jensen

J

,

Nilsson

T

,

de Smet

BJ

,

Sjogren

I

,

Thorvinger

B

,

Lagerqvist

B.

Population trends in percutaneous coronary intervention: 20-year results from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry)

.

J Am Coll Cardiol

2013

;

61

(

12

):

1222

–

1230

.

26

EUGenMed Cardiovascular Clinical Study Group

,

Regitz-Zagrosek

V

,

Oertelt-Prigione

S

,

Prescott

E

,

Franconi

F

,

Gerdts

E

,

Foryst-Ludwig

A

,

Maas

AH

,

Kautzky-Willer

A

,

Knappe-Wegner

D

,

Kintscher

U

,

Ladwig

KH

,

Schenck-Gustafsson

K

,

Stangl

V.

Gender in cardiovascular diseases: impact on clinical manifestations, management, and outcomes

.

Eur Heart J

2016

;

37

(

1

):

24

–

34

.

27

Brieger

D

,

Eagle

KA

,

Goodman

SG

,

Steg

PG

,

Budaj

A

,

White

K

,

Montalescot

G.

Acute coronary syndromes without chest pain, an underdiagnosed and undertreated high-risk group: insights from the Global Registry of Acute Coronary Events

.

Chest

2004

;

126

(

2

):

461

–

469

.

28

Kaul

P

,

Armstrong

PW

,

Sookram

S

,

Leung

BK

,

Brass

N

,

Welsh

RC.

Temporal trends in patient and treatment delay among men and women presenting with ST-elevation myocardial infarction

.

Am Heart J

2011

;

161

(

1

):

91

–

97

.

29

Diercks

DB

,

Owen

KP

,

Kontos

MC

,

Blomkalns

A

,

Chen

AY

,

Miller

C

,

Wiviott

S

,

Peterson

ED.

Gender differences in time to presentation for myocardial infarction before and after a national women's cardiovascular awareness campaign: a temporal analysis from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation (CRUSADE) and the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network-Get with the Guidelines (NCDR ACTION Registry-GWTG)

.

Am Heart J

2010

;

160

(

1

):

80

–

87.e3

.

30

Kang

SH

,

Suh

JW

,

Yoon

CH

,

Cho

MC

,

Kim

YJ

,

Chae

SC

,

Yoon

JH

,

Gwon

HC

,

Han

KR

,

Kim

JH

,

Ahn

YK

,

Jeong

MH

,

Kim

HS

,

Choi

DJ

,

KAMIR/KorMI Registry

.

Sex differences in management and mortality of patients with ST-elevation myocardial infarction (from the Korean Acute Myocardial Infarction National Registry)

.

Am J Cardiol

2012

;

109

(

6

):

787

–

793

.

31

Kyto

V

,

Sipila

J

,

Rautava

P.

Gender and in-hospital mortality of ST-segment elevation myocardial infarction (from a multihospital nationwide registry study of 31,689 patients)

.

Am J Cardiol

2015

;

115

(

3

):

303

–

306

.

32

Hvelplund

A

,

Galatius

S

,

Madsen

M

,

Rasmussen

JN

,

Rasmussen

S

,

Madsen

JK

,

Sand

NP

,

Tilsted

HH

,

Thayssen

P

,

Sindby

E

,

Hojbjerg

S

,

Abildstrom

SZ.

Women with acute coronary syndrome are less invasively examined and subsequently less treated than men

.

Eur Heart J

2010

;

31

(

6

):

684

–

690

.

33

Nguyen

JT

,

Berger

AK

,

Duval

S

,

Luepker

RV.

Gender disparity in cardiac procedures and medication use for acute myocardial infarction

.

Am Heart J

2008

;

155

(

5

):

862

–

868

.

34

de Torbal

A

,

Boersma

E

,

Kors

JA

,

van Herpen

G

,

Deckers

JW

,

van der Kuip

DA

,

Stricker

BH

,

Hofman

A

,

Witteman

JC.

Incidence of recognized and unrecognized myocardial infarction in men and women aged 55 and older: the Rotterdam Study

.

Eur Heart J

2006

;

27

(

6

):

729

–

736

.

35

Henrikson

CA

,

Howell

EE

,

Bush

DE

,

Miles

JS

,

Meininger

GR

,

Friedlander

T

,

Bushnell

AC

,

Chandra-Strobos

N.

Chest pain relief by nitroglycerin does not predict active coronary artery disease

.

Ann Intern Med

2003

;

139

(

12

):

979

–

986

.

36

Diercks

DB

,

Peacock

WF

,

Hiestand

BC

,

Chen

AY

,

Pollack

CV

Jr,

Kirk

JD

,

Smith

SC

Jr,

Gibler

WB

,

Ohman

EM

,

Blomkalns

AL

,

Newby

LK

,

Hochman

JS

,

Peterson

ED

,

Roe

MT.

Frequency and consequences of recording an electrocardiogram >10 minutes after arrival in an emergency room in non-ST-segment elevation acute coronary syndromes (from the CRUSADE Initiative)

.

Am J Cardiol

2006

;

97

(

4

):

437

–

442

.

37

Tubaro

M

,

Danchin

N

,

Goldstein

P

,

Filippatos

G

,

Hasin

Y

,

Heras

M

,

Jansky

P

,

Norekval

TM

,

Swahn

E

,

Thygesen

K

,

Vrints

C

,

Zahger

D

,

Arntz

HR

,

Bellou

A

,

De La Coussaye

JE

,

De Luca

L

,

Huber

K

,

Lambert

Y

,

Lettino

M

,

Lindahl

B

,

McLean

S

,

Nibbe

L

,

Peacock

WF

,

Price

S

,

Quinn

T

,

Spaulding

C

,

Tatu-Chitoiu

G

,

Van De Werf

F.

Pre-hospital treatment of STEMI patients. A scientific statement of the Working Group Acute Cardiac Care of the European Society of Cardiology

.

Acute Card Care

2011

;

13

(

2

):

56

–

67

.

38

Rokos

IC

,

French

WJ

,

Koenig

WJ

,

Stratton

SJ

,

Nighswonger

B

,

Strunk

B

,

Jewell

J

,

Mahmud

E

,

Dunford

JV

,

Hokanson

J

,

Smith

SW

,

Baran

KW

,

Swor

R

,

Berman

A

,

Wilson

BH

,

Aluko

AO

,

Gross

BW

,

Rostykus

PS

,

Salvucci

A

,

Dev

V

,

McNally

B

,

Manoukian

SV

,

King

SB

3rd.

Integration of pre-hospital electrocardiograms and ST-elevation myocardial infarction receiving center (SRC) networks: impact on door-to-balloon times across 10 independent regions

.

JACC Cardiovasc Interv

2009

;

2

(

4

):

339

–

346

.

39

Quinn

T

,

Johnsen

S

,

Gale

CP

,

Snooks

H

,

McLean

S

,

Woollard

M

,

Weston

C.

Effects of prehospital 12-lead ECG on processes of care and mortality in acute coronary syndrome: a linked cohort study from the Myocardial Ischaemia National Audit Project

.

Heart

2014

;

100

(

12

):

944

–

950

.

40

Sorensen

JT

,

Terkelsen

CJ

,

Norgaard

BL

,

Trautner

S

,

Hansen

TM

,

Botker

HE

,

Lassen

JF

,

Andersen

HR.

Urban and rural implementation of pre-hospital diagnosis and direct referral for primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction

.

Eur Heart J

2011

;

32

(

4

):

430

–

436

.

41

Chan

AW

,

Kornder

J

,

Elliott

H

,

Brown

RI

,

Dorval

JF

,

Charania

J

,

Zhang

R

,

Ding

L

,

Lalani

A

,

Kuritzky

RA

,

Simkus

GJ.

Improved survival associated with pre-hospital triage strategy in a large regional ST-segment elevation myocardial infarction program

.

JACC Cardiovasc Interv

2012

;

5

(

12

):

1239

–

46

.

42

Dhruva

VN

,

Abdelhadi

SI

,

Anis

A

,

Gluckman

W

,

Hom

D

,

Dougan

W

,

Kaluski

E

,

Haider

B

,

Klapholz

M.

ST-Segment Analysis Using Wireless Technology in Acute Myocardial Infarction (STAT-MI) trial

.

J Am Coll Cardiol

2007

;

50

(

6

):

509

–

513

.

43

Lopez-Sendon

J

,

Coma-Canella

I

,

Alcasena

S

,

Seoane

J

,

Gamallo

C.

Electrocardiographic findings in acute right ventricular infarction: sensitivity and specificity of electrocardiographic alterations in right precordial leads V4R, V3R, V1, V2, and V3

.

J Am Coll Cardiol

1985

;

6

(

6

):

1273

–

1279

.

44

O'Doherty

M

,

Tayler

DI

,

Quinn

E

,

Vincent

R

,

Chamberlain

DA.

Five hundred patients with myocardial infarction monitored within one hour of symptoms

.

BMJ (Clin Res Ed)

1983

;

286

(

6375

):

1405

–

1408

.

45

Mehta

RH

,

Starr

AZ

,

Lopes

RD

,

Hochman

JS

,

Widimsky

P

,

Pieper

KS

,

Armstrong

PW

,

Granger

CB.

Incidence of and outcomes associated with ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention

.

JAMA

2009

;

301

(

17

):

1779

–

1789

.

46

Rokos

IC

,

Farkouh

ME

,

Reiffel

J

,

Dressler

O

,

Mehran

R

,

Stone

GW.

Correlation between index electrocardiographic patterns and pre-intervention angiographic findings: insights from the HORIZONS-AMI trial

.

Catheter Cardiovasc Interv

2012

;

79

(

7

):

1092

–

1098

.

47

Stribling

WK

,

Kontos

MC

,

Abbate

A

,

Cooke

R

,

Vetrovec

GW

,

Dai

D

,

Honeycutt

E

,

Wang

TY

,

Lotun

K.

Left circumflex occlusion in acute myocardial infarction (from the National Cardiovascular Data Registry)

.

Am J Cardiol

2011

;

108

(

7

):

959

–

963

.

48

Dixon

WC

4th,

Wang

TY

,

Dai

D

,

Shunk

KA

,

Peterson

ED

,

Roe

MT.

Anatomic distribution of the culprit lesion in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: findings from the National Cardiovascular Data Registry

.

J Am Coll Cardiol

2008

;

52

(

16

):

1347

–

1348

.

49

Wang

TY

,

Zhang

M

,

Fu

Y

,

Armstrong

PW

,

Newby

LK

,

Gibson

CM

,

Moliterno

DJ

,

Van de Werf

F

,

White

HD

,

Harrington

RA

,

Roe

MT.

Incidence, distribution, and prognostic impact of occluded culprit arteries among patients with non-ST-elevation acute coronary syndromes undergoing diagnostic angiography

.

Am Heart J

2009

;

157

(

4

):

716

–

723

.

50

Sgarbossa

EB

,

Pinski

SL

,

Barbagelata

A

,

Underwood

DA

,

Gates

KB

,

Topol

EJ

,

Califf

RM

,

Wagner

GS.

Electrocardiographic diagnosis of evolving acute myocardial infarction in the presence of left bundle-branch block. GUSTO-1 (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) Investigators

.

N Engl J Med

1996

;

334

(

8

):

481

–

487

.

51

Wong

CK

,

French

JK

,

Aylward

PE

,

Stewart

RA

,

Gao

W

,

Armstrong

PW

,

Van De Werf

FJ

,

Simes

RJ

,

Raffel

OC

,

Granger

CB

,

Califf

RM

,

White

HD.

Patients with prolonged ischemic chest pain and presumed-new left bundle branch block have heterogeneous outcomes depending on the presence of ST-segment changes

.

J Am Coll Cardiol

2005

;

46

(

1

):

29

–

38

.

52

Shlipak

MG

,

Lyons

WL

,

Go

AS

,

Chou

TM

,

Evans

GT

,

Browner

WS.

Should the electrocardiogram be used to guide therapy for patients with left bundle-branch block and suspected myocardial infarction?

JAMA

1999

;

281

(

8

):

714

–

719

.

53

Lopes

RD

,

Siha

H

,

Fu

Y

,

Mehta

RH

,

Patel

MR

,

Armstrong

PW

,

Granger

CB.

Diagnosing acute myocardial infarction in patients with left bundle branch block

.

Am J Cardiol

2011

;

108

(

6

):

782

–

788

.

54

Chang

AM

,

Shofer

FS

,

Tabas

JA

,

Magid

DJ

,

McCusker

CM

,

Hollander

JE.

Lack of association between left bundle-branch block and acute myocardial infarction in symptomatic ED patients

.

Am J Emerg Med

2009

;

27

(

8

):

916

–

921

.

55

Widimsky

P

,

Rohac

F

,

Stasek

J

,

Kala

P

,

Rokyta

R

,

Kuzmanov

B

,

Jakl

M

,

Poloczek

M

,

Kanovsky

J

,

Bernat

I

,

Hlinomaz

O

,

Belohlavek

J

,

Kral

A

,

Mrazek

V

,

Grigorov

V

,

Djambazov

S

,

Petr

R

,

Knot

J

,

Bilkova

D

,

Fischerova

M

,

Vondrak

K

,

Maly

M

,

Lorencova

A.

Primary angioplasty in acute myocardial infarction with right bundle branch block: should new onset right bundle branch block be added to future guidelines as an indication for reperfusion therapy?

Eur Heart J

2012

;

33

(

1

):

86

–

95

.

56

Madias

JE.

The nonspecificity of ST-segment elevation > or = 5.0 mm in V1-V3 in the diagnosis of acute myocardial infarction in the presence of ventricular paced rhythm

.

J Electrocardiol

2004

;

37

(

2

):

135

–

139

.

57

Sgarbossa

EB

,

Pinski

SL

,

Gates

KB

,

Wagner

GS.

Early electrocardiographic diagnosis of acute myocardial infarction in the presence of ventricular paced rhythm. GUSTO-I Investigators

.

Am J Cardiol

1996

;

77

(

5

):

423

–

424

.

58

Krishnaswamy

A

,

Lincoff

AM

,

Menon

V.

Magnitude and consequences of missing the acute infarct-related circumflex artery

.

Am Heart J

2009

;

158

(

5

):

706

–

712

.

59

From

AM

,

Best

PJ

,

Lennon

RJ

,

Rihal

CS

,

Prasad

A.

Acute myocardial infarction due to left circumflex artery occlusion and significance of ST-segment elevation

.

Am J Cardiol

2010

;

106

(

8

):

1081

–

1085

.

60

Yan

AT

,

Yan

RT

,

Kennelly

BM

,

Anderson

FA

Jr,

Budaj

A

,

Lopez-Sendon

J

,

Brieger

D

,

Allegrone

J

,

Steg

G

,

Goodman

SG.

Relationship of ST elevation in lead aVR with angiographic findings and outcome in non-ST elevation acute coronary syndromes

.

Am Heart J

2007

;

154

(

1

):

71

–

78

.

61

Hobl

EL

,

Stimpfl

T

,

Ebner

J

,

Schoergenhofer

C

,

Derhaschnig

U

,

Sunder-Plassmann

R

,

Jilma-Stohlawetz

P

,

Mannhalter

C

,

Posch

M

,

Jilma

B.

Morphine decreases clopidogrel concentrations and effects: a randomized, double-blind, placebo-controlled trial

.

J Am Coll Cardiol

2014

;

63

(

7

):

630

–

635

.

62

Parodi

G

,

Bellandi

B

,

Xanthopoulou

I

,

Capranzano

P

,

Capodanno

D

,

Valenti

R

,

Stavrou

K

,

Migliorini

A

,

Antoniucci

D

,

Tamburino

C

,

Alexopoulos

D.

Morphine is associated with a delayed activity of oral antiplatelet agents in patients with ST-elevation acute myocardial infarction undergoing primary percutaneous coronary intervention

.

Circ Cardiovasc Interv

2015

;

8

(

1

):

e001593

.

63

Kubica

J

,

Adamski

P

,

Ostrowska

M

,

Sikora

J

,

Kubica

JM

,

Sroka

WD

,

Stankowska

K

,

Buszko

K

,

Navarese

EP

,

Jilma

B

,

Siller-Matula

JM

,

Marszall

MP

,

Rosc

D

,

Kozinski

M.

Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial

.

Eur Heart J

2016

;

37

(

3

):

245

–

252

.

64

Stub

D

,

Smith

K

,

Bernard

S

,

Nehme

Z

,

Stephenson

M

,

Bray

JE

,

Cameron

P

,

Barger

B

,

Ellims

AH

,

Taylor

AJ

,

Meredith

IT

,

Kaye

DM.

Air versus oxygen in ST-segment-elevation myocardial infarction

.

Circulation

2015

;

131

(

24

):

2143

–

2150

.

65

Cabello

JB

,

Burls

A

,

Emparanza

JI

,

Bayliss

S

,

Quinn

T.

Oxygen therapy for acute myocardial infarction

.

Cochrane Database Syst Rev

2013

;

8

:

CD007160

.

66

Hofmann

R

,

James

SK

,

Svensson

L

,

Witt

N

,

Frick

M

,

Lindahl

B

,

Ostlund

O

,

Ekelund

U

,

Erlinge

D

,

Herlitz

J

,

Jernberg

T.

Determination of the role of oxygen in suspected acute myocardial infarction trial

.

Am Heart J

2014

;

167

(

3

):

322

–

328

.

67

Rawles

JM

,

Kenmure

AC.

Controlled trial of oxygen in uncomplicated myocardial infarction

.

BMJ

1976

;

1

(

6018

):

1121

–

1123

.

68

Larsen

JM

,

Ravkilde

J.

Acute coronary angiography in patients resuscitated from out-of-hospital cardiac arrest: a systematic review and meta-analysis

.

Resuscitation

2012

;

83

(

12

):

1427

–

1433

.

69

Garot

P

,

Lefevre

T

,

Eltchaninoff

H

,

Morice

MC

,

Tamion

F

,

Abry

B

,

Lesault

PF

,

Le Tarnec

JY

,

Pouges

C

,

Margenet

A

,

Monchi

M

,

Laurent

I

,

Dumas

P

,

Garot

J

,

Louvard

Y.

Six-month outcome of emergency percutaneous coronary intervention in resuscitated patients after cardiac arrest complicating ST-elevation myocardial infarction

.

Circulation

2007

;

115

(

11

):

1354

–

1362

.

70

Kern

KB

,

Rahman

O.

Emergent percutaneous coronary intervention for resuscitated victims of out-of-hospital cardiac arrest

.

Catheter Cardiovasc Interv

2010

;

75

(

4

):

616

–

624

.

71

Spaulding

CM

,

Joly

LM

,

Rosenberg

A

,

Monchi

M

,

Weber

SN

,

Dhainaut

JF

,

Carli

P.

Immediate coronary angiography in survivors of out-of-hospital cardiac arrest

.

N Engl J Med

1997

;

336

(

23

):

1629

–

1633

.

72

Dumas

F

,

Cariou

A

,

Manzo-Silberman

S

,

Grimaldi

D

,

Vivien

B

,

Rosencher

J

,

Empana

JP

,

Carli

P

,

Mira

JP

,

Jouven

X

,

Spaulding

C.

Immediate percutaneous coronary intervention is associated with better survival after out-of-hospital cardiac arrest: insights from the PROCAT (Parisian Region Out of hospital Cardiac ArresT) registry

.

Circ Cardiovasc Interv

2010

;

3

(

3

):

200

–

207

.

73

Noc

M

,

Fajadet

J

,

Lassen

JF

,

Kala

P

,

MacCarthy

P

,

Olivecrona

GK

,

Windecker

S

,

Spaulding

C

,

European Association for Percutaneous Cardiovascular Interventions

,

Stent for Life Group

.

Invasive coronary treatment strategies for out-of-hospital cardiac arrest: a consensus statement from the European Association for Percutaneous Cardiovascular Interventions (EAPCI)/Stent for LIfe (SFL) groups

.

EuroIntervention

2014

;

10

(

1

):

31

–

37

.

74

Monsieurs

KG

,

Nolan

JP

,

Bossaert

LL

,

Greif

R

,

Maconochie

IK

,

Nikolaou

NI

,

Perkins

GD

,

Soar

J

,

Truhlar

A

,

Wyllie

J

,

Zideman

DA.

European Resuscitation Council Guidelines for Resuscitation 2015: Section 1. Executive summary

.

Resuscitation

2015

;

95

:

1

–

80

.

75

Reynolds

JC

,

Frisch

A

,

Rittenberger

JC

,

Callaway

CW.

Duration of resuscitation efforts and functional outcome after out-of-hospital cardiac arrest: when should we change to novel therapies?

Circulation

2013

;

128

(

23

):

2488

–

2494

.

76

Moulaert

VR

,

Verbunt

JA

,

van Heugten

CM

,

Wade

DT.

Cognitive impairments in survivors of out-of-hospital cardiac arrest: a systematic review

.

Resuscitation

2009

;

80

(

3

):

297

–

305

.

77

Hypothermia after Cardiac Arrest Study Group

.

Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest

.

N Engl J Med

2002

;

346

(

8

):

549

–

556

.

78

Bernard

SA

,

Gray

TW

,

Buist

MD

,

Jones

BM

,

Silvester

W

,

Gutteridge

G

,

Smith

K.

Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia

.

N Engl J Med

2002

;

346

(

8

):

557

–

563

.

79

Nikolaou

NI

,

Welsford

M

,

Beygui

F

,

Bossaert

L

,

Ghaemmaghami

C

,

Nonogi

H

,

O'Connor

RE

,

Pichel

DR

,

Scott

T

,

Walters

DL

,

Woolfrey

KG.

Part 5: Acute coronary syndromes: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations

.

Resuscitation

2015

;

95

:

e121

–

e146

.

80

Belliard

G

,

Catez

E

,

Charron

C

,

Caille

V

,

Aegerter

P

,

Dubourg

O

,

Jardin

F

,

Vieillard-Baron

A.

Efficacy of therapeutic hypothermia after out-of-hospital cardiac arrest due to ventricular fibrillation

.

Resuscitation

2007

;

75

(

2

):

252

–

259

.

81

Nielsen

N

,

Wetterslev

J

,

Cronberg

T

,

Erlinge

D

,

Gasche

Y

,

Hassager

C

,

Horn

J

,

Hovdenes

J

,

Kjaergaard

J

,

Kuiper

M

,

Pellis

T

,

Stammet

P

,

Wanscher

M

,

Wise

MP

,

Aneman

A

,

Al-Subaie

N

,

Boesgaard

S

,

Bro-Jeppesen

J

,

Brunetti

I

,

Bugge

JF

,

Hingston

CD

,

Juffermans

NP

,

Koopmans

M

,

Kober

L

,

Langorgen

J

,

Lilja

G

,

Moller

JE

,

Rundgren

M

,

Rylander

C

,

Smid

O

,

Werer

C

,

Winkel

P

,

Friberg

H

,

TTM Trial Investigators

.

Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest

.

N Engl J Med

2013

;

369

(

23

):

2197

–

2206

.

82

Vaahersalo

J

,

Hiltunen

P

,

Tiainen

M

,

Oksanen

T

,

Kaukonen

KM

,

Kurola

J

,

Ruokonen

E

,

Tenhunen

J

,

Ala-Kokko

T

,

Lund

V

,

Reinikainen

M

,

Kiviniemi

O

,

Silfvast

T

,

Kuisma

M

,

Varpula

T

,

Pettila

V.

Therapeutic hypothermia after out-of-hospital cardiac arrest in Finnish intensive care units: the FINNRESUSCI study

.

Intensive Care Med

2013

;

39

(

5

):

826

–

837

.

83

Penela

D

,

Magaldi

M

,

Fontanals

J

,

Martin

V

,

Regueiro

A

,

Ortiz

JT

,

Bosch

X

,

Sabate

M

,

Heras

M.

Hypothermia in acute coronary syndrome: brain salvage versus stent thrombosis?

J Am Coll Cardiol

2013

;

61

(

6

):

686

–

687

.

84

Shah

N

,

Chaudhary

R

,

Mehta

K

,

Agarwal

V

,

Garg

J

,

Freudenberger

R

,

Jacobs

L

,

Cox

D

,

Kern

KB

,

Patel

N.

Therapeutic hypothermia and stent thrombosis: a nationwide analysis

.

JACC Cardiovasc Interv

2016

;

9

(

17

):

1801

–

1811

.

85

Garcia-Tejada

J

,

Jurado-Roman

A

,

Rodriguez

J

,

Velazquez

M

,

Hernandez

F

,

Albarran

A

,

Martin-Asenjo

R

,

Granda-Nistal

C

,

Coma

R

,

Tascon

J.

Post-resuscitation electrocardiograms, acute coronary findings and in-hospital prognosis of survivors of out-of-hospital cardiac arrest

.

Resuscitation

2014

;

85

(

9

):

1245

–

1250

.

86

Kim

F

,

Nichol

G

,

Maynard

C

,

Hallstrom

A

,

Kudenchuk

PJ

,

Rea

T

,

Copass

MK

,

Carlbom

D

,

Deem

S

,

Longstreth

WT

Jr,

Olsufka

M

,

Cobb

LA.

Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial

.

JAMA

2014

;

311

(

1

):

45

–

52

.

87

Terkelsen

CJ

,

Sorensen

JT

,

Maeng

M

,

Jensen

LO

,

Tilsted

HH

,

Trautner

S

,

Vach

W

,

Johnsen

SP

,

Thuesen

L

,

Lassen

JF.

System delay and mortality among patients with STEMI treated with primary percutaneous coronary intervention

.

JAMA

2010

;

304

(

7

):

763

–

771

.

88

Fordyce

CB

,

Al-Khalidi

HR

,

Jollis

JG

,

Roettig

ML

,

Gu

J

,

Bagai

A

,

Berger

PB

,

Corbett

CC

,

Dauerman

HL

,

Fox

K

,

Garvey

JL

,

Henry

TD

,

Rokos

IC

,

Sherwood

MW

,

Wilson

BH

,

Granger

CB

,

STEMI Systems Accelerator Project

.

Association of rapid care process implementation on reperfusion times across multiple ST-segment-elevation myocardial infarction networks

.

Circ Cardiovasc Interv

2017

;

10

(

1

):

e004061

.

89

Stowens

JC

,

Sonnad

SS

,

Rosenbaum

RA.

Using EMS dispatch to trigger STEMI alerts decreases door-to-balloon times

.

West J Emerg Med

2015

;

16

(

3

):

472

–

480

.

90

Squire

BT

,

Tamayo-Sarver

JH

,

Rashi

P

,

Koenig

W

,

Niemann

JT.

Effect of prehospital cardiac catheterization lab activation on door-to-balloon time, mortality, and false-positive activation

.

Prehosp Emerg Care

2014

;

18

(

1

):

1

–

8

.

91

Nallamothu

BK

,

Normand

SL

,

Wang

Y

,

Hofer

TP

,

Brush

JE

Jr,

Messenger

JC

,

Bradley

EH

,

Rumsfeld

JS

,

Krumholz

HM.

Relation between door-to-balloon times and mortality after primary percutaneous coronary intervention over time: a retrospective study

.

Lancet

2015

;

385

(

9973

):

1114

–

1122

.

92

Bagai

A

,

Jollis

JG

,

Dauerman

HL

,

Peng

SA

,

Rokos

IC

,

Bates

ER

,

French

WJ

,

Granger

CB

,

Roe

MT.

Emergency department bypass for ST-segment-elevation myocardial infarction patients identified with a prehospital electrocardiogram: a report from the American Heart Association Mission: Lifeline program

.

Circulation

2013

;

128

(

4

):

352

–

359

.

93

Wang

TY

,

Nallamothu

BK

,

Krumholz

HM

,

Li

S

,

Roe

MT

,

Jollis

JG

,

Jacobs

AK

,

Holmes

DR

,

Peterson

ED

,

Ting

HH.

Association of door-in to door-out time with reperfusion delays and outcomes among patients transferred for primary percutaneous coronary intervention

.

JAMA

2011

;

305

(

24

):

2540

–

2547

.

94

Huber

K

,

De Caterina

R

,

Kristensen

SD

,

Verheugt

FW

,

Montalescot

G

,

Maestro

LB

,

Van de Werf

F.

Pre-hospital reperfusion therapy: a strategy to improve therapeutic outcome in patients with ST-elevation myocardial infarction

.

Eur Heart J

2005

;

26

(

19

):

2063

–

2074

.

95

Welsh

RC

,

Chang

W

,

Goldstein

P

,

Adgey

J

,

Granger

CB

,

Verheugt

FW

,

Wallentin

L

,

Van de Werf

F

,

Armstrong

PW.

Time to treatment and the impact of a physician on prehospital management of acute ST elevation myocardial infarction: insights from the ASSENT-3 PLUS trial

.

Heart

2005

;

91

(

11

):

1400

–

1406

.

96

Bjorklund

E

,

Stenestrand

U

,

Lindback

J

,

Svensson

L

,

Wallentin

L

,

Lindahl

B.

Pre-hospital thrombolysis delivered by paramedics is associated with reduced time delay and mortality in ambulance-transported real-life patients with ST-elevation myocardial infarction

.

Eur Heart J

2006

;

27

(

10

):

1146

–

1152

.

97

Steg

PG

,

Bonnefoy

E

,

Chabaud

S

,

Lapostolle

F

,

Dubien

PY

,

Cristofini

P

,

Leizorovicz

A

,

Touboul

P

,

CAPTIM Investigators

.

Impact of time to treatment on mortality after prehospital fibrinolysis or primary angioplasty: data from the CAPTIM randomized clinical trial

.

Circulation

2003

;

108

(

23

):

2851

–

2856

.

98

Bonnefoy

E

,

Steg

PG

,

Boutitie

F

,

Dubien

PY

,

Lapostolle

F

,

Roncalli

J

,

Dissait

F

,

Vanzetto

G

,

Leizorowicz

A

,

Kirkorian

G

,

Mercier

C

,

McFadden

EP

,

Touboul

P.

Comparison of primary angioplasty and pre-hospital fibrinolysis in acute myocardial infarction (CAPTIM) trial: a 5-year follow-up

.

Eur Heart J

2009

;

30

(

13

):

1598

–

1606

.

99

Danchin

N

,

Coste

P

,

Ferrieres

J

,

Steg

PG

,

Cottin

Y

,

Blanchard

D

,

Belle

L

,

Ritz

B

,

Kirkorian

G

,

Angioi

M

,

Sans

P

,

Charbonnier

B

,

Eltchaninoff

H

,

Gueret

P

,

Khalife

K

,

Asseman

P

,

Puel

J

,

Goldstein

P

,

Cambou

JP

,

Simon

T

,

FAST-MI Investigators

.

Comparison of thrombolysis followed by broad use of percutaneous coronary intervention with primary percutaneous coronary intervention for ST-segment-elevation acute myocardial infarction: Data from the French registry on acute ST-elevation myocardial infarction (FAST-MI)

.

Circulation

2008

;

118

(

3

):

268

–

276

.

100

Kalla

K

,

Christ

G

,

Karnik

R

,

Malzer

R

,

Norman

G

,

Prachar

H

,

Schreiber

W

,

Unger

G

,

Glogar

HD

,

Kaff

A

,

Laggner

AN

,

Maurer

G

,

Mlczoch

J

,

Slany

J

,

Weber

HS

,

Huber

K.

Implementation of guidelines improves the standard of care: the Viennese registry on reperfusion strategies in ST-elevation myocardial infarction (Vienna STEMI registry)

.

Circulation

2006

;

113

(

20

):

2398

–

2405

.

101

Henry

TD

,

Sharkey

SW

,

Burke

MN

,

Chavez

IJ

,

Graham

KJ

,

Henry

CR

,

Lips

DL

,

Madison

JD

,

Menssen

KM

,

Mooney

MR

,

Newell

MC

,

Pedersen

WR

,

Poulose

AK

,

Traverse

JH

,

Unger

BT

,

Wang

YL

,

Larson

DM.

A regional system to provide timely access to percutaneous coronary intervention for ST-elevation myocardial infarction

.

Circulation

2007

;

116

(

7

):

721

–

728

.

102

Le May

MR

,

So

DY

,

Dionne

R

,

Glover

CA

,

Froeschl

MP

,

Wells

GA

,

Davies

RF

,

Sherrard

HL

,

Maloney

J

,

Marquis

JF

,

O'Brien

ER

,

Trickett

J

,

Poirier

P

,

Ryan

SC

,

Ha

A

,

Joseph

PG

,

Labinaz

M.

A citywide protocol for primary PCI in ST-segment elevation myocardial infarction

.

N Engl J Med

2008

;

358

(

3

):

231

–

240

.

103

Knot

J

,

Widimsky

P

,

Wijns

W

,

Stenestrand

U

,

Kristensen

SD

,

Van

THA

,

Weidinger

F

,

Janzon

M

,

Norgaard

BL

,

Soerensen

JT

,

van de Wetering

H

,

Thygesen

K

,

Bergsten

PA

,

Digerfeldt

C

,

Potgieter

A

,

Tomer

N

,

Fajadet

J.

How to set up an effective national primary angioplasty network: lessons learned from five European countries

.

EuroIntervention

2009

;

5

(

3

):

299

,301–309.

104

Nallamothu

BK

,

Krumholz

HM

,

Ko

DT

,

LaBresh

KA

,

Rathore

S

,

Roe

MT

,

Schwamm

L.

Development of systems of care for ST-elevation myocardial infarction patients: gaps, barriers, and implications

.

Circulation

2007

;

116

(

2

):

e68

–

e72

.

105

Rathore

SS

,

Curtis

JP

,

Chen

J

,

Wang

Y

,

Nallamothu

BK

,

Epstein

AJ

,

Krumholz

HM

,

National Cardiovascular Data Registry

.

Association of door-to-balloon time and mortality in patients admitted to hospital with ST elevation myocardial infarction: national cohort study

.

BMJ

2009

;

338

:

b1807

.

106

Nielsen

PH

,

Terkelsen

CJ

,

Nielsen

TT

,

Thuesen

L

,

Krusell

LR

,

Thayssen

P

,

Kelbaek

H

,

Abildgaard

U

,

Villadsen

AB

,

Andersen

HR

,

Maeng

M.

System delay and timing of intervention in acute myocardial infarction (from the Danish Acute Myocardial Infarction-2 [DANAMI-2] trial)

.

Am J Cardiol

2011

;

108

(

6

):

776

–

781

.

107

Pinto

DS

,

Kirtane

AJ

,

Nallamothu

BK

,

Murphy

SA

,

Cohen

DJ

,

Laham

RJ

,

Cutlip

DE

,

Bates

ER

,

Frederick

PD

,

Miller

DP

,

Carrozza

JP

,

Antman

EM

,

Cannon

CP

,

Gibson

CM.

Hospital delays in reperfusion for ST-elevation myocardial infarction: implications when selecting a reperfusion strategy

.

Circulation

2006

;

114

(

19

):

2019

–

2025

.

108

Widimsky

P

,

Fajadet

J

,

Danchin

N

,

Wijns

W.

"Stent 4 Life" targeting PCI at all who will benefit the most. A joint project between EAPCI, Euro-PCR, EUCOMED and the ESC Working Group on Acute Cardiac Care

.

EuroIntervention

2009

;

4

(

5

):

555

,557.

109

Steg

PG

,

Cambou

JP

,

Goldstein

P

,

Durand

E

,

Sauval

P

,

Kadri

Z

,

Blanchard

D

,

Lablanche

JM

,

Gueret

P

,

Cottin

Y

,

Juliard

JM

,

Hanania

G

,

Vaur

L

,

Danchin

N

,

USIC Investigators

.

Bypassing the emergency room reduces delays and mortality in ST elevation myocardial infarction: the USIC 2000 registry

.

Heart

2006

;

92

(

10

):

1378

–

1383

.

110

Baran

KW

,

Kamrowski

KA

,

Westwater

JJ

,

Tschida

VH

,

Alexander

CF

,

Beahrs

MM

,

Biggs

TA

,

Koller

PT

,

Mahoney

BD

,

Murray

ST

,

Raya

TE

,

Rusterholz

PK

,

Valeti

US

,

Wiberg

TA.

Very rapid treatment of ST-segment-elevation myocardial infarction: utilizing prehospital electrocardiograms to bypass the emergency department

.

Circ Cardiovasc Qual Outcomes

2010

;

3

(

4

):

431

–

437

.

111

Thiemann

DR

,

Coresh

J

,

Oetgen

WJ

,

Powe

NR.

The association between hospital volume and survival after acute myocardial infarction in elderly patients

.

N Engl J Med

1999

;

340

(

21

):

1640

–

1648

.

112

West

RM

,

Cattle

BA

,

Bouyssie

M

,

Squire

I

,

de Belder

M

,

Fox

KA

,

Boyle

R

,

McLenachan

JM

,

Batin

PD

,

Greenwood

DC

,

Gale

CP.

Impact of hospital proportion and volume on primary percutaneous coronary intervention performance in England and Wales

.

Eur Heart J

2011

;

32

(

6

):

706

–

711

.

113

Zijlstra

F

,

Hoorntje

JC

,

de Boer

MJ

,

Reiffers

S

,

Miedema

K

,

Ottervanger

JP

,

van 't Hof

AW

,

Suryapranata

H.

Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction

.

N Engl J Med

1999

;

341

(

19

):

1413

–

1419

.

114

Keeley

EC

,

Boura

JA

,

Grines

CL.

Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials

.

Lancet

2003

;

361

(

9351

):

13

–

20

.

115

Widimsky

P

,

Budesinsky

T

,

Vorac

D

,

Groch

L

,

Zelizko

M

,

Aschermann

M

,

Branny

M

,

St'asek

J

,

Formanek

P

,

'PRAGUE' Study Group Investigators

.

Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction. Final results of the randomized national multicentre trial—PRAGUE-2

.

Eur Heart J

2003

;

24

(

1

):

94

–

104

.

116

Andersen

HR

,

Nielsen

TT

,

Rasmussen

K

,

Thuesen

L

,

Kelbaek

H

,

Thayssen

P

,

Abildgaard

U

,

Pedersen

F

,

Madsen

JK

,

Grande

P

,

Villadsen

AB

,

Krusell

LR

,

Haghfelt

T

,

Lomholt

P

,

Husted

SE

,

Vigholt

E

,

Kjaergard

HK

,

Mortensen

LS

,

DANAMI-2 Investigators

.

A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction

.

N Engl J Med

2003

;

349

(

8

):

733

–

742

.

117

Nallamothu

BK

,

Bates

ER.

Percutaneous coronary intervention versus fibrinolytic therapy in acute myocardial infarction: is timing (almost) everything?

Am J Cardiol

2003

;

92

(

7

):

824

–

826

.

118

Betriu

A

,

Masotti

M.

Comparison of mortality rates in acute myocardial infarction treated by percutaneous coronary intervention versus fibrinolysis

.

Am J Cardiol

2005

;

95

(

1

):

100

–

101

.

119

Boersma

E

,

Primary Coronary Angioplasty vs Thrombolysis Group

.

Does time matter? A pooled analysis of randomized clinical trials comparing primary percutaneous coronary intervention and in-hospital fibrinolysis in acute myocardial infarction patients

.

Eur Heart J

2006

;

27

(

7

):

779

–

788

.

120

Pinto

DS

,

Frederick

PD

,

Chakrabarti

AK

,

Kirtane

AJ

,

Ullman

E

,

Dejam

A

,

Miller

DP

,

Henry

TD

,

Gibson

CM

,

National Registry of Myocardial Infarction Investigators

.

Benefit of transferring ST-segment-elevation myocardial infarction patients for percutaneous coronary intervention compared with administration of onsite fibrinolytic declines as delays increase

.

Circulation

2011

;

124

(

23

):

2512

–

2521

.

121

Armstrong

PW

,

Gershlick

AH

,

Goldstein

P

,

Wilcox

R

,

Danays

T

,

Lambert

Y

,

Sulimov

V

,

Rosell Ortiz

F

,

Ostojic

M

,

Welsh

RC

,

Carvalho

AC

,

Nanas

J

,

Arntz

HR

,

Halvorsen

S

,

Huber

K

,

Grajek

S

,

Fresco

C

,

Bluhmki

E

,

Regelin

A

,

Vandenberghe

K

,

Bogaerts

K

,

Van de Werf

F

,

STREAM Investigative Team

.

Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction

.

N Engl J Med

2013

;

368

(

15

):

1379

–

1387

.

122

Task Force on the management of ST-segment elevationsacute myocardial infarction of the European Society of Cardiology (ESC)

,

Steg

PG

,

James

SK

,

Atar

D

,

Badano

LP

,

Blomstrom-Lundqvist

C

,

Borger

MA

,

Di Mario

C

,

Dickstein

K

,

Ducrocq

G

,

Fernandez-Aviles

F

,

Gershlick

AH

,

Giannuzzi

P

,

Halvorsen

S

,

Huber

K

,

Juni

P

,

Kastrati

A

,

Knuuti

J

,

Lenzen

MJ

,

Mahaffey

KW

,

Valgimigli

M

,

van 't Hof

A

,

Widimsky

P

,

Zahger

D.

ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation

.

Eur Heart J

2012

;

33

(

20

):

2569

–

2619

.

123

Morrison

LJ

,

Verbeck

PR

,

McDonald

AC

,

Sawadsky

BV

,

Cook

DJ.

Mortality and prehospital thrombolysis for acute myocardial infarction: a meta-analysis

.

JAMA

2000

;

283

(

20

):

2686

–

2692

.

124

Gershlick

AH

,

Stephens-Lloyd

A

,

Hughes

S

,

Abrams

KR

,

Stevens

SE

,

Uren

NG

,

de Belder

A

,

Davis

J

,

Pitt

M

,

Banning

A

,

Baumbach

A

,

Shiu

MF

,

Schofield

P

,

Dawkins

KD

,

Henderson

RA

,

Oldroyd

KG

,

Wilcox

R

,

REACT Trial Investigators

.

Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction

.

N Engl J Med

2005

;

353

(

26

):

2758

–

2768

.

125

Madan

M

,

Halvorsen

S

,

Di Mario

C

,

Tan

M

,

Westerhout

CM

,

Cantor

WJ

,

Le May

MR

,

Borgia

F

,

Piscione

F

,

Scheller

B

,

Armstrong

PW

,

Fernandez-Aviles

F

,

Sanchez

PL

,

Graham

JJ

,

Yan

AT

,

Goodman

SG.

Relationship between time to invasive assessment and clinical outcomes of patients undergoing an early invasive strategy after fibrinolysis for ST-segment elevation myocardial infarction: a patient-level analysis of the randomized early routine invasive clinical trials

.

JACC Cardiovasc Interv

2015

;

8

(1 Pt B)

:

166

–

174

.

126

Cantor

WJ

,

Fitchett

D

,

Borgundvaag

B

,

Ducas

J

,

Heffernan

M

,

Cohen

EA

,

Morrison

LJ

,

Langer

A

,

Dzavik

V

,

Mehta

SR

,

Lazzam

C

,

Schwartz

B

,

Casanova

A

,

Goodman

SG

,

TRANSFER-AMI Trial Investigators

.

Routine early angioplasty after fibrinolysis for acute myocardial infarction

.

N Engl J Med

2009

;

360

(

26

):

2705

–

2718

.

127

Di Mario

C

,

Dudek

D

,

Piscione

F

,

Mielecki

W

,

Savonitto

S

,

Murena

E

,

Dimopoulos

K

,

Manari

A

,

Gaspardone

A

,

Ochala

A

,

Zmudka

K

,

Bolognese

L

,

Steg

PG

,

Flather

M

,

CARESS AMI Investigators

.

Immediate angioplasty versus standard therapy with rescue 3 angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI): an open, prospective, randomised, multicentre trial

.

Lancet

2008

;

371

(

9612

):

559

–

568

.

128

Bohmer

E

,

Hoffmann

P

,

Abdelnoor

M

,

Arnesen

H

,

Halvorsen

S.

Efficacy and safety of immediate angioplasty versus ischemia-guided management after thrombolysis in acute myocardial infarction in areas with very long transfer distances. Results of the NORDISTEMI (NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction)

.

J Am Coll Cardiol

2010

;

55

(

2

):

102

–

110

.

129

Borgia

F

,

Goodman

SG

,

Halvorsen

S

,

Cantor

WJ

,

Piscione

F

,

Le May

MR

,

Fernandez-Aviles

F

,

Sanchez

PL

,

Dimopoulos

K

,

Scheller

B

,

Armstrong

PW

,

Di Mario

C.

Early routine percutaneous coronary intervention after fibrinolysis vs. standard therapy in ST-segment elevation myocardial infarction: a meta-analysis

.

Eur Heart J

2010

;

31

(

17

):

2156

–

2169

.

130

D'Souza

SP

,

Mamas

MA

,

Fraser

DG

,

Fath-Ordoubadi

F.

Routine early coronary angioplasty versus ischaemia-guided angioplasty after thrombolysis in acute ST-elevation myocardial infarction: a meta-analysis

.

Eur Heart J

2011

;

32

(

8

):

972

–

982

.

131

Neeland

IJ

,

Kontos

MC

,

de Lemos

JA.

Evolving considerations in the management of patients with left bundle branch block and suspected myocardial infarction

.

J Am Coll Cardiol

2012

;

60

(

2

):

96

–

105

.

132

Liakopoulos

V

,

Kellerth

T

,

Christensen

K.

Left bundle branch block and suspected myocardial infarction: does chronicity of the branch block matter?

Eur Heart J Acute Cardiovasc Care

2013

;

2

(

2

):

182

–

189

.

133

Schomig

A

,

Mehilli

J

,

Antoniucci

D

,

Ndrepepa

G

,

Markwardt

C

,

Di Pede

F

,

Nekolla

SG

,

Schlotterbeck

K

,

Schuhlen

H

,

Pache

J

,

Seyfarth

M

,

Martinoff

S

,

Benzer

W

,

Schmitt

C

,

Dirschinger

J

,

Schwaiger

M

,

Kastrati

A

,

Beyond 12 hours Reperfusion Alternative Evaluation Trial Investigators

.

Mechanical reperfusion in patients with acute myocardial infarction presenting more than 12 hours from symptom onset: a randomized controlled trial

.

JAMA

2005

;

293

(

23

):

2865

–

2872

.

134

Ndrepepa

G

,

Kastrati

A

,

Mehilli

J

,

Antoniucci

D

,

Schomig

A.

Mechanical reperfusion and long-term mortality in patients with acute myocardial infarction presenting 12 to 48 hours from onset of symptoms

.

JAMA

2009

;

301

(

5

):

487

–

488

.

135

Hochman

JS

,

Lamas

GA

,

Buller

CE

,

Dzavik

V

,

Reynolds

HR

,

Abramsky

SJ

,

Forman

S

,

Ruzyllo

W

,

Maggioni

AP

,

White

H

,

Sadowski

Z

,

Carvalho

AC

,

Rankin

JM

,

Renkin

JP

,

Steg

PG

,

Mascette

AM

,

Sopko

G

,

Pfisterer

ME

,

Leor

J

,

Fridrich

V

,

Mark

DB

,

Knatterud

GL

,

Occluded Artery Trial Investigators

.

Coronary intervention for persistent occlusion after myocardial infarction

.

N Engl J Med

2006

;

355

(

23

):

2395

–

2407

.

136

Menon

V

,

Pearte

CA

,

Buller

CE

,

Steg

PG

,

Forman

SA

,

White

HD

,

Marino

PN

,

Katritsis

DG

,

Caramori

P

,

Lasevitch

R

,

Loboz-Grudzien

K

,

Zurakowski

A

,

Lamas

GA

,

Hochman

JS.

Lack of benefit from percutaneous intervention of persistently occluded infarct arteries after the acute phase of myocardial infarction is time independent: insights from Occluded Artery Trial

.

Eur Heart J

2009

;

30

(

2

):

183

–

191

.

137

Ioannidis

JP

,

Katritsis

DG.

Percutaneous coronary intervention for late reperfusion after myocardial infarction in stable patients

.

Am Heart J

2007

;

154

(

6

):

1065

–

1071

.

138

Boersma

E

,

Maas

ACP

,

Deckers

JW

,

Simoons

ML.

Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour

.

Lancet

1996

;

348

(

9030

):

771

–

775

.

139

Cucherat

M

,

Bonnefoy

E

,

Tremeau

G.

Primary angioplasty versus intravenous thrombolysis for acute myocardial infarction

.

Cochrane Database Syst Rev

2003

;

3

:

CD001560

.

140

Dalby

M

,

Bouzamondo

A

,

Lechat

P

,

Montalescot

G.

Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: a meta-analysis

.

Circulation

2003

;

108

(

15

):

1809

–

1814

.

141

Gierlotka

M

,

Gasior

M

,

Wilczek

K

,

Hawranek

M

,

Szkodzinski

J

,

Paczek

P

,

Lekston

A

,

Kalarus

Z

,

Zembala

M

,

Polonski

L.

Reperfusion by primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction within 12 to 24 hours of the onset of symptoms (from a prospective national observational study [PL-ACS])

.

Am J Cardiol

2011

;

107

(

4

):

501

–

508

.

142

Busk

M

,

Kaltoft

A

,

Nielsen

SS

,

Bottcher

M

,

Rehling

M

,

Thuesen

L

,

Botker

HE

,

Lassen

JF

,

Christiansen

EH

,

Krusell

LR

,

Andersen

HR

,

Nielsen

TT

,

Kristensen

SD.

Infarct size and myocardial salvage after primary angioplasty in patients presenting with symptoms for <12 h vs. 12-72 h

.

Eur Heart J

2009

;

30

(

11

):

1322

–

1330

.

143

Valgimigli

M

,

Gagnor

A

,

Calabro

P

,

Frigoli

E

,

Leonardi

S

,

Zaro

T

,

Rubartelli

P

,

Briguori

C

,

Ando

G

,

Repetto

A

,

Limbruno

U

,

Cortese

B

,

Sganzerla

P

,

Lupi

A

,

Galli

M

,

Colangelo

S

,

Ierna

S

,

Ausiello

A

,

Presbitero

P

,

Sardella

G

,

Varbella

F

,

Esposito

G

,

Santarelli

A

,

Tresoldi

S

,

Nazzaro

M

,

Zingarelli

A

,

de Cesare

N

,

Rigattieri

S

,

Tosi

P

,

Palmieri

C

,

Brugaletta

S

,

Rao

SV

,

Heg

D

,

Rothenbuhler

M

,

Vranckx

P

,

Juni

P

,

MATRIX Investigators

.

Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial

.

Lancet

2015

;

385

(

9986

):

2465

–

2476

.

144

Jolly

SS

,

Yusuf

S

,

Cairns

J

,

Niemela

K

,

Xavier

D

,

Widimsky

P

,

Budaj

A

,

Niemela

M

,

Valentin

V

,

Lewis

BS

,

Avezum

A

,

Steg

PG

,

Rao

SV

,

Gao

P

,

Afzal

R

,

Joyner

CD

,

Chrolavicius

S

,

Mehta

SR

,

RIVAL Trial Group

.

Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial

.

Lancet

2011

;

377

(

9775

):

1409

–

1420

.

145

Romagnoli

E

,

Biondi-Zoccai

G

,

Sciahbasi

A

,

Politi

L

,

Rigattieri

S

,

Pendenza

G

,

Summaria

F

,

Patrizi

R

,

Borghi

A

,

Di Russo

C

,

Moretti

C

,

Agostoni

P

,

Loschiavo

P

,

Lioy

E

,

Sheiban

I

,

Sangiorgi

G.

Radial versus femoral randomized investigation in ST-segment elevation acute coronary syndrome: the RIFLE-STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome) study

.

J Am Coll Cardiol

2012

;

60

(

24

):

2481

–

2489

.

146

Nordmann

AJ

,

Hengstler

P

,

Harr

T

,

Young

J

,

Bucher

HC.

Clinical outcomes of primary stenting versus balloon angioplasty in patients with myocardial infarction: a meta-analysis of randomized controlled trials

.

Am J Med

2004

;

116

(

4

):

253

–

262

.

147

Stone

GW

,

Grines

CL

,

Cox

DA

,

Garcia

E

,

Tcheng

JE

,

Griffin

JJ

,

Guagliumi

G

,

Stuckey

T

,

Turco

M

,

Carroll

JD

,

Rutherford

BD

,

Lansky

AJ

,

Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Investigators

.

Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction

.

N Engl J Med

2002

;

346

(

13

):

957

–

966

.

148

Kastrati

A

,

Dibra

A

,

Spaulding

C

,

Laarman

GJ

,

Menichelli

M

,

Valgimigli

M

,

Di Lorenzo

E

,

Kaiser

C

,

Tierala

I

,

Mehilli

J

,

Seyfarth

M

,

Varenne

O

,

Dirksen

MT

,

Percoco

G

,

Varricchio

A

,

Pittl

U

,

Syvanne

M

,

Suttorp

MJ

,

Violini

R

,

Schomig

A.

Meta-analysis of randomized trials on drug-eluting stents vs. bare-metal stents in patients with acute myocardial infarction

.

Eur Heart J

2007

;

28

(

22

):

2706

–

2713

.

149

Raber

L

,

Kelbaek

H

,

Ostojic

M

,

Baumbach

A

,

Heg

D

,

Tuller

D

,

von Birgelen

C

,

Roffi

M

,

Moschovitis

A

,

Khattab

AA

,

Wenaweser

P

,

Bonvini

R

,

Pedrazzini

G

,

Kornowski

R

,

Weber

K

,

Trelle

S

,

Luscher

TF

,

Taniwaki

M

,

Matter

CM

,

Meier

B

,

Juni

P

,

Windecker

S

,

COMFORTABLE AMI Trial Investigators

.

Effect of biolimus-eluting stents with biodegradable polymer vs bare-metal stents on cardiovascular events among patients with acute myocardial infarction: the COMFORTABLE AMI randomized trial

.

JAMA

2012

;

308

(

8

):

777

–

787

.

150

Sabate

M

,

Cequier

A

,

Iniguez

A

,

Serra

A

,

Hernandez-Antolin

R

,

Mainar

V

,

Valgimigli

M

,

Tespili

M

,

den Heijer

P

,

Bethencourt

A

,

Vazquez

N

,

Gomez-Hospital

JA

,

Baz

JA

,

Martin-Yuste

V

,

van Geuns

RJ

,

Alfonso

F

,

Bordes

P

,

Tebaldi

M

,

Masotti

M

,

Silvestro

A

,

Backx

B

,

Brugaletta

S

,

van Es

GA

,

Serruys

PW.

Everolimus-eluting stent versus bare-metal stent in ST-segment elevation myocardial infarction (EXAMINATION): 1 year results of a randomised controlled trial

.

Lancet

2012

;

380

(

9852

):

1482

–

1490

.

151

Sabate

M

,

Brugaletta

S

,

Cequier

A

,

Iniguez

A

,

Serra

A

,

Jimenez-Quevedo

P

,

Mainar

V

,

Campo

G

,

Tespili

M

,

den Heijer

P

,

Bethencourt

A

,

Vazquez

N

,

van Es

GA

,

Backx

B

,

Valgimigli

M

,

Serruys

PW.

Clinical outcomes in patients with ST-segment elevation myocardial infarction treated with everolimus-eluting stents versus bare-metal stents (EXAMINATION): 5-year results of a randomised trial

.

Lancet

2016

;

387

(

10016

):

357

–

366

.

152

Bonaa

KH

,

Mannsverk

J

,

Wiseth

R

,

Aaberge

L

,

Myreng

Y

,

Nygard

O

,

Nilsen

DW

,

Klow

NE

,

Uchto

M

,

Trovik

T

,

Bendz

B

,

Stavnes

S

,

Bjornerheim

R

,

Larsen

AI

,

Slette

M

,

Steigen

T

,

Jakobsen

OJ

,

Bleie

O

,

Fossum

E

,

Hanssen

TA

,

Dahl-Eriksen

O

,

Njolstad

I

,

Rasmussen

K

,

Wilsgaard

T

,

Nordrehaug

JE

,

NORSTENT Investigators

.

Drug-eluting or bare-metal stents for coronary artery disease

.

N Engl J Med

2016

;

375

(

13

):

1242

–

1252

.

153

Carrick

D

,

Oldroyd

KG

,

McEntegart

M

,

Haig

C

,

Petrie

MC

,

Eteiba

H

,

Hood

S

,

Owens

C

,

Watkins

S

,

Layland

J

,

Lindsay

M

,

Peat

E

,

Rae

A

,

Behan

M

,

Sood

A

,

Hillis

WS

,

Mordi

I

,

Mahrous

A

,

Ahmed

N

,

Wilson

R

,

Lasalle

L

,

Genereux

P

,

Ford

I

,

Berry

C.

A randomized trial of deferred stenting versus immediate stenting to prevent no- or slow-reflow in acute ST-segment elevation myocardial infarction (DEFER-STEMI)

.

J Am Coll Cardiol

2014

;

63

(

20

):

2088

–

2098

.

154

Belle

L

,

Motreff

P

,

Mangin

L

,

Range

G

,

Marcaggi

X

,

Marie

A

,

Ferrier

N

,

Dubreuil

O

,

Zemour

G

,

Souteyrand

G

,

Caussin

C

,

Amabile

N

,

Isaaz

K

,

Dauphin

R

,

Koning

R

,

Robin

C

,

Faurie

B

,

Bonello

L

,

Champin

S

,

Delhaye

C

,

Cuilleret

F

,

Mewton

N

,

Genty

C

,

Viallon

M

,

Bosson

JL

,

Croisille

P

,

MIMI Investigators

.

Comparison of immediate with delayed stenting using the minimalist immediate mechanical intervention approach in acute ST-segment-elevation myocardial infarction: the MIMI Study

.

Circ Cardiovasc Interv

2016

;

9

(

3

):

e003388

.

155

Kelbaek

H

,

Hofsten

DE

,

Kober

L

,

Helqvist

S

,

Klovgaard

L

,

Holmvang

L

,

Jorgensen

E

,

Pedersen

F

,

Saunamaki

K

,

De Backer

O

,

Bang

LE

,

Kofoed

KF

,

Lonborg

J

,

Ahtarovski

K

,

Vejlstrup

N

,

Botker

HE

,

Terkelsen

CJ

,

Christiansen

EH

,

Ravkilde

J

,

Tilsted

HH

,

Villadsen

AB

,

Aaroe

J

,

Jensen

SE

,

Raungaard

B

,

Jensen

LO

,

Clemmensen

P

,

Grande

P

,

Madsen

JK

,

Torp-Pedersen

C

,

Engstrom

T.

Deferred versus conventional stent implantation in patients with ST-segment elevation myocardial infarction (DANAMI 3-DEFER): an open-label, randomised controlled trial

.

Lancet

2016

;

387

(

10034

):

2199

–

2206

.

156

Burzotta

F

,

De Vita

M

,

Gu

YL

,

Isshiki

T

,

Lefevre

T

,

Kaltoft

A

,

Dudek

D

,

Sardella

G

,

Orrego

PS

,

Antoniucci

D

,

De Luca

L

,

Biondi-Zoccai

GG

,

Crea

F

,

Zijlstra

F.

Clinical impact of thrombectomy in acute ST-elevation myocardial infarction: an individual patient-data pooled analysis of 11 trials

.

Eur Heart J

2009

;

30

(

18

):

2193

–

2203

.

157

Frobert

O

,

Lagerqvist

B

,

Olivecrona

GK

,

Omerovic

E

,

Gudnason

T

,

Maeng

M

,

Aasa

M

,

Angeras

O

,

Calais

F

,

Danielewicz

M

,

Erlinge

D

,

Hellsten

L

,

Jensen

U

,

Johansson

AC

,

Karegren

A

,

Nilsson

J

,

Robertson

L

,

Sandhall

L

,

Sjogren

I

,

Ostlund

O

,

Harnek

J

,

James

SK

,

TASTE Trial

.

Thrombus aspiration during ST-segment elevation myocardial infarction

.

N Engl J Med

2013

;

369

(

17

):

1587

–

1597

.

158

Lagerqvist

B

,

Frobert

O

,

Olivecrona

GK

,

Gudnason

T

,

Maeng

M

,

Alstrom

P

,

Andersson

J

,

Calais

F

,

Carlsson

J

,

Collste

O

,

Gotberg

M

,

Hardhammar

P

,

Ioanes

D

,

Kallryd

A

,

Linder

R

,

Lundin

A

,

Odenstedt

J

,

Omerovic

E

,

Puskar

V

,

Todt

T

,

Zelleroth

E

,

Ostlund

O

,

James

SK.

Outcomes 1 year after thrombus aspiration for myocardial infarction

.

N Engl J Med

2014

;

371

(

12

):

1111

–

1120

.

159

Jolly

SS

,

Cairns

JA

,

Yusuf

S

,

Meeks

B

,

Pogue

J

,

Rokoss

MJ

,

Kedev

S

,

Thabane

L

,

Stankovic

G

,

Moreno

R

,

Gershlick

A

,

Chowdhary

S

,

Lavi

S

,

Niemela

K

,

Steg

PG

,

Bernat

I

,

Xu

Y

,

Cantor

WJ

,

Overgaard

CB

,

Naber

CK

,

Cheema

AN

,

Welsh

RC

,

Bertrand

OF

,

Avezum

A

,

Bhindi

R

,

Pancholy

S

,

Rao

SV

,

Natarajan

MK

,

ten Berg

JM

,

Shestakovska

O

,

Gao

P

,

Widimsky

P

,

Dzavik

V

,

TOTAL Investigators

.

Randomized trial of primary PCI with or without routine manual thrombectomy

.

N Engl J Med

2015

;

372

(

15

):

1389

–

1398

.

160

Jolly

SS

,

Cairns

JA

,

Yusuf

S

,

Rokoss

MJ

,

Gao

P

,

Meeks

B

,

Kedev

S

,

Stankovic

G

,

Moreno

R

,

Gershlick

A

,

Chowdhary

S

,

Lavi

S

,

Niemela

K

,

Bernat

I

,

Cantor

WJ

,

Cheema

AN

,

Steg

PG

,

Welsh

RC

,

Sheth

T

,

Bertrand

OF

,

Avezum

A

,

Bhindi

R

,

Natarajan

MK

,

Horak

D

,

Leung

RC

,

Kassam

S

,

Rao

SV

,

El-Omar

M

,

Mehta

SR

,

Velianou

JL

,

Pancholy

S

,

Dzavik

V

,

TOTAL Investigators

.

Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial

.

Lancet

2016

;

387

(

10014

):

127

–

135

.

161

Jolly

SS

,

Cairns

JA

,

Yusuf

S

,

Meeks

B

,

Gao

P

,

Hart

RG

,

Kedev

S

,

Stankovic

G

,

Moreno

R

,

Horak

D

,

Kassam

S

,

Rokoss

MJ

,

Leung

RC

,

El-Omar

M

,

Romppanen

HO

,

Alazzoni

A

,

Alak

A

,

Fung

A

,

Alexopoulos

D

,

Schwalm

JD

,

Valettas

N

,

Dzavik

V

,

TOTAL Investigators

.

Stroke in the TOTAL trial: a randomized trial of routine thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction

.

Eur Heart J

2015

;

36

(

35

):

2364

–

2372

.

162

Jolly

SS

,

James

S

,

Dzavik

V

,

Cairns

JA

,

Mahmoud

KD

,

Zijlstra

F

,

Yusuf

S

,

Olivecrona

GK

,

Renlund

H

,

Gao

P

,

Lagerqvist

B

,

Alazzoni

A

,

Kedev

S

,

Stankovic

G

,

Meeks

B

,

Frobert

O.

Thrombus aspiration in ST-segment-elevation myocardial infarction. An individual patient meta-analysis: Thrombectomy Trialists Collaboration

.

Circulation

2017

;

135

(

2

):

143

–

152

.

163

Sorajja

P

,

Gersh

BJ

,

Cox

DA

,

McLaughlin

MG

,

Zimetbaum

P

,

Costantini

C

,

Stuckey

T

,

Tcheng

JE

,

Mehran

R

,

Lansky

AJ

,

Grines

CL

,

Stone

GW.

Impact of multivessel disease on reperfusion success and clinical outcomes in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction

.

Eur Heart J

2007

;

28

(

14

):

1709

–

1716

.

164

Dziewierz

A

,

Siudak

Z

,

Rakowski

T

,

Zasada

W

,

Dubiel

JS

,

Dudek

D.

Impact of multivessel coronary artery disease and noninfarct-related artery revascularization on outcome of patients with ST-elevation myocardial infarction transferred for primary percutaneous coronary intervention (from the EUROTRANSFER Registry)

.

Am J Cardiol

2010

;

106

(

3

):

342

–

347

.

165

Cavender

MA

,

Milford-Beland

S

,

Roe

MT

,

Peterson

ED

,

Weintraub

WS

,

Rao

SV.

Prevalence, predictors, and in-hospital outcomes of non-infarct artery intervention during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (from the National Cardiovascular Data Registry)

.

Am J Cardiol

2009

;

104

(

4

):

507

–

513

.

166

Hannan

EL

,

Samadashvili

Z

,

Walford

G

,

Holmes

DR

Jr,

Jacobs

AK

,

Stamato

NJ

,

Venditti

FJ

,

Sharma

S

,

King

SB

3rd.

Culprit vessel percutaneous coronary intervention versus multivessel and staged percutaneous coronary intervention for ST-segment elevation myocardial infarction patients with multivessel disease

.

JACC Cardiovasc Interv

2010

;

3

(

1

):

22

–

31

.

167

Politi

L

,

Sgura

F

,

Rossi

R

,

Monopoli

D

,

Guerri

E

,

Leuzzi

C

,

Bursi

F

,

Sangiorgi

GM

,

Modena

MG.

A randomised trial of target-vessel versus multi-vessel revascularisation in ST-elevation myocardial infarction: major adverse cardiac events during long-term follow-up

.

Heart

2010

;

96

(

9

):

662

–

667

.

168

Wald

DS

,

Morris

JK

,

Wald

NJ

,

Chase

AJ

,

Edwards

RJ

,

Hughes

LO

,

Berry

C

,

Oldroyd

KG

,

PRAMI Investigators

.

Randomized trial of preventive angioplasty in myocardial infarction

.

N Engl J Med

2013

;

369

(

12

):

1115

–

1123

.

169

Gershlick

AH

,

Khan

JN

,

Kelly

DJ

,

Greenwood

JP

,

Sasikaran

T

,

Curzen

N

,

Blackman

DJ

,

Dalby

M

,

Fairbrother

KL

,

Banya

W

,

Wang

D

,

Flather

M

,

Hetherington

SL

,

Kelion

AD

,

Talwar

S

,

Gunning

M

,

Hall

R

,

Swanton

H

,

McCann

GP.

Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease: the CvLPRIT trial

.

J Am Coll Cardiol

2015

;

65

(

10

):

963

–

972

.

170

Engstrom

T

,

Kelbaek

H

,

Helqvist

S

,

Hofsten

DE

,

Klovgaard

L

,

Holmvang

L

,

Jorgensen

E

,

Pedersen

F

,

Saunamaki

K

,

Clemmensen

P

,

De Backer

O

,

Ravkilde

J

,

Tilsted

HH

,

Villadsen

AB

,

Aaroe

J

,

Jensen

SE

,

Raungaard

B

,

Kober

L

,

DANAMI-PRIMULTI Investigators

.

Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3-PRIMULTI): an open-label, randomised controlled trial

.

Lancet

2015

;

386

(

9994

):

665

–

671

.

171

Smits

PC

,

Abdel-Wahab

M

,

Neumann

FJ

,

Boxma-de Klerk

BM

,

Lunde

K

,

Schotborgh

CE

,

Piroth

Z

,

Horak

D

,

Wlodarczak

A

,

Ong

PJ

,

Hambrecht

R

,

Angeras

O

,

Richardt

G

,

Omerovic

E

,

Compare-Acute Investigators

.

Fractional flow reserve-guided multivessel angioplasty in myocardial infarction

.

N Engl J Med

2017

;

376

(

13

):

1234

–

1244

.

172

Moreno

R

,

Mehta

SR.

Nonculprit vessel intervention: let's COMPLETE the evidence

.

Rev Esp Cardiol (English Ed)

2017

;

70

:

418

–

420

.

173

Bangalore

S

,

Toklu

B

,

Wetterslev

J.

Complete versus culprit-only revascularization for ST-segment-elevation myocardial infarction and multivessel disease: a meta-analysis and trial sequential analysis of randomized trials

.

Circ Cardiovasc Interv

2015

;

8

(

4

):

e002142

.

174

Elgendy

IY

,

Mahmoud

AN

,

Kumbhani

DJ

,

Bhatt

DL

,

Bavry

AA.

Complete or culprit-only revascularization for patients with multivessel coronary artery disease undergoing percutaneous coronary intervention: a pairwise and network meta-analysis of randomized trials

.

JACC Cardiovasc Interv

2017

;

10

(

4

):

315

–

324

.

175

Patel

MR

,

Smalling

RW

,

Thiele

H

,

Barnhart

HX

,

Zhou

Y

,

Chandra

P

,

Chew

D

,

Cohen

M

,

French

J

,

Perera

D

,

Ohman

EM.

Intra-aortic balloon counterpulsation and infarct size in patients with acute anterior myocardial infarction without shock: the CRISP AMI randomized trial

.

JAMA

2011

;

306

(

12

):

1329

–

1337

.

176

Sjauw

KD

,

Engstrom

AE

,

Vis

MM

,

van der Schaaf

RJ

,

Baan

J

Jr,

Koch

KT

,

de Winter

RJ

,

Piek

JJ

,

Tijssen

JG

,

Henriques

JP.

A systematic review and meta-analysis of intra-aortic balloon pump therapy in ST-elevation myocardial infarction: should we change the guidelines?

Eur Heart J

2009

;

30

(

4

):

459

–

468

.

177

Thiele

H

,

Zeymer

U

,

Neumann

FJ

,

Ferenc

M

,

Olbrich

HG

,

Hausleiter

J

,

Richardt

G

,

Hennersdorf

M

,

Empen

K

,

Fuernau

G

,

Desch

S

,

Eitel

I

,

Hambrecht

R

,

Fuhrmann

J

,

Bohm

M

,

Ebelt

H

,

Schneider

S

,

Schuler

G

,

Werdan

K

,

IABP-SHOCK II Trial Investigators

.

Intraaortic balloon support for myocardial infarction with cardiogenic shock

.

N Engl J Med

2012

;

367

(

14

):

1287

–

1296

.

178

Stefanini

GG

,

Byrne

RA

,

Serruys

PW

,

de Waha

A

,

Meier

B

,

Massberg

S

,

Juni

P

,

Schomig

A

,

Windecker

S

,

Kastrati

A.

Biodegradable polymer drug-eluting stents reduce the risk of stent thrombosis at 4 years in patients undergoing percutaneous coronary intervention: a pooled analysis of individual patient data from the ISAR-TEST 3, ISAR-TEST 4, and LEADERS randomized trials

.

Eur Heart J

2012

;

33

(

10

):

1214

–

1222

.

179

Palmerini

T

,

Biondi-Zoccai

G

,

Della Riva

D

,

Mariani

A

,

Sabate

M

,

Valgimigli

M

,

Frati

G

,

Kedhi

E

,

Smits

PC

,

Kaiser

C

,

Genereux

P

,

Galatius

S

,

Kirtane

AJ

,

Stone

GW.

Clinical outcomes with drug-eluting and bare-metal stents in patients with ST-segment elevation myocardial infarction: evidence from a comprehensive network meta-analysis

.

J Am Coll Cardiol

2013

;

62

(

6

):

496

–

504

.

180

Karrowni

W

,

Vyas

A

,

Giacomino

B

,

Schweizer

M

,

Blevins

A

,

Girotra

S

,

Horwitz

PA.

Radial versus femoral access for primary percutaneous interventions in ST-segment elevation myocardial infarction patients: a meta-analysis of randomized controlled trials

.

JACC Cardiovasc Interv

2013

;

6

(

8

):

814

–

823

.

181

Zeymer

U

,

Hohlfeld

T

,

Vom Dahl

J

,

Erbel

R

,

Munzel

T

,

Zahn

R

,

Roitenberg

A

,

Breitenstein

S

,

Pap

AF

,

Trenk

D.

Prospective, randomised trial of the time dependent antiplatelet effects of 500 mg and 250 mg acetylsalicylic acid i. v. and 300 mg p. o. in ACS (ACUTE)

.

Thromb Haemost

2017

;

117

(

3

):

625

–

635

.

182

Montalescot

G

,

van 't Hof

AW

,

Lapostolle

F

,

Silvain

J

,

Lassen

JF

,

Bolognese

L

,

Cantor

WJ

,

Cequier

A

,

Chettibi

M

,

Goodman

SG

,

Hammett

CJ

,

Huber

K

,

Janzon

M

,

Merkely

B

,

Storey

RF

,

Zeymer

U

,

Stibbe

O

,

Ecollan

P

,

Heutz

WM

,

Swahn

E

,

Collet

JP

,

Willems

FF

,

Baradat

C

,

Licour

M

,

Tsatsaris

A

,

Vicaut

E

,

Hamm

CW

,

ATLANTIC Investigators

.

Prehospital ticagrelor in ST-segment elevation myocardial infarction

.

N Engl J Med

2014

;

371

(

11

):

1016

–

1027

.

183

Koul

S

,

Smith

JG

,

Schersten

F

,

James

S

,

Lagerqvist

B

,

Erlinge

D.

Effect of upstream clopidogrel treatment in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

.

Eur Heart J

2011

;

32

(

23

):

2989

–

2997

.

184

Dorler

J

,

Edlinger

M

,

Alber

HF

,

Altenberger

J

,

Benzer

W

,

Grimm

G

,

Huber

K

,

Pachinger

O

,

Schuchlenz

H

,

Siostrzonek

P

,

Zenker

G

,

Weidinger

F

,

Austrian Acute PCI Investigators

.

Clopidogrel pre-treatment is associated with reduced in-hospital mortality in primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

.

Eur Heart J

2011

;

32

(

23

):2954–1961.

185

Zeymer

U

,

Arntz

HR

,

Mark

B

,

Fichtlscherer

S

,

Werner

G

,

Scholler

R

,

Zahn

R

,

Diller

F

,

Darius

H

,

Dill

T

,

Huber

K.

Efficacy and safety of a high loading dose of clopidogrel administered prehospitally to improve primary percutaneous coronary intervention in acute myocardial infarction: the randomized CIPAMI trial

.

Clin Res Cardiol

2012

;

101

(

4

):

305

–

312

.

186

Wiviott

SD

,

Braunwald

E

,

McCabe

CH

,

Montalescot

G

,

Ruzyllo

W

,

Gottlieb

S

,

Neumann

FJ

,

Ardissino

D

,

De Servi

S

,

Murphy

SA

,

Riesmeyer

J

,

Weerakkody

G

,

Gibson

CM

,

Antman

EM

,

TRITON-TIMI 38 Investigators

.

Prasugrel versus clopidogrel in patients with acute coronary syndromes

.

N Engl J Med

2007

;

357

(

20

):

2001

–

2015

.

187

Wallentin

L

,

Becker

RC

,

Budaj

A

,

Cannon

CP

,

Emanuelsson

H

,

Held

C

,

Horrow

J

,

Husted

S

,

James

S

,

Katus

H

,

Mahaffey

KW

,

Scirica

BM

,

Skene

A

,

Steg

PG

,

Storey

RF

,

Harrington

RA

PLATO Investigators

Freij

A

,

Thorsen

M.

Ticagrelor versus clopidogrel in patients with acute coronary syndromes

.

N Engl J Med

2009

;

361

(

11

):

1045

–

1057

.

188

Roe

MT

,

Armstrong

PW

,

Fox

KA

,

White

HD

,

Prabhakaran

D

,

Goodman

SG

,

Cornel

JH

,

Bhatt

DL

,

Clemmensen

P

,

Martinez

F

,

Ardissino

D

,

Nicolau

JC

,

Boden

WE

,

Gurbel

PA

,

Ruzyllo

W

,

Dalby

AJ

,

McGuire

DK

,

Leiva-Pons

JL

,

Parkhomenko

A

,

Gottlieb

S

,

Topacio

GO

,

Hamm

C

,

Pavlides

G

,

Goudev

AR

,

Oto

A

,

Tseng

CD

,

Merkely

B

,

Gasparovic

V

,

Corbalan

R

,

Cinteza

M

,

McLendon

RC

,

Winters

KJ

,

Brown

EB

,

Lokhnygina

Y

,

Aylward

PE

,

Huber

K

,

Hochman

JS

,

Ohman

EM

,

TRILOGY ACS Investigators

.

Prasugrel versus clopidogrel for acute coronary syndromes without revascularization

.

N Engl J Med

2012

;

367

(

14

):

1297

–

1309

.

189

Storey

RF

,

Becker

RC

,

Harrington

RA

,

Husted

S

,

James

SK

,

Cools

F

,

Steg

PG

,

Khurmi

NS

,

Emanuelsson

H

,

Cooper

A

,

Cairns

R

,

Cannon

CP

,

Wallentin

L.

Characterization of dyspnoea in PLATO study patients treated with ticagrelor or clopidogrel and its association with clinical outcomes

.

Eur Heart J

2011

;

32

(

23

):

2945

–

2953

.

190

Mehta

SR

,

Tanguay

JF

,

Eikelboom

JW

,

Jolly

SS

,

Joyner

CD

,

Granger

CB

,

Faxon

DP

,

Rupprecht

HJ

,

Budaj

A

,

Avezum

A

,

Widimsky

P

,

Steg

PG

,

Bassand

JP

,

Montalescot

G

,

Macaya

C

,

Di Pasquale

G

,

Niemela

K

,

Ajani

AE

,

White

HD

,

Chrolavicius

S

,

Gao

P

,

Fox

KA

,

Yusuf

S

,

CURRENT-OASIS Trial Investigators

.

Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial

.

Lancet

2010

;

376

(

9748

):

1233

–

1243

.

191

Bhatt

DL

,

Lincoff

AM

,

Gibson

CM

,

Stone

GW

,

McNulty

S

,

Montalescot

G

,

Kleiman

NS

,

Goodman

SG

,

White

HD

,

Mahaffey

KW

,

Pollack

CV

Jr,

Manoukian

SV

,

Widimsky

P

,

Chew

DP

,

Cura

F

,

Manukov

I

,

Tousek

F

,

Jafar

MZ

,

Arneja

J

,

Skerjanec

S

,

Harrington

RA

,

CHAMPION PLATFORM Investigators

.

Intravenous platelet blockade with cangrelor during PCI

.

N Engl J Med

2009

;

361

(

24

):

2330

–

2341

.

192

Harrington

RA

,

Stone

GW

,

McNulty

S

,

White

HD

,

Lincoff

AM

,

Gibson

CM

,

Pollack

CV

Jr,

Montalescot

G

,

Mahaffey

KW

,

Kleiman

NS

,

Goodman

SG

,

Amine

M

,

Angiolillo

DJ

,

Becker

RC

,

Chew

DP

,

French

WJ

,

Leisch

F

,

Parikh

KH

,

Skerjanec

S

,

Bhatt

DL.

Platelet inhibition with cangrelor in patients undergoing PCI

.

N Engl J Med

2009

;

361

(

24

):

2318

–

2329

.

193

Bhatt

DL

,

Stone

GW

,

Mahaffey

KW

,

Gibson

CM

,

Steg

PG

,

Hamm

CW

,

Price

MJ

,

Leonardi

S

,

Gallup

D

,

Bramucci

E

,

Radke

PW

,

Widimsky

P

,

Tousek

F

,

Tauth

J

,

Spriggs

D

,

McLaurin

BT

,

Angiolillo

DJ

,

Genereux

P

,

Liu

T

,

Prats

J

,

Todd

M

,

Skerjanec

S

,

White

HD

,

Harrington

RA

,

CHAMPION PHOENIX Investigators

.

Effect of platelet inhibition with cangrelor during PCI on ischemic events

.

N Engl J Med

2013

;

368

(

14

):

1303

–

1313

.

194

Steg

PG

,

Bhatt

DL

,

Hamm

CW

,

Stone

GW

,

Gibson

CM

,

Mahaffey

KW

,

Leonardi

S

,

Liu

T

,

Skerjanec

S

,

Day

JR

,

Iwaoka

RS

,

Stuckey

TD

,

Gogia

HS

,

Gruberg

L

,

French

WJ

,

White

HD

,

Harrington

RA

,

CHAMPION Investigators

.

Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data

.

Lancet

2013

;

382

(

9909

):

1981

–

1992

.

195

Ellis

SG

,

Tendera

M

,

de Belder

MA

,

van Boven

AJ

,

Widimsky

P

,

Janssens

L

,

Andersen

HR

,

Betriu

A

,

Savonitto

S

,

Adamus

J

,

Peruga

JZ

,

Kosmider

M

,

Katz

O

,

Neunteufl

T

,

Jorgova

J

,

Dorobantu

M

,

Grinfeld

L

,

Armstrong

P

,

Brodie

BR

,

Herrmann

HC

,

Montalescot

G

,

Neumann

FJ

,

Effron

MB

,

Barnathan

ES

,

Topol

EJ

,

FINESSE Investigators

.

Facilitated PCI in patients with ST-elevation myocardial infarction

.

N Engl J Med

2008

;

358

(

21

):

2205

–

2217

.

196

ten Berg

JM

,

van 't Hof

AW

,

Dill

T

,

Heestermans

T

,

van Werkum

JW

,

Mosterd

A

,

van Houwelingen

G

,

Koopmans

PC

,

Stella

PR

,

Boersma

E

,

Hamm

C.

Effect of early, pre-hospital initiation of high bolus dose tirofiban in patients with ST-segment elevation myocardial infarction on short- and long-term clinical outcome

.

J Am Coll Cardiol

2010

;

55

(

22

):

2446

–

2455

.

197

Stone

GW

,

Witzenbichler

B

,

Guagliumi

G

,

Peruga

JZ

,

Brodie

BR

,

Dudek

D

,

Kornowski

R

,

Hartmann

F

,

Gersh

BJ

,

Pocock

SJ

,

Dangas

G

,

Wong

SC

,

Kirtane

AJ

,

Parise

H

,

Mehran

R

,

HORIZONS-AMI Trial Investigators

.

Bivalirudin during primary PCI in acute myocardial infarction

.

N Engl J Med

2008

;

358

(

21

):

2218

–

2230

.

198

Friedland

S

,

Eisenberg

MJ

,

Shimony

A.

Meta-analysis of randomized controlled trials of intracoronary versus intravenous administration of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention for acute coronary syndrome

.

Am J Cardiol

2011

;

108

(

9

):

1244

–

1251

.

199

Yusuf

S

,

Mehta

SR

,

Chrolavicius

S

,

Afzal

R

,

Pogue

J

,

Granger

CB

,

Budaj

A

,

Peters

RJG

,

Bassand

JP

,

Wallentin

L

,

Joyner

C

,

Fox

KAA

,

OASIS-6 Trial Group

.

Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial

.

JAMA

2006

;

295

(

13

):

1519

–

1530

.

200

Montalescot

G

,

Zeymer

U

,

Silvain

J

,

Boulanger

B

,

Cohen

M

,

Goldstein

P

,

Ecollan

P

,

Combes

X

,

Huber

K

,

Pollack

C

Jr,

Benezet

JF

,

Stibbe

O

,

Filippi

E

,

Teiger

E

,

Cayla

G

,

Elhadad

S

,

Adnet

F

,

Chouihed

T

,

Gallula

S

,

Greffet

A

,

Aout

M

,

Collet

JP

,

Vicaut

E

,

ATOLL Investigators

.

Intravenous enoxaparin or unfractionated heparin in primary percutaneous coronary intervention for ST-elevation myocardial infarction: the international randomised open-label ATOLL trial

.

Lancet

2011

;

378

(

9792

):

693

–

703

.

201

Collet

JP

,

Huber

K

,

Cohen

M

,

Zeymer

U

,

Goldstein

P

,

Pollack

C

Jr,

Silvain

J

,

Henry

P

,

Varenne

O

,

Carrie

D

,

Coste

P

,

Angioi

M

,

Le Breton

H

,

Cayla

G

,

Elhadad

S

,

Teiger

E

,

Filippi

E

,

Aout

M

,

Vicaut

E

,

Montalescot

G

,

ATOLL Investigators

.

A direct comparison of intravenous enoxaparin with unfractionated heparin in primary percutaneous coronary intervention (from the ATOLL trial)

.

Am J Cardiol

2013

;

112

(

9

):

1367

–

1372

.

202

Silvain

J

,

Beygui

F

,

Barthelemy

O

,

Pollack

C

Jr,

Cohen

M

,

Zeymer

U

,

Huber

K

,

Goldstein

P

,

Cayla

G

,

Collet

JP

,

Vicaut

E

,

Montalescot

G.

Efficacy and safety of enoxaparin versus unfractionated heparin during percutaneous coronary intervention: systematic review and meta-analysis

.

BMJ

2012

;

344

:

e553

.

203

Steg

PG

,

van 't Hof

A

,

Hamm

CW

,

Clemmensen

P

,

Lapostolle

F

,

Coste

P

,

Ten Berg

J

,

Van Grunsven

P

,

Eggink

GJ

,

Nibbe

L

,

Zeymer

U

,

Campo dell' Orto

M

,

Nef

H

,

Steinmetz

J

,

Soulat

L

,

Huber

K

,

Deliargyris

EN

,

Bernstein

D

,

Schuette

D

,

Prats

J

,

Clayton

T

,

Pocock

S

,

Hamon

M

,

Goldstein

P

,

EUROMAX Investigators

.

Bivalirudin started during emergency transport for primary PCI

.

N Engl J Med

2013

;

369

(

23

):

2207

–

2217

.

204

Schulz

S

,

Richardt

G

,

Laugwitz

KL

,

Morath

T

,

Neudecker

J

,

Hoppmann

P

,

Mehran

R

,

Gershlick

AH

,

Tolg

R

,

Anette Fiedler

K

,

Abdel-Wahab

M

,

Kufner

S

,

Schneider

S

,

Schunkert

H

,

Ibrahim

T

,

Mehilli

J

,

Kastrati

A

,

Bavarian Reperfusion Alternatives Evaluation Investigators

.

Prasugrel plus bivalirudin vs. clopidogrel plus heparin in patients with ST-segment elevation myocardial infarction

.

Eur Heart J

2014

;

35

(

34

):

2285

–

2294

.

205

Shahzad

A

,

Kemp

I

,

Mars

C

,

Wilson

K

,

Roome

C

,

Cooper

R

,

Andron

M

,

Appleby

C

,

Fisher

M

,

Khand

A

,

Kunadian

B

,

Mills

JD

,

Morris

JL

,

Morrison

WL

,

Munir

S

,

Palmer

ND

,

Perry

RA

,

Ramsdale

DR

,

Velavan

P

,

Stables

RH

,

HEAT-PPCI Trial Investigators

.

Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial

.

Lancet

2014

;

384

(

9957

):

1849

–

1858

.

206

Han

Y

,

Guo

J

,

Zheng

Y

,

Zang

H

,

Su

X

,

Wang

Y

,

Chen

S

,

Jiang

T

,

Yang

P

,

Chen

J

,

Jiang

D

,

Jing

Q

,

Liang

Z

,

Liu

H

,

Zhao

X

,

Li

J

,

Li

Y

,

Xu

B

,

Stone

GW

,

BRIGHT Investigators

.

Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: the BRIGHT randomized clinical trial

.

JAMA

2015

;

313

(

13

):

1336

–

1346

.

207

Zeymer

U

,

van 't Hof

A

,

Adgey

J

,

Nibbe

L

,

Clemmensen

P

,

Cavallini

C

,

ten Berg

J

,

Coste

P

,

Huber

K

,

Deliargyris

EN

,

Day

J

,

Bernstein

D

,

Goldstein

P

,

Hamm

C

,

Steg

PG.

Bivalirudin is superior to heparins alone with bailout GP IIb/IIIa inhibitors in patients with ST-segment elevation myocardial infarction transported emergently for primary percutaneous coronary intervention: a pre-specified analysis from the EUROMAX trial

.

Eur Heart J

2014

;

35

(

36

):

2460

–

2467

.

208

Capodanno

D

,

Gargiulo

G

,

Capranzano

P

,

Mehran

R

,

Tamburino

C

,

Stone

GW.

Bivalirudin versus heparin with or without glycoprotein IIb/IIIa inhibitors in patients with STEMI undergoing primary PCI: An updated meta-analysis of 10,350 patients from five randomized clinical trials

.

Eur Heart J Acute Cardiovasc Care

2016

;

5

(

3

):

253

–

262

.

209

Valgimigli

M

,

Frigoli

E

,

Leonardi

S

,

Rothenbuhler

M

,

Gagnor

A

,

Calabro

P

,

Garducci

S

,

Rubartelli

P

,

Briguori

C

,

Ando

G

,

Repetto

A

,

Limbruno

U

,

Garbo

R

,

Sganzerla

P

,

Russo

F

,

Lupi

A

,

Cortese

B

,

Ausiello

A

,

Ierna

S

,

Esposito

G

,

Presbitero

P

,

Santarelli

A

,

Sardella

G

,

Varbella

F

,

Tresoldi

S

,

de Cesare

N

,

Rigattieri

S

,

Zingarelli

A

,

Tosi

P

,

van 't Hof

A

,

Boccuzzi

G

,

Omerovic

E

,

Sabate

M

,

Heg

D

,

Juni

P

,

Vranckx

P

,

MATRIX Investigators

.

Bivalirudin or unfractionated heparin in acute coronary syndromes

.

N Engl J Med

2015

;

373

(

11

):

997

–

1009

.

210

Leonardi

S

,

Frigoli

E

,

Rothenbuhler

M

,

Navarese

E

,

Calabro

P

,

Bellotti

P

,

Briguori

C

,

Ferlini

M

,

Cortese

B

,

Lupi

A

,

Lerna

S

,

Zavallonito-Parenti

D

,

Esposito

G

,

Tresoldi

S

,

Zingarelli

A

,

Rigattieri

S

,

Palmieri

C

,

Liso

A

,

Abate

F

,

Zimarino

M

,

Comeglio

M

,

Gabrielli

G

,

Chieffo

A

,

Brugaletta

S

,

Mauro

C

,

Van Mieghem

NM

,

Heg

D

,

Juni

P

,

Windecker

S

,

Valgimigli

M

,

Investigators

M.

Bivalirudin or unfractionated heparin in patients with acute coronary syndromes managed invasively with and without ST elevation (MATRIX): randomised controlled trial

.

BMJ

2016

;

354

:

i4935

.

211

Kastrati

A

,

Neumann

FJ

,

Mehilli

J

,

Byrne

RA

,

Iijima

R

,

Buttner

HJ

,

Khattab

AA

,

Schulz

S

,

Blankenship

JC

,

Pache

J

,

Minners

J

,

Seyfarth

M

,

Graf

I

,

Skelding

KA

,

Dirschinger

J

,

Richardt

G

,

Berger

PB

,

Schomig

A

,

ISAR-REACT 3 Trial Investigators

.

Bivalirudin versus unfractionated heparin during percutaneous coronary intervention

.

N Engl J Med

2008

;

359

(

7

):

688

–

696

.

212

Ndrepepa

G

,

Schulz

S

,

Keta

D

,

Mehilli

J

,

Birkmeier

A

,

Massberg

S

,

Laugwitz

KL

,

Neumann

FJ

,

Seyfarth

M

,

Berger

PB

,

Schomig

A

,

Kastrati

A.

Bleeding after percutaneous coronary intervention with Bivalirudin or unfractionated Heparin and one-year mortality

.

Am J Cardiol

2010

;

105

(

2

):

163

–

167

.

213

ISIS-2 (Second International Study of Infarct Survival) Collaborative Group

.

Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2

.

Lancet

1988

;

2

(

8607

):

349

–

360

.

214

Patrono

C

,

Andreotti

F

,

Arnesen

H

,

Badimon

L

,

Baigent

C

,

Collet

JP

,

De Caterina

R

,

Gulba

D

,

Huber

K

,

Husted

S

,

Kristensen

SD

,

Morais

J

,

Neumann

FJ

,

Rasmussen

LH

,

Siegbahn

A

,

Steg

PG

,

Storey

RF

,

Van de Werf

F

,

Verheugt

F.

Antiplatelet agents for the treatment and prevention of atherothrombosis

.

Eur Heart J

2011

;

32

(

23

):

2922

–

2932

.

215

Cavender

MA

,

Sabatine

MS.

Bivalirudin versus heparin in patients planned for percutaneous coronary intervention: a meta-analysis of randomised controlled trials

.

Lancet

2014

;

384

(

9943

):

599

–

606

.

216

Stone

GW

,

Selker

HP

,

Thiele

H

,

Patel

MR

,

Udelson

JE

,

Ohman

EM

,

Maehara

A

,

Eitel

I

,

Granger

CB

,

Jenkins

PL

,

Nichols

M

,

Ben-Yehuda

O.

Relationship between infarct size and outcomes following primary PCI: patient-level analysis from 10 randomized trials

.

J Am Coll Cardiol

2016

;

67

(

14

):

1674

–

1683

.

217

Ibanez

B

,

Heusch

G

,

Ovize

M

,

Van de Werf

F.

Evolving therapies for myocardial ischemia/reperfusion injury

.

J Am Coll Cardiol

2015

;

65

(

14

):

1454

–

1471

.

218

Niccoli

G

,

Scalone

G

,

Lerman

A

,

Crea

F.

Coronary microvascular obstruction in acute myocardial infarction

.

Eur Heart J

2016

;

37

(

13

):

1024

–

1033

.

219

Hausenloy

DJ

,

Botker

HE

,

Engstrom

T

,

Erlinge

D

,

Heusch

G

,

Ibanez

B

,

Kloner

RA

,

Ovize

M

,

Yellon

DM

,

Garcia-Dorado

D.

Targeting reperfusion injury in patients with ST-segment elevation myocardial infarction: trials and tribulations

.

Eur Heart J

2017

;

38

(

13

):

935

–

941

.

220

Fibrinolytic Therapy Trialists' (FTT) Collaborative Group

.

Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients

.

Lancet

1994

;

343

(

8893

):

311

–

322

.

221

White

HD.

Thrombolytic therapy in the elderly

.

Lancet

2000

;

356

(

9247

):

2028

–

2030

.

222

Bonnefoy

E

,

Lapostolle

F

,

Leizorovicz

A

,

Steg

G

,

McFadden

EP

,

Dubien

PY

,

Cattan

S

,

Boullenger

E

,

Machecourt

J

,

Lacroute

JM

,

Cassagnes

J

,

Dissait

F

,

Touboul

P

,

Comparison of Angioplasty and Prehospital Thromboysis in Acute Myocardial Infarction Study Group

.

Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study

.

Lancet

2002

;

360

(

9336

):

825

–

829

.

223

Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Investigators

,

Van de Werf

F

,

Adgey

J

,

Ardissino

D

,

Armstrong

PW

,

Aylward

P

,

Barbash

G

,

Betriu

A

,

Binbrek

AS

,

Califf

R

,

Diaz

R

,

Fanebust

R

,

Fox

K

,

Granger

C

,

Heikkila

J

,

Husted

S

,

Jansky

P

,

Langer

A

,

Lupi

E

,

Maseri

A

,

Meyer

J

,

Mlczoch

J

,

Mocceti

D

,

Myburgh

D

,

Oto

A

,

Paolasso

E

,

Pehrsson

K

,

Seabra-Gomes

R

,

Soares-Piegas

L

,

Sugrue

D

,

Tendera

M

,

Topol

E

,

Toutouzas

P

,

Vahanian

A

,

Verheugt

F

,

Wallentin

L

,

White

H.

Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial

.

Lancet

1999

;

354

(

9180

):

716

–

722

.

224

The GUSTO Investigators

.

An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction

.

N Engl J Med

1993

;

329

(

10

):

673

–

682

.

225

Chen

ZM

,

Jiang

LX

,

Chen

YP

,

Xie

JX

,

Pan

HC

,

Peto

R

,

Collins

R

,

Liu

LS

,

COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) Collaborative Group

.

Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial

.

Lancet

2005

;

366

(

9497

):

1607

–

1621

.

226

Sabatine

MS

,

Cannon

CP

,

Gibson

CM

,

Lopez-Sendon

JL

,

Montalescot

G

,

Theroux

P

,

Claeys

MJ

,

Cools

F

,

Hill

KA

,

Skene

AM

,

McCabe

CH

,

Braunwald

E

,

CLARITY-TIMI 28 Investigators

.

Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation

.

N Engl J Med

2005

;

352

(

12

):

1179

–

1189

.

227

Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators

.

Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction

.

Lancet

2001

;

358

(

9282

):

605

–

613

.

228

Wallentin

L

,

Goldstein

P

,

Armstrong

PW

,

Granger

CB

,

Adgey

AAJ

,

Arntz

HR

,

Bogaerts

K

,

Danays

T

,

Lindahl

B

,

Makijarvi

M

,

Verheugt

F

,

Van de Werf

F.

Efficacy and safety of tenecteplase in combination with the low-molecular-weight heparin enoxaparin or unfractionated heparin in the prehospital setting - the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS randomized trial in acute myocardial infarction

.

Circulation

2003

;

108

(

2

):

135

–

142

.

229

Giraldez

RR

,

Nicolau

JC

,

Corbalan

R

,

Gurfinkel

EP

,

Juarez

U

,

Lopez-Sendon

J

,

Parkhomenko

A

,

Molhoek

P

,

Mohanavelu

S

,

Morrow

DA

,

Antman

EM.

Enoxaparin is superior to unfractionated heparin in patients with ST elevation myocardial infarction undergoing fibrinolysis regardless of the choice of lytic: an ExTRACT-TIMI 25 analysis

.

Eur Heart J

2007

;

28

(

13

):

1566

–

1573

.

230

White

HD

,

Braunwald

E

,

Murphy

SA

,

Jacob

AJ

,

Gotcheva

N

,

Polonetsky

L

,

Antman

EM.

Enoxaparin vs. unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction in elderly and younger patients: results from ExTRACT-TIMI 25

.

Eur Heart J

2007

;

28

(

9

):

1066

–

1071

.

231

Ross

AM

,

Molhoek

P

,

Lundergan

C

,

Knudtson

M

,

Draoui

Y

,

Regalado

L

,

Le Louer

V

,

Bigonzi

F

,

Schwartz

W

,

de Jong

E

,

Coyne

K.

Randomized comparison of enoxaparin, a low-molecular-weight heparin, with unfractionated heparin adjunctive to recombinant tissue plasminogen activator thrombolysis and aspirin: second trial of heparin and aspirin reperfusion therapy (HART II)

.

Circulation

2001

;

104

(

6

):

648

–

652

.

232

Antman

EM

,

Louwerenburg

HW

,

Baars

HF

,

Wesdorp

JCL

,

Hamer

B

,

Bassand

JP

,

Bigonzi

F

,

Pisapia

G

,

Gibson

CM

,

Heidbuchel

H

,

Braunwald

E

,

Van de Werf

F.

Enoxaparin as adjunctive antithrombin therapy for ST-elevation myocardial infarction: results of the ENTIRE-thrombolysis in myocardial infarction (TIMI) 23 trial

.

Circulation

2002

;

105

(

14

):

1642

–

1649

.

233

Peters

RJ

,

Joyner

C

,

Bassand

JP

,

Afzal

R

,

Chrolavicius

S

,

Mehta

SR

,

Oldgren

J

,

Wallentin

L

,

Budaj

A

,

Fox

KA

,

Yusuf

S

,

OASIS-6 Investigators

.

The role of fondaparinux as an adjunct to thrombolytic therapy in acute myocardial infarction: a subgroup analysis of the OASIS-6 trial

.

Eur Heart J

2008

;

29

(

3

):

324

–

331

.

234

Fernandez-Aviles

F

,

Alonso

JJ

,

Castro-Beiras

A

,

Vazquez

N

,

Blanco

J

,

Alonso-Briales

J

,

Lopez-Mesa

J

,

Fernandez-Vazquez

F

,

Calvo

I

,

Martinez-Elbal

L

,

San Roman

JA

,

Ramos

B

,

GRACIA (Grupo de Análisis de la Cardiopatía Isquémica Aguda) Group

.

Routine invasive strategy within 24 hours of thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment elevation (GRACIA-1): a randomised controlled trial

.

Lancet

2004

;

364

(

9439

):

1045

–

1053

.

235

Hochman

JS

,

Sleeper

LA

,

White

HD

,

Dzavik

V

,

Wong

SC

,

Menon

V

,

Webb

JG

,

Steingart

R

,

Picard

MH

,

Menegus

MA

,

Boland

J

,

Sanborn

T

,

Buller

CE

,

Modur

S

,

Forman

R

,

Desvigne-Nickens

P

,

Jacobs

AK

,

Slater

JN

,

LeJemtel

TH

,

SHOCK Investigators. One-year survival following early revascularization for cardiogenic shock

.

JAMA

2001

;

285

(

2

):

190

–

192

.

236

Ellis

SG

,

da Silva

ER

,

Heyndrickx

G

,

Talley

JD

,

Cernigliaro

C

,

Steg

G

,

Spaulding

C

,

Nobuyoshi

M

,

Erbel

R

,

Vassanelli

C

,

Topol

EJ

,

RESCUE Investigators

.

Randomized comparison of rescue angioplasty with conservative management of patients with early failure of thrombolysis for acute anterior myocardial infarction

.

Circulation

1994

;

90

(

5

):

2280

–

2284

.

237

Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT-4 PCI) Investigators

.

Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial

.

Lancet

2006

;

367

(

9510

):

569

–

578

.

238

Sinnaeve

PR

,

Armstrong

PW

,

Gershlick

AH

,

Goldstein

P

,

Wilcox

R

,

Lambert

Y

,

Danays

T

,

Soulat

L

,

Halvorsen

S

,

Ortiz

FR

,

Vandenberghe

K

,

Regelin

A

,

Bluhmki

E

,

Bogaerts

K

,

Van de Werf

F

,

STREAM Investigators

.

ST-segment-elevation myocardial infarction patients randomized to a pharmaco-invasive strategy or primary percutaneous coronary intervention: Strategic Reperfusion Early After Myocardial Infarction (STREAM) 1-year mortality follow-up

.

Circulation

2014

;

130

(

14

):

1139

–

1145

.

239

Scheller

B

,

Hennen

B

,

Hammer

B

,

Walle

J

,

Hofer

C

,

Hilpert

V

,

Winter

H

,

Nickenig

G

,

Bohm

M

,

SIAM III Study Group

.

Beneficial effects of immediate stenting after thrombolysis in acute myocardial infarction

.

J Am Coll Cardiol

2003

;

42

(

4

):

634

–

641

.

240

Le May

MR

,

Wells

GA

,

Labinaz

M

,

Davies

RF

,

Turek

M

,

Leddy

D

,

Maloney

J

,

McKibbin

T

,

Quinn

B

,

Beanlands

RS

,

Glover

C

,

Marquis

JF

,

O'Brien

ER

,

Williams

WL

,

Higginson

LA.

Combined angioplasty and pharmacological intervention versus thrombolysis alone in acute myocardial infarction (CAPITAL AMI study)

.

J Am Coll Cardiol

2005

;

46

(

3

):

417

–

424

.

241

Abdel-Qadir

H

,

Yan

AT

,

Tan

M

,

Borgia

F

,

Piscione

F

,

Di Mario

C

,

Halvorsen

S

,

Cantor

WJ

,

Westerhout

CM

,

Scheller

B

,

Le May

MR

,

Fernandez-Aviles

F

,

Sanchez

PL

,

Lee

DS

,

Goodman

SG.

Consistency of benefit from an early invasive strategy after fibrinolysis: a patient-level meta-analysis

.

Heart

2015

;

101

(

19

):

1554

–

1561

.

242

Sanchez

PL

,

Gimeno

F

,

Ancillo

P

,

Sanz

JJ

,

Alonso-Briales

JH

,

Bosa

F

,

Santos

I

,

Sanchis

J

,

Bethencourt

A

,

Lopez-Messa

J

,

de Prado

AP

,

Alonso

JJ

,

San Roman

JA

,

Fernandez-Aviles

F.

Role of the paclitaxel-eluting stent and tirofiban in patients with ST-elevation myocardial infarction undergoing postfibrinolysis angioplasty: the GRACIA-3 randomized clinical trial

.

Circ Cardiovasc Interv

2010

;

3

(

4

):

297

–

307

.

243

White

HD

,

Hirulog and Early Reperfusion or Occlusion (HERO)-2 Trial Investigators

.

Thrombin-specific anticoagulation with bivalirudin versus heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: the HERO-2 randomised trial

.

Lancet

2001

;

358

(

9296

):

1855

–

1863

.

244

Fernandez-Aviles

F

,

Alonso

JJ

,

Pena

G

,

Blanco

J

,

Alonso-Briales

J

,

Lopez-Mesa

J

,

Fernandez-Vazquez

F

,

Moreu

J

,

Hernandez

RA

,

Castro-Beiras

A

,

Gabriel

R

,

Gibson

CM

,

Sanchez

PL

,

GRACIA-2 (Groupo de Análisis de Cardiopatía Isquémica Aguda) Investigators

.

Primary angioplasty vs. early routine post-fibrinolysis angioplasty for acute myocardial infarction with ST-segment elevation: the GRACIA-2 non-inferiority, randomized, controlled trial

.

Eur Heart J

2007

;

28

(

8

):

949

–

960

.

245

Van de Werf

F

,

Barron

HV

,

Armstrong

PW

,

Granger

CB

,

Berioli

S

,

Barbash

G

,

Pehrsson

K

,

Verheugt

FW

,

Meyer

J

,

Betriu

A

,

Califf

RM

,

Li

X

,

Fox

NL

,

ASSENT-2 Investigators, Assessment of the safety and efficacy of a new thrombolytic

.

Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents: a comparison of TNK-tPA and rt-PA

.

Eur Heart J

2001

;

22

(

24

):

2253

–

2261

.

246

The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) Investigators

.

A comparison of reteplase with alteplase for acute myocardial infarction

.

N Engl J Med

1997

;

337

(

16

):

1118

–

1123

.

247

Bottiger

BW

,

Arntz

HR

,

Chamberlain

DA

,

Bluhmki

E

,

Belmans

A

,

Danays

T

,

Carli

PA

,

Adgey

JA

,

Bode

C

,

Wenzel

V

,

TROICA Trial Investigators

,

European Resuscitation Council Study Group

.

Thrombolysis during resuscitation for out-of-hospital cardiac arrest

.

N Engl J Med

2008

;

359

(

25

):

2651

–

2662

.

248

Hochman

JS

,

Sleeper

LA

,

Webb

JG

,

Sanborn

TA

,

White

HD

,

Talley

JD

,

Buller

CE

,

Jacobs

AK

,

Slater

JN

,

Col

J

,

McKinlay

SM

,

LeJemtel

TH.

Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock

.

N Engl J Med

1999

;

341

(

9

):

625

–

634

.

249

Weiss

ES

,

Chang

DD

,

Joyce

DL

,

Nwakanma

LU

,

Yuh

DD.

Optimal timing of coronary artery bypass after acute myocardial infarction: a review of California discharge data

.

J Thorac Cardiovasc Surg

2008

;

135

(

3

):

503

–

511

.

250

Hansson

EC

,

Jideus

L

,

Aberg

B

,

Bjursten

H

,

Dreifaldt

M

,

Holmgren

A

,

Ivert

T

,

Nozohoor

S

,

Barbu

M

,

Svedjeholm

R

,

Jeppsson

A.

Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel: a nationwide study

.

Eur Heart J

2016

;

37

(

2

):

189

–

197

.

251

Deja

MA

,

Kargul

T

,

Domaradzki

W

,

Stacel

T

,

Mazur

W

,

Wojakowski

W

,

Gocol

R

,

Gaszewska-Zurek

E

,

Zurek

P

,

Pytel

A

,

Wos

S.

Effects of preoperative aspirin in coronary artery bypass grafting: a double-blind, placebo-controlled, randomized trial

.

J Thorac Cardiovasc Surg

2012

;

144

(

1

):

204

–

209

.

252

Lim

E

,

Ali

Z

,

Ali

A

,

Routledge

T

,

Edmonds

L

,

Altman

DG

,

Large

S.

Indirect comparison meta-analysis of aspirin therapy after coronary surgery

.

BMJ

2003

;

327

(

7427

):

1309

.

253

Gavaghan

TP

,

Gebski

V

,

Baron

DW.

Immediate postoperative aspirin improves vein graft patency early and late after coronary artery bypass graft surgery. A placebo-controlled, randomized study

.

Circulation

1991

;

83

(

5

):

1526

–

1533

.

254

Hasin

Y

,

Danchin

N

,

Filippatos

GS

,

Heras

M

,

Janssens

U

,

Leor

J

,

Nahir

M

,

Parkhomenko

A

,

Thygesen

K

,

Tubaro

M

,

Wallentin

LC

,

Zakke

I.

Recommendations for the structure, organization, and operation of intensive cardiac care units

.

Eur Heart J

2005

;

26

(

16

):

1676

–

1682

.

255

Spencer

FA

,

Lessard

D

,

Gore

JM

,

Yarzebski

J

,

Goldberg

RJ.

Declining length of hospital stay for acute myocardial infarction and postdischarge outcomes: a community-wide perspective

.

Arch Intern Med

2004

;

164

(

7

):

733

–

740

.

256

Berger

AK

,

Duval

S

,

Jacobs

DR

Jr,

Barber

C

,

Vazquez

G

,

Lee

S

,

Luepker

RV.

Relation of length of hospital stay in acute myocardial infarction to postdischarge mortality

.

Am J Cardiol

2008

;

101

(

4

):

428

–

434

.

257

Grines

CL

,

Marsalese

DL

,

Brodie

B

,

Griffin

J

,

Donohue

B

,

Costantini

CR

,

Balestrini

C

,

Stone

G

,

Wharton

T

,

Esente

P

,

Spain

M

,

Moses

J

,

Nobuyoshi

M

,

Ayres

M

,

Jones

D

,

Mason

D

,

Sachs

D

,

Grines

LL

,

O'Neill

W.

Safety and cost-effectiveness of early discharge after primary angioplasty in low risk patients with acute myocardial infarction. PAMI-II Investigators. Primary Angioplasty in Myocardial Infarction

.

J Am Coll Cardiol

1998

;

31

(

5

):

967

–

972

.

258

De Luca

G

,

Suryapranata

H

,

van 't Hof

AW

,

de Boer

MJ

,

Hoorntje

JC

,

Dambrink

JH

,

Gosselink

AT

,

Ottervanger

JP

,

Zijlstra

F.

Prognostic assessment of patients with acute myocardial infarction treated with primary angioplasty: implications for early discharge

.

Circulation

2004

;

109

(

22

):

2737

–

2743

.

259

Azzalini

L

,

Sole

E

,

Sans

J

,

Vila

M

,

Duran

A

,

Gil-Alonso

D

,

Santalo

M

,

Garcia-Moll

X

,

Sionis

A.

Feasibility and safety of an early discharge strategy after low-risk acute myocardial infarction treated with primary percutaneous coronary intervention: the EDAMI pilot trial

.

Cardiology

2015

;

130

(

2

):

120

–

129

.

260

Melberg

T

,

Jorgensen

M

,

Orn

S

,

Solli

T

,

Edland

U

,

Dickstein

K.

Safety and health status following early discharge in patients with acute myocardial infarction treated with primary PCI: a randomized trial

.

Eur J Prev Cardiol

2015

;

22

(

11

):

1427

–

1434

.

261

Noman

A

,

Zaman

AG

,

Schechter

C

,

Balasubramaniam

K

,

Das

R.

Early discharge after primary percutaneous coronary intervention for ST-elevation myocardial infarction

.

Eur Heart J Acute Cardiovasc Care

2013

;

2

(

3

):

262

–

269

.

262

Jones

DA

,

Rathod

KS

,

Howard

JP

,

Gallagher

S

,

Antoniou

S

,

De Palma

R

,

Guttmann

O

,

Cliffe

S

,

Colley

J

,

Butler

J

,

Ferguson

E

,

Mohiddin

S

,

Kapur

A

,

Knight

CJ

,

Jain

AK

,

Rothman

MT

,

Mathur

A

,

Timmis

AD

,

Smith

EJ

,

Wragg

A.

Safety and feasibility of hospital discharge 2 days following primary percutaneous intervention for ST-segment elevation myocardial infarction

.

Heart

2012

;

98

(

23

):

1722

–

1727

.

263

Estevez-Loureiro

R

,

Calvino-Santos

R

,

Vazquez

JM

,

Barge-Caballero

E

,

Salgado-Fernandez

J

,

Pineiro

M

,

Freire-Tellado

M

,

Varela-Portas

J

,

Martinez

L

,

Gomez

S

,

Rodriguez

JA

,

Vazquez

N

,

Castro-Beiras

A.

Safety and feasibility of returning patients early to their originating centers after transfer for primary percutaneous coronary intervention

.

Rev Esp Cardiol

2009

;

62

(

12

):

1356

–

1364

.

264

Morrow

DA

,

Antman

EM

,

Charlesworth

A

,

Cairns

R

,

Murphy

SA

,

de Lemos

JA

,

Giugliano

RP

,

McCabe

CH

,

Braunwald

E.

TIMI risk score for ST-elevation myocardial infarction: A convenient, bedside, clinical score for risk assessment at presentation: An intravenous nPA for treatment of infarcting myocardium early II trial substudy

.

Circulation

2000

;

102

(

17

):

2031

–

2037

.

265

Newby

LK

,

Hasselblad

V

,

Armstrong

PW

,

Van de

Werf F

,

Mark

DB

,

White

HD

,

Topol

EJ

,

Califf

RM.

Time-based risk assessment after myocardial infarction. Implications for timing of discharge and applications to medical decision-making

.

Eur Heart J

2003

;

24

(

2

):

182

–

189

.

266

Dans

AL

,

Connolly

SJ

,

Wallentin

L

,

Yang

S

,

Nakamya

J

,

Brueckmann

M

,

Ezekowitz

M

,

Oldgren

J

,

Eikelboom

JW

,

Reilly

PA

,

Yusuf

S.

Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial

.

Circulation

2013

;

127

(

5

):

634

–

640

.

267

Sorensen

R

,

Hansen

ML

,

Abildstrom

SZ

,

Hvelplund

A

,

Andersson

C

,

Jorgensen

C

,

Madsen

JK

,

Hansen

PR

,

Kober

L

,

Torp-Pedersen

C

,

Gislason

GH.

Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data

.

Lancet

2009

;

374

(

9706

):

1967

–

1974

.

268

Hansen

ML

,

Sorensen

R

,

Clausen

MT

,

Fog-Petersen

ML

,

Raunso

J

,

Gadsboll

N

,

Gislason

GH

,

Folke

F

,

Andersen

SS

,

Schramm

TK

,

Abildstrom

SZ

,

Poulsen

HE

,

Kober

L

,

Torp-Pedersen

C.

Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation

.

Arch Intern Med

2010

;

170

(

16

):

1433

–

1441

.

269

Oldgren

J

,

Budaj

A

,

Granger

CB

,

Khder

Y

,

Roberts

J

,

Siegbahn

A

,

Tijssen

JG

,

Van de Werf

F

,

Wallentin

L

,

Investigators R-D

.

Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial

.

Eur Heart J

2011

;

32

(

22

):

2781

–

2789

.

270

Barnes

GD

,

Gu

X

,

Haymart

B

,

Kline-Rogers

E

,

Almany

S

,

Kozlowski

J

,

Besley

D

,

Krol

GD

,

Froehlich

JB

,

Kaatz

S.

The predictive ability of the CHADS2 and CHA2DS2-VASc scores for bleeding risk in atrial fibrillation: the MAQI(2) experience

.

Thromb Res

2014

;

134

(

2

):

294

–

299

.

271

Roldan

V

,

Marin

F

,

Manzano-Fernandez

S

,

Gallego

P

,

Vilchez

JA

,

Valdes

M

,

Vicente

V

,

Lip

GY.

The HAS-BLED score has better prediction accuracy for major bleeding than CHADS2 or CHA2DS2-VASc scores in anticoagulated patients with atrial fibrillation

.

J Am Coll Cardiol

2013

;

62

(

23

):

2199

–

2204

.

272

Gibson

CM

,

Mehran

R

,

Bode

C

,

Halperin

J

,

Verheugt

FW

,

Wildgoose

P

,

Birmingham

M

,

Ianus

J

,

Burton

P

,

van Eickels

M

,

Korjian

S

,

Daaboul

Y

,

Lip

GY

,

Cohen

M

,

Husted

S

,

Peterson

ED

,

Fox

KA.

Prevention of bleeding in patients with atrial fibrillation undergoing PCI

.

N Engl J Med

2016

;

375

(

25

):

2423

–

2434

.

273

Toleva

O

,

Ibrahim

Q

,

Brass

N

,

Sookram

S

,

Welsh

R.

Treatment choices in elderly patients with ST: elevation myocardial infarction-insights from the Vital Heart Response registry

.

Open Heart

2015

;

2

(

1

):

e000235

.

274

Malkin

CJ

,

Prakash

R

,

Chew

DP.

The impact of increased age on outcome from a strategy of early invasive management and revascularisation in patients with acute coronary syndromes: retrospective analysis study from the ACACIA registry

.

BMJ Open

2012

;

2

(

1

):

e000540

.

275

Alexander

KP

,

Chen

AY

,

Roe

MT

,

Newby

LK

,

Gibson

CM

,

Allen-LaPointe

NM

,

Pollack

C

,

Gibler

WB

,

Ohman

EM

,

Peterson

ED

,

CRUSADE Investigators

.

Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes

.

JAMA

2005

;

294

(

24

):

3108

–

3116

.

276

Bueno

H

,

Betriu

A

,

Heras

M

,

Alonso

JJ

,

Cequier

A

,

Garcia

EJ

,

Lopez-Sendon

JL

,

Macaya

C

,

Hernandez-Antolin

R

,

TRIANA Investigators

.

Primary angioplasty vs. fibrinolysis in very old patients with acute myocardial infarction: TRIANA (TRatamiento del Infarto Agudo de miocardio eN Ancianos) randomized trial and pooled analysis with previous studies

.

Eur Heart J

2011

;

32

(

1

):

51

–

60

.

277

Szummer

K

,

Lundman

P

,

Jacobson

SH

,

Schon

S

,

Lindback

J

,

Stenestrand

U

,

Wallentin

L

,

Jernberg

T

,

SWEDEHEART

.

Relation between renal function, presentation, use of therapies and in-hospital complications in acute coronary syndrome: data from the SWEDEHEART register

.

J Intern Med

2010

;

268

(

1

):

40

–

49

.

278

Timmer

JR

,

Ottervanger

JP

,

de Boer

MJ

,

Boersma

E

,

Grines

CL

,

Westerhout

CM

,

Simes

RJ

,

Granger

CB

,

Zijlstra

F

,

Primary Coronary Angioplasty vs Thrombolysis-2 Trialists Collaborators Group

.

Primary percutaneous coronary intervention compared with fibrinolysis for myocardial infarction in diabetes mellitus: results from the Primary Coronary Angioplasty vs Thrombolysis-2 trial

.

Arch Intern Med

2007

;

167

(

13

):

1353

–

1359

.

279

Alderman

EL

,

Kip

KE

,

Whitlow

PL

,

Bashore

T

,

Fortin

D

,

Bourassa

MG

,

Lesperance

J

,

Schwartz

L

,

Stadius

M

,

Bypass Angioplasty Revascularization Investigation

.

Native coronary disease progression exceeds failed revascularization as cause of angina after five years in the Bypass Angioplasty Revascularization Investigation (BARI)

.

J Am Coll Cardiol

2004

;

44

(

4

):

766

–

774

.

280

James

S

,

Angiolillo

DJ

,

Cornel

JH

,

Erlinge

D

,

Husted

S

,

Kontny

F

,

Maya

J

,

Nicolau

JC

,

Spinar

J

,

Storey

RF

,

Stevens

SR

,

Wallentin

L

,

PLATO Study Group

.

Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO) trial

.

Eur Heart J

2010

;

31

(

24

):

3006

–

3016

.

281

NICE-SUGAR Study Investigators

,

Finfer

S

,

Chittock

DR

,

Su

SY

,

Blair

D

,

Foster

D

,

Dhingra

V

,

Bellomo

R

,

Cook

D

,

Dodek

P

,

Henderson

WR

,

Hebert

PC

,

Heritier

S

,

Heyland

DK

,

McArthur

C

,

McDonald

E

,

Mitchell

I

,

Myburgh

JA

,

Norton

R

,

Potter

J

,

Robinson

BG

,

Ronco

JJ.

Intensive versus conventional glucose control in critically ill patients

.

N Engl J Med

2009

;

360

(

13

):

1283

–

1297

.

282

Senthinathan

A

,

Kelly

V

,

Dzingina

M

,

Jones

D

,

Baker

M

,

Longson

D

,

Guideline Development Group

.

Hyperglycaemia in acute coronary syndromes: summary of NICE guidance

.

BMJ

2011

;

343

:

d6646

.

283

Fox

KA

,

Dabbous

OH

,

Goldberg

RJ

,

Pieper

KS

,

Eagle

KA

,

Van de Werf

F

,

Avezum

A

,

Goodman

SG

,

Flather

MD

,

Anderson

FA

Jr,

Granger

CB.

Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE)

.

BMJ

2006

;

333

(

7578

):

1091

.

284

Fox

KA

,

Fitzgerald

G

,

Puymirat

E

,

Huang

W

,

Carruthers

K

,

Simon

T

,

Coste

P

,

Monsegu

J

,

Gabriel Steg

P

,

Danchin

N

,

Anderson

F.

Should patients with acute coronary disease be stratified for management according to their risk? Derivation, external validation and outcomes using the updated GRACE risk score

.

BMJ Open

2014

;

4

(

2

):

e004425

.

285

van Loon

RB

,

Veen

G

,

Baur

LH

,

Kamp

O

,

Bronzwaer

JG

,

Twisk

JW

,

Verheugt

FW

,

van Rossum

AC.

Improved clinical outcome after invasive management of patients with recent myocardial infarction and proven myocardial viability: primary results of a randomized controlled trial (VIAMI-trial)

.

Trials

2012

;

13

:

1

.

286

van Loon

RB

,

Veen

G

,

Baur

LH

,

Twisk

JW

,

van Rossum

AC.

Long-term follow-up of the viability guided angioplasty after acute myocardial infarction (VIAMI) trial

.

Int J Cardiol

2015

;

186

:

111

–

116

.

287

Neskovic

AN

,

Bojic

M

,

Popovic

AD.

Detection of significant residual stenosis of the infarct-related artery after thrombolysis by high-dose dipyridamole echocardiography test: is it detected often enough?

Clin Cardiol

1997

;

20

(

6

):

569

–

572

.

288

Kim

RJ

,

Wu

E

,

Rafael

A

,

Chen

EL

,

Parker

MA

,

Simonetti

O

,

Klocke

FJ

,

Bonow

RO

,

Judd

RM.

The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction

.

N Engl J Med

2000

;

343

(

20

):

1445

–

1453

.

289

La Canna

G

,

Rahimtoola

SH

,

Visioli

O

,

Giubbini

R

,

Alfieri

O

,

Zognio

M

,

Milan

E

,

Ceconi

C

,

Gargano

M

,

Lo Russo

R

,

Ferrari

R.

Sensitivity, specificity, and predictive accuracies of non-invasive tests, singly and in combination, for diagnosis of hibernating myocardium

.

Eur Heart J

2000

;

21

(

16

):

1358

–

1367

.

290

Gerber

BL

,

Rousseau

MF

,

Ahn

SA

,

le Polain de Waroux

JB

,

Pouleur

AC

,

Phlips

T

,

Vancraeynest

D

,

Pasquet

A

,

Vanoverschelde

JL.

Prognostic value of myocardial viability by delayed-enhanced magnetic resonance in patients with coronary artery disease and low ejection fraction: impact of revascularization therapy

.

J Am Coll Cardiol

2012

;

59

(

9

):

825

–

835

.

291

Shah

DJ

,

Kim

HW

,

James

O

,

Parker

M

,

Wu

E

,

Bonow

RO

,

Judd

RM

,

Kim

RJ.

Prevalence of regional myocardial thinning and relationship with myocardial scarring in patients with coronary artery disease

.

JAMA

2013

;

309

(

9

):

909

–

918

.

292

Beanlands

RS

,

Nichol

G

,

Huszti

E

,

Humen

D

,

Racine

N

,

Freeman

M

,

Gulenchyn

KY

,

Garrard

L

,

deKemp

R

,

Guo

A

,

Ruddy

TD

,

Benard

F

,

Lamy

A

,

Iwanochko

RM

,

PARR-2 Investigators

.

F-18-fluorodeoxyglucose positron emission tomography imaging-assisted management of patients with severe left ventricular dysfunction and suspected coronary disease: a randomized, controlled trial (PARR-2)

.

J Am Coll Cardiol

2007

;

50

(

20

):

2002

–

2012

.

293

Allman

KC

,

Shaw

LJ

,

Hachamovitch

R

,

Udelson

JE.

Myocardial viability testing and impact of revascularization on prognosis in patients with coronary artery disease and left ventricular dysfunction: a meta-analysis

.

J Am Coll Cardiol

2002

;

39

(

7

):

1151

–

1158

.

294

Eitel

I

,

de Waha

S

,

Wohrle

J

,

Fuernau

G

,

Lurz

P

,

Pauschinger

M

,

Desch

S

,

Schuler

G

,

Thiele

H.

Comprehensive prognosis assessment by CMR imaging after ST-segment elevation myocardial infarction

.

J Am Coll Cardiol

2014

;

64

(

12

):

1217

–

1226

.

295

Neskovic

AN

,

Hagendorff

A

,

Lancellotti

P

,

Guarracino

F

,

Varga

A

,

Cosyns

B

,

Flachskampf

FA

,

Popescu

BA

,

Gargani

L

,

Zamorano

JL

,

Badano

LP

,

European Association of Cardiovascular Imaging

.

Emergency echocardiography: the European Association of Cardiovascular Imaging recommendations

.

Eur Heart J Cardiovasc Imaging

2013

;

14

(

1

):

1

–

11

.

296

Soholm

H

,

Lonborg

J

,

Andersen

MJ

,

Vejlstrup

N

,

Engstrom

T

,

Moller

JE

,

Hassager

C.

Repeated echocardiography after first ever ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention – is it necessary?

Eur Heart J Acute Cardiovasc Care

2015

;

4

(

6

):

528

–

536

.

297

St John Sutton

M

,

Pfeffer

MA

,

Plappert

T

,

Rouleau

JL

,

Moye

LA

,

Dagenais

GR

,

Lamas

GA

,

Klein

M

,

Sussex

B

,

Goldman

S

,

Menapace

FJ

Jr,

Parker

JO

,

Lewis

S

,

Sestier

F

,

Gordon

DF

,

McEwan

P

,

Bernstein

V

,

Braunwald

E

,

SAVE Investigators

.

Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril

.

Circulation

1994

;

89

(

1

):

68

–

75

.

298

Carlos

ME

,

Smart

SC

,

Wynsen

JC

,

Sagar

KB.

Dobutamine stress echocardiography for risk stratification after myocardial infarction

.

Circulation

1997

;

95

(

6

):

1402

–

1410

.

299

Brown

KA

,

Heller

GV

,

Landin

RS

,

Shaw

LJ

,

Beller

GA

,

Pasquale

MJ

,

Haber

SB.

Early dipyridamole (99m)Tc-sestamibi single photon emission computed tomographic imaging 2 to 4 days after acute myocardial infarction predicts in-hospital and postdischarge cardiac events: comparison with submaximal exercise imaging

.

Circulation

1999

;

100

(

20

):

2060

–

2066

.

300

Bulluck

H

,

White

SK

,

Frohlich

GM

,

Casson

SG

,

O'Meara

C

,

Newton

A

,

Nicholas

J

,

Weale

P

,

Wan

SM

,

Sirker

A

,

Moon

JC

,

Yellon

DM

,

Groves

A

,

Menezes

L

,

Hausenloy

DJ.

Quantifying the area at risk in reperfused ST-segment-elevation myocardial infarction patients using hybrid cardiac positron emission tomography-magnetic resonance imaging

.

Circ Cardiovasc Imaging

2016

;

9

(

3

):

e003900

.

301

Chow

CK

,

Jolly

S

,

Rao-Melacini

P

,

Fox

KA

,

Anand

SS

,

Yusuf

S.

Association of diet, exercise, and smoking modification with risk of early cardiovascular events after acute coronary syndromes

.

Circulation

2010

;

121

(

6

):

750

–

758

.

302

Thomson

CC

,

Rigotti

NA.

Hospital- and clinic-based smoking cessation interventions for smokers with cardiovascular disease

.

Prog Cardiovasc Dis

2003

;

45

(

6

):

459

–

479

.

303

Rigotti

NA

,

Clair

C

,

Munafo

MR

,

Stead

LF.

Interventions for smoking cessation in hospitalised patients

.

Cochrane Database Syst Rev

2012

;

5

:

CD001837

.

304

Critchley

JA

,

Capewell

S.

Mortality risk reduction associated with smoking cessation in patients with coronary heart disease: a systematic review

.

JAMA

2003

;

290

(

1

):

86

–

97

.

305

Rallidis

LS

,

Pavlakis

G.

The fundamental importance of smoking cessation in those with premature ST-segment elevation acute myocardial infarction

.

Curr Opin Cardiol

2016

;

31

(

5

):

531

–

536

.

306

Stead

LF

,

Koilpillai

P

,

Fanshawe

TR

,

Lancaster

T.

Combined pharmacotherapy and behavioural interventions for smoking cessation

.

Cochrane Database Syst Rev

2016

;

3

:

CD008286

.

307

McRobbie

H

,

Bullen

C

,

Hartmann-Boyce

J

,

Hajek

P.

Electronic cigarettes for smoking cessation and reduction

.

Cochrane Database Syst Rev

2014

;

12

:

CD010216

.

308

Global BMI Mortality Collaboration

,

Di Angelantonio

E

,

Bhupathiraju Sh

N

,

Wormser

D

,

Gao

P

,

Kaptoge

S

,

Berrington de Gonzalez

A

,

Cairns

BJ

,

Huxley

R

,

Jackson Ch

L

,

Joshy

G

,

Lewington

S

,

Manson

JE

,

Murphy

N

,

Patel

AV

,

Samet

JM

,

Woodward

M

,

Zheng

W

,

Zhou

M

,

Bansal

N

,

Barricarte

A

,

Carter

B

,

Cerhan

JR

,

Smith

GD

,

Fang

X

,

Franco

OH

,

Green

J

,

Halsey

J

,

Hildebrand

JS

,

Jung

KJ

,

Korda

RJ

,

McLerran

DF

,

Moore

SC

,

O'Keeffe

LM

,

Paige

E

,

Ramond

A

,

Reeves

GK

,

Rolland

B

,

Sacerdote

C

,

Sattar

N

,

Sofianopoulou

E

,

Stevens

J

,

Thun

M

,

Ueshima

H

,

Yang

L

,

Yun

YD

,

Willeit

P

,

Banks

E

,

Beral

V

,

Chen

Z

,

Gapstur

SM

,

Gunter

MJ

,

Hartge

P

,

Jee

SH

,

Lam

TH

,

Peto

R

,

Potter

JD

,

Willett

WC

,

Thompson

SG

,

Danesh

J

,

Hu

FB.

Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents

.

Lancet

2016

;

388

(

10046

):

776

–

786

.

309

Anderson

L

,

Oldridge

N

,

Thompson

DR

,

Zwisler

AD

,

Rees

K

,

Martin

N

,

Taylor

RS.

Exercise-based cardiac rehabilitation for coronary heart disease: Cochrane systematic review and meta-analysis

.

J Am Coll Cardiol

2016

;

67

(

1

):

1

–

12

.

310

Taylor

RS

,

Brown

A

,

Ebrahim

S

,

Jolliffe

J

,

Noorani

H

,

Rees

K

,

Skidmore

B

,

Stone

JA

,

Thompson

DR

,

Oldridge

N.

Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials

.

Am J Med

2004

;

116

(

10

):

682

–

692

.

311

Dalal

HM

,

Zawada

A

,

Jolly

K

,

Moxham

T

,

Taylor

RS.

Home based versus centre based cardiac rehabilitation: Cochrane systematic review and meta-analysis

.

BMJ

2010

;

340

:

b5631

.

312

European Association of Cardiovascular Prevention and Rehabilitation Committee for Science Guidelines, EACPR

,

Corra

U

,

Piepoli

MF

,

Carre

F

,

Heuschmann

P

,

Hoffmann

U

,

Verschuren

M

,

Halcox

J

,

Document

R

,

Giannuzzi

P

,

Saner

H

,

Wood

D

,

Piepoli

MF

,

Corra

U

,

Benzer

W

,

Bjarnason-Wehrens

B

,

Dendale

P

,

Gaita

D

,

McGee

H

,

Mendes

M

,

Niebauer

J

,

Zwisler

AD

,

Schmid

JP.

Secondary prevention through cardiac rehabilitation: physical activity counselling and exercise training: key components of the position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation

.

Eur Heart J

2010

;

31

(

16

):

1967

–

1974

.

313

Dreyer

RP

,

Xu

X

,

Zhang

W

,

Du

X

,

Strait

KM

,

Bierlein

M

,

Bucholz

EM

,

Geda

M

,

Fox

J

,

D'Onofrio

G

,

Lichtman

JH

,

Bueno

H

,

Spertus

JA

,

Krumholz

HM.

Return to work after acute myocardial infarction: comparison between young women and men

.

Circ Cardiovasc Qual Outcomes

2016

;

9

(2 Suppl 1)

:

S45

–

S52

.

314

Smith

D

,

Toff

W

,

Joy

M

,

Dowdall

N

,

Johnston

R

,

Clark

L

,

Gibbs

S

,

Boon

N

,

Hackett

D

,

Aps

C

,

Anderson

M

,

Cleland

J.

Fitness to fly for passengers with cardiovascular disease

.

Heart

2010

;

96

(Suppl 2)

:

ii1

–

ii16

.

315

SPRINT Research Group

,

Wright

JT

Jr,

Williamson

JD

,

Whelton

PK

,

Snyder

JK

,

Sink

KM

,

Rocco

MV

,

Reboussin

DM

,

Rahman

M

,

Oparil

S

,

Lewis

CE

,

Kimmel

PL

,

Johnson

KC

,

Goff

DC

Jr,

Fine

LJ

,

Cutler

JA

,

Cushman

WC

,

Cheung

AK

,

Ambrosius

WT.

A randomized trial of intensive versus standard blood-pressure control

.

N Engl J Med

2015

;

373

(

22

):

2103

–

2116

.

316

Lonn

EM

,

Bosch

J

,

Lopez-Jaramillo

P

,

Zhu

J

,

Liu

L

,

Pais

P

,

Diaz

R

,

Xavier

D

,

Sliwa

K

,

Dans

A

,

Avezum

A

,

Piegas

LS

,

Keltai

K

,

Keltai

M

,

Chazova

I

,

Peters

RJ

,

Held

C

,

Yusoff

K

,

Lewis

BS

,

Jansky

P

,

Parkhomenko

A

,

Khunti

K

,

Toff

WD

,

Reid

CM

,

Varigos

J

,

Leiter

LA

,

Molina

DI

,

McKelvie

R

,

Pogue

J

,

Wilkinson

J

,

Jung

H

,

Dagenais

G

,

Yusuf

S

,

HOPE-3 Investigators

.

Blood-pressure lowering in intermediate-risk persons without cardiovascular disease

.

N Engl J Med

2016

;

374

(

21

):

2009

–

2020

.

317

Simpson

SH

,

Eurich

DT

,

Majumdar

SR

,

Padwal

RS

,

Tsuyuki

RT

,

Varney

J

,

Johnson

JA.

A meta-analysis of the association between adherence to drug therapy and mortality

.

BMJ

2006

;

333

(

7557

):

15

.

318

Faridi

KF

,

Peterson

ED

,

McCoy

LA

,

Thomas

L

,

Enriquez

J

,

Wang

TY.

Timing of first postdischarge follow-up and medication adherence after acute myocardial infarction

.

JAMA Cardiol

2016

;

1

(

2

):

147

–

155

.

319

Naderi

SH

,

Bestwick

JP

,

Wald

DS.

Adherence to drugs that prevent cardiovascular disease: meta-analysis on 376,162 patients

.

Am J Med

2012

;

125

(

9

):

882

–

887 e1

.

320

Marcum

ZA

,

Sevick

MA

,

Handler

SM.

Medication nonadherence: a diagnosable and treatable medical condition

.

JAMA

2013

;

309

(

20

):

2105

–

2106

.

321

Castellano

JM

,

Sanz

G

,

Fernandez Ortiz

A

,

Garrido

E

,

Bansilal

S

,

Fuster

V.

A polypill strategy to improve global secondary cardiovascular prevention: from concept to reality

.

J Am Coll Cardiol

2014

;

64

(

6

):

613

–

621

.

322

Thom

S

,

Poulter

N

,

Field

J

,

Patel

A

,

Prabhakaran

D

,

Stanton

A

,

Grobbee

DE

,

Bots

ML

,

Reddy

KS

,

Cidambi

R

,

Bompoint

S

,

Billot

L

,

Rodgers

A

,

UMPIRE Collaborative Group

.

Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial

.

JAMA

2013

;

310

(

9

):

918

–

929

.

323

Castellano

JM

,

Sanz

G

,

Penalvo

JL

,

Bansilal

S

,

Fernandez-Ortiz

A

,

Alvarez

L

,

Guzman

L

,

Linares

JC

,

Garcia

F

,

D'Aniello

F

,

Arnaiz

JA

,

Varea

S

,

Martinez

F

,

Lorenzatti

A

,

Imaz

I

,

Sanchez-Gomez

LM

,

Roncaglioni

MC

,

Baviera

M

,

Smith

SC

Jr,

Taubert

K

,

Pocock

S

,

Brotons

C

,

Farkouh

ME

,

Fuster

V.

A polypill strategy to improve adherence: results from the FOCUS project

.

J Am Coll Cardiol

2014

;

64

(

20

):

2071

–

2082

.

324

Nieuwlaat

R

,

Wilczynski

N

,

Navarro

T

,

Hobson

N

,

Jeffery

R

,

Keepanasseril

A

,

Agoritsas

T

,

Mistry

N

,

Iorio

A

,

Jack

S

,

Sivaramalingam

B

,

Iserman

E

,

Mustafa

RA

,

Jedraszewski

D

,

Cotoi

C

,

Haynes

RB.

Interventions for enhancing medication adherence

.

Cochrane Database Syst Rev

2014

;

11

:

CD000011

.

325

Cahill

K

,

Stevens

S

,

Perera

R

,

Lancaster

T.

Pharmacological interventions for smoking cessation: an overview and network meta-analysis

.

Cochrane Database Syst Rev

2013

;

5

:

CD009329

.

326

Hughes

JR

,

Stead

LF

,

Lancaster

T.

Antidepressants for smoking cessation

.

Cochrane Database Syst Rev

2007

;

1

:

CD000031

.

327

Cahill

K

,

Stead

LF

,

Lancaster

T.

Nicotine receptor partial agonists for smoking cessation

.

Cochrane Database Syst Rev

2012

;

4

:

CD006103

.

328

Anderson

L

,

Taylor

RS.

Cardiac rehabilitation for people with heart disease: an overview of Cochrane systematic reviews

.

Cochrane Database Syst Rev

2014

;

12

:

CD011273

.

329

Antithrombotic Trialists Collaboration

,

Baigent

C

,

Blackwell

L

,

Collins

R

,

Emberson

J

,

Godwin

J

,

Peto

R

,

Buring

J

,

Hennekens

C

,

Kearney

P

,

Meade

T

,

Patrono

C

,

Roncaglioni

MC

,

Zanchetti

A.

Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials

.

Lancet

2009

;

373

(

9678

):

1849

–

1860

.

330

CURRENT-OASIS 7 Investigators

,

Mehta

SR

,

Bassand

JP

,

Chrolavicius

S

,

Diaz

R

,

Eikelboom

JW

,

Fox

KA

,

Granger

CB

,

Jolly

S

,

Joyner

CD

,

Rupprecht

HJ

,

Widimsky

P

,

Afzal

R

,

Pogue

J

,

Yusuf

S.

Dose comparisons of clopidogrel and aspirin in acute coronary syndromes

.

N Engl J Med

2010

;

363

(

10

):

930

–

942

.

331

Valgimigli

M

,

Ariotti

S

,

Costa

F.

Duration of dual antiplatelet therapy after drug-eluting stent implantation: will we ever reach a consensus?

Eur Heart J

2015

;

36

(

20

):

1219

–

1222

.

332

Costa

F

,

Tijssen

JG

,

Ariotti

S

,

Giatti

S

,

Moscarella

E

,

Guastaroba

P

,

De Palma

R

,

Ando

G

,

Oreto

G

,

Zijlstra

F

,

Valgimigli

M.

Incremental value of the CRUSADE, ACUITY, and HAS-BLED risk scores for the prediction of hemorrhagic events after coronary stent implantation in patients undergoing long or short duration of dual antiplatelet therapy

.

J Am Heart Assoc

2015

;

4

(

12

):

e002524

.

333

Bonaca

MP

,

Bhatt

DL

,

Cohen

M

,

Steg

PG

,

Storey

RF

,

Jensen

EC

,

Magnani

G

,

Bansilal

S

,

Fish

MP

,

Im

K

,

Bengtsson

O

,

Oude Ophuis

T

,

Budaj

A

,

Theroux

P

,

Ruda

M

,

Hamm

C

,

Goto

S

,

Spinar

J

,

Nicolau

JC

,

Kiss

RG

,

Murphy

SA

,

Wiviott

SD

,

Held

P

,

Braunwald

E

,

Sabatine

MS

,

PEGASUS-TIMI 54 Steering Committee and Investigators

.

Long-term use of ticagrelor in patients with prior myocardial infarction

.

N Engl J Med

2015

;

372

(

19

):

1791

–

1800

.

334

Mauri

L

,

Kereiakes

DJ

,

Yeh

RW

,

Driscoll-Shempp

P

,

Cutlip

DE

,

Steg

PG

,

Normand

SL

,

Braunwald

E

,

Wiviott

SD

,

Cohen

DJ

,

Holmes

DR

Jr,

Krucoff

MW

,

Hermiller

J

,

Dauerman

HL

,

Simon

DI

,

Kandzari

DE

,

Garratt

KN

,

Lee

DP

,

Pow

TK

,

Ver Lee

P

,

Rinaldi

MJ

,

Massaro

JM

,

DAPT Study Investigators

.

Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents

.

N Engl J Med

2014

;

371

(

23

):

2155

–

2166

.

335

Agewall

S

,

Cattaneo

M

,

Collet

JP

,

Andreotti

F

,

Lip

GY

,

Verheugt

FW

,

Huber

K

,

Grove

EL

,

Morais

J

,

Husted

S

,

Wassmann

S

,

Rosano

G

,

Atar

D

,

Pathak

A

,

Kjeldsen

K

,

Storey

RF

,

ESC Working Group on Cardiovascular Pharmacology and Drug Therapy and ESC Working Group on Thrombosis

.

Expert position paper on the use of proton pump inhibitors in patients with cardiovascular disease and antithrombotic therapy

.

Eur Heart J

2013

;

34

(

23

):

1708

–

1713

, 1713a–1713b.

336

Bhatt

DL

,

Cryer

BL

,

Contant

CF

,

Cohen

M

,

Lanas

A

,

Schnitzer

TJ

,

Shook

TL

,

Lapuerta

P

,

Goldsmith

MA

,

Laine

L

,

Scirica

BM

,

Murphy

SA

,

Cannon

CP

,

COGENT Investigators

.

Clopidogrel with or without omeprazole in coronary artery disease

.

N Engl J Med

2010

;

363

(

20

):

1909

–

1917

.

337

Gargiulo

G

,

Costa

F

,

Ariotti

S

,

Biscaglia

S

,

Campo

G

,

Esposito

G

,

Leonardi

S

,

Vranckx

P

,

Windecker

S

,

Valgimigli

M.

Impact of proton pump inhibitors on clinical outcomes in patients treated with a 6- or 24-month dual-antiplatelet therapy duration: Insights from the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY trial

.

Am Heart J

2016

;

174

:

95

–

102

.

338

Mega

JL

,

Braunwald

E

,

Wiviott

SD

,

Bassand

JP

,

Bhatt

DL

,

Bode

C

,

Burton

P

,

Cohen

M

,

Cook-Bruns

N

,

Fox

KA

,

Goto

S

,

Murphy

SA

,

Plotnikov

AN

,

Schneider

D

,

Sun

X

,

Verheugt

FW

,

Gibson

CM

,

ATLAS ACS 2–TIMI 51 Investigators

.

Rivaroxaban in patients with a recent acute coronary syndrome

.

N Engl J Med

2012

;

366

(

1

):

9

–

19

.

339

Palmerini

T

,

Sangiorgi

D

,

Valgimigli

M

,

Biondi-Zoccai

G

,

Feres

F

,

Abizaid

A

,

Costa

RA

,

Hong

MK

,

Kim

BK

,

Jang

Y

,

Kim

HS

,

Park

KW

,

Mariani

A

,

Della Riva

D

,

Genereux

P

,

Leon

MB

,

Bhatt

DL

,

Bendetto

U

,

Rapezzi

C

,

Stone

GW.

Short- versus long-term dual antiplatelet therapy after drug-eluting stent implantation: an individual patient data pairwise and network meta-analysis

.

J Am Coll Cardiol

2015

;

65

(

11

):

1092

–

1102

.

340

Palmerini

T

,

Della Riva

D

,

Benedetto

U

,

Bacchi Reggiani

L

,

Feres

F

,

Abizaid

A

,

Gilard

M

,

Morice

MC

,

Valgimigli

M

,

Hong

MK

,

Kim

BK

,

Jang

Y

,

Kim

HS

,

Park

KW

,

Colombo

A

,

Chieffo

A

,

Sangiorgi

D

,

Biondi-Zoccai

G

,

Genereux

P

,

Angelini

GD

,

Pufulete

M

,

White

J

,

Bhatt

DL

,

Stone

GW.

Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients

.

Eur Heart J

2017

;

38

(

14

):

1034

–

1043

.

341

Reeder

GS

,

Lengyel

M

,

Tajik

AJ

,

Seward

JB

,

Smith

HC

,

Danielson

GK.

Mural thrombus in left ventricular aneurysm: incidence, role of angiography, and relation between anticoagulation and embolization

.

Mayo Clin Proc

1981

;

56

(

2

):

77

–

81

.

342

Keeley

EC

,

Hillis

LD.

Left ventricular mural thrombus after acute myocardial infarction

.

Clinical Cardiology

1996

;

19

(

2

):

83

–

86

.

343

Turpie

AG

,

Robinson

JG

,

Doyle

DJ

,

Mulji

AS

,

Mishkel

GJ

,

Sealey

BJ

,

Cairns

JA

,

Skingley

L

,

Hirsh

J

,

Gent

M.

Comparison of high-dose with low-dose subcutaneous heparin to prevent left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction

.

N Engl J Med

1989

;

320

(

6

):

352

–

357

.

344

Chen

ZM

,

Pan

HC

,

Chen

YP

,

Peto

R

,

Collins

R

,

Jiang

LX

,

Xie

JX

,

Liu

LS

,

COMMIT Collaborative Group

.

Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial

.

Lancet

2005

;

366

(

9497

):

1622

–

1632

.

345

Pfisterer

M

,

Cox

JL

,

Granger

CB

,

Brener

SJ

,

Naylor

CD

,

Califf

RM

,

van de Werf

F

,

Stebbins

AL

,

Lee

KL

,

Topol

EJ

,

Armstrong

PW.

Atenolol use and clinical outcomes after thrombolysis for acute myocardial infarction: the GUSTO-I experience. Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries

.

J Am Coll Cardiol

1998

;

32

(

3

):

634

–

640

.

346

Chatterjee

S

,

Chaudhuri

D

,

Vedanthan

R

,

Fuster

V

,

Ibanez

B

,

Bangalore

S

,

Mukherjee

D.

Early intravenous beta-blockers in patients with acute coronary syndrome—a meta-analysis of randomized trials

.

Int J Cardiol

2013

;

168

(

2

):

915

–

921

.

347

Ibanez

B

,

Macaya

C

,

Sanchez-Brunete

V

,

Pizarro

G

,

Fernandez-Friera

L

,

Mateos

A

,

Fernandez-Ortiz

A

,

Garcia-Ruiz

JM

,

Garcia-Alvarez

A

,

Iniguez

A

,

Jimenez-Borreguero

J

,

Lopez-Romero

P

,

Fernandez-Jimenez

R

,

Goicolea

J

,

Ruiz-Mateos

B

,

Bastante

T

,

Arias

M

,

Iglesias-Vazquez

JA

,

Rodriguez

MD

,

Escalera

N

,

Acebal

C

,

Cabrera

JA

,

Valenciano

J

,

Perez de Prado

A

,

Fernandez-Campos

MJ

,

Casado

I

,

Garcia-Rubira

JC

,

Garcia-Prieto

J

,

Sanz-Rosa

D

,

Cuellas

C

,

Hernandez-Antolin

R

,

Albarran

A

,

Fernandez-Vazquez

F

,

de la Torre-Hernandez

JM

,

Pocock

S

,

Sanz

G

,

Fuster

V.

Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial

.

Circulation

2013

;

128

(

14

):

1495

–

1503

.

348

Pizarro

G

,

Fernandez-Friera

L

,

Fuster

V

,

Fernandez-Jimenez

R

,

Garcia-Ruiz

JM

,

Garcia-Alvarez

A

,

Mateos

A

,

Barreiro

MV

,

Escalera

N

,

Rodriguez

MD

,

de Miguel

A

,

Garcia-Lunar

I

,

Parra-Fuertes

JJ

,

Sanchez-Gonzalez

J

,

Pardillos

L

,

Nieto

B

,

Jimenez

A

,

Abejon

R

,

Bastante

T

,

Martinez de Vega

V

,

Cabrera

JA

,

Lopez-Melgar

B

,

Guzman

G

,

Garcia-Prieto

J

,

Mirelis

JG

,

Zamorano

JL

,

Albarran

A

,

Goicolea

J

,

Escaned

J

,

Pocock

S

,

Iniguez

A

,

Fernandez-Ortiz

A

,

Sanchez-Brunete

V

,

Macaya

C

,

Ibanez

B.

Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction)

.

J Am Coll Cardiol

2014

;

63

(

22

):

2356

–

2362

.

349

Garcia-Prieto

J

,

Villena-Gutierrez

R

,

Gomez

M

,

Bernardo

E

,

Pun-Garcia

A

,

Garcia-Lunar

I

,

Crainiciuc

G

,

Fernandez-Jimenez

R

,

Sreeramkumar

V

,

Bourio-Martinez

R

,

Garcia-Ruiz

JM

,

Del Valle

AS

,

Sanz-Rosa

D

,

Pizarro

G

,

Fernandez-Ortiz

A

,

Hidalgo

A

,

Fuster

V

,

Ibanez

B.

Neutrophil stunning by metoprolol reduces infarct size

.

Nat Commun

2017

;

8

:

14780

.

350

Roolvink

V

,

Ibanez

B

,

Ottervanger

JP

,

Pizarro

G

,

van Royen

N

,

Mateos

A

,

Dambrink

JH

,

Escalera

N

,

Lipsic

E

,

Albarran

A

,

Fernandez-Ortiz

A

,

Fernandez-Aviles

F

,

Goicolea

J

,

Botas

J

,

Remkes

W

,

Hernandez-Jaras

V

,

Kedhi

E

,

Zamorano

JL

,

Navarro

F

,

Alfonso

F

,

Garcia-Lledo

A

,

Alonso

J

,

van Leeuwen

M

,

Nijveldt

R

,

Postma

S

,

Kolkman

E

,

Gosselink

M

,

de Smet

B

,

Rasoul

S

,

Piek

JJ

,

Fuster

V

,

van 't Hof

AW

,

EARLY-BAMI Investigators

.

Early intravenous beta-blockers in patients with ST-segment elevation myocardial infarction before primary percutaneous coronary intervention

.

J Am Coll Cardiol

2016

;

67

(

23

):

2705

–

2715

.

351

Halkin

A

,

Grines

CL

,

Cox

DA

,

Garcia

E

,

Mehran

R

,

Tcheng

JE

,

Griffin

JJ

,

Guagliumi

G

,

Brodie

B

,

Turco

M

,

Rutherford

BD

,

Aymong

E

,

Lansky

AJ

,

Stone

GW.

Impact of intravenous beta-blockade before primary angioplasty on survival in patients undergoing mechanical reperfusion therapy for acute myocardial infarction

.

J Am Coll Cardiol

2004

;

43

(

10

):

1780

–

1787

.

352

Harjai

KJ

,

Stone

GW

,

Boura

J

,

Grines

L

,

Garcia

E

,

Brodie

B

,

Cox

D

,

O'Neill

WW

,

Grines

C.

Effects of prior beta-blocker therapy on clinical outcomes after primary coronary angioplasty for acute myocardial infarction

.

Am J Cardiol

2003

;

91

(

6

):

655

–

660

.

353

Freemantle

N

,

Cleland

J

,

Young

P

,

Mason

J

,

Harrison

J.

Beta blockade after myocardial infarction: systematic review and meta regression analysis

.

BMJ

1999

;

318

(

7200

):

1730

–

1737

.

354

Goldberger

JJ

,

Bonow

RO

,

Cuffe

M

,

Liu

L

,

Rosenberg

Y

,

Shah

PK

,

Smith

SC

Jr,

Subacius

H

,

OBTAIN Investigators

.

Effect of beta-blocker dose on survival after acute myocardial infarction

.

J Am Coll Cardiol

2015

;

66

(

13

):

1431

–

1441

.

355

Andersson

C

,

Shilane

D

,

Go

AS

,

Chang

TI

,

Kazi

D

,

Solomon

MD

,

Boothroyd

DB

,

Hlatky

MA.

Beta-blocker therapy and cardiac events among patients with newly diagnosed coronary heart disease

.

J Am Coll Cardiol

2014

;

64

(

3

):

247

–

252

.

356

Bangalore

S

,

Steg

G

,

Deedwania

P

,

Crowley

K

,

Eagle

KA

,

Goto

S

,

Ohman

EM

,

Cannon

CP

,

Smith

SC

,

Zeymer

U

,

Hoffman

EB

,

Messerli

FH

,

Bhatt

DL

,

REACH Registry Investigators

.

Beta-blocker use and clinical outcomes in stable outpatients with and without coronary artery disease

.

JAMA

2012

;

308

(

13

):

1340

–

1349

.

357

Dargie

HJ.

Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial

.

Lancet

2001

;

357

(

9266

):

1385

–

1390

.

358

The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial

.

Lancet

1999

;

353

(

9146

):

9

–

13

.

359

Packer

M

,

Coats

AJ

,

Fowler

MB

,

Katus

HA

,

Krum

H

,

Mohacsi

P

,

Rouleau

JL

,

Tendera

M

,

Castaigne

A

,

Roecker

EB

,

Schultz

MK

,

DeMets

DL

,

Carvedilol Prospective Randomized Cumulative Survival Study Group

.

Effect of carvedilol on survival in severe chronic heart failure

.

N Engl J Med

2001

;

344

(

22

):

1651

–

1658

.

360

Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)

.

Lancet

1999

;

353

(

9169

):

2001

–

2007

.

361

Flather

MD

,

Shibata

MC

,

Coats

AJ

,

Van Veldhuisen

DJ

,

Parkhomenko

A

,

Borbola

J

,

Cohen

Solal A

,

Dumitrascu

D

,

Ferrari

R

,

Lechat

P

,

Soler-Soler

J

,

Tavazzi

L

,

Spinarova

L

,

Toman

J

,

Bohm

M

,

Anker

SD

,

Thompson

SG

,

Poole

Wilson PA

,

SENIORS Investigators

.

Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS)

.

Eur Heart J

2005

;

26

(

3

):

215

–

225

.

362

Bugiardini

R

,

Cenko

E

,

Ricci

B

,

Vasiljevic

Z

,

Dorobantu

M

,

Kedev

S

,

Vavlukis

M

,

Kalpak

O

,

Puddu

PE

,

Gustiene

O

,

Trninic

D

,

Knezevic

B

,

Milicic

D

,

Gale

CP

,

Manfrini

O

,

Koller

A

,

Badimon

L.

Comparison of early versus delayed oral beta blockers in acute coronary syndromes and effect on outcomes

.

Am J Cardiol

2016

;

117

(

5

):

760

–

767

.

363

Baigent

C

,

Keech

A

,

Kearney

PM

,

Blackwell

L

,

Buck

G

,

Pollicino

C

,

Kirby

A

,

Sourjina

T

,

Peto

R

,

Collins

R

,

Simes

R

,

Cholesterol Treatment Trialists Collaborators

.

Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins

.

Lancet

2005

;

366

(

9493

):

1267

–

1278

.

364

Cannon

CP

,

Braunwald

E

,

McCabe

CH

,

Rader

DJ

,

Rouleau

JL

,

Belder

R

,

Joyal

SV

,

Hill

KA

,

Pfeffer

MA

,

Skene

AM

,

Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators

.

Intensive versus moderate lipid lowering with statins after acute coronary syndromes

.

N Engl J Med

2004

;

350

(

15

):

1495

–

1504

.

365

Schwartz

GG

,

Olsson

AG

,

Ezekowitz

MD

,

Ganz

P

,

Oliver

MF

,

Waters

D

,

Zeiher

A

,

Chaitman

BR

,

Leslie

S

,

Stern

T

,

Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial

.

JAMA

2001

;

285

(

13

):

1711

–

1718

.

366

Cholesterol Treatment Trialists' (CTT) Collaboration

,

Baigent

C

,

Blackwell

L

,

Emberson

J

,

Holland

LE

,

Reith

C

,

Bhala

N

,

Peto

R

,

Barnes

EH

,

Keech

A

,

Simes

J

,

Collins

R.

Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials

.

Lancet

2010

;

376

(

9753

):

1670

–

1681

.

367

Boekholdt

SM

,

Hovingh

GK

,

Mora

S

,

Arsenault

BJ

,

Amarenco

P

,

Pedersen

TR

,

LaRosa

JC

,

Waters

DD

,

DeMicco

DA

,

Simes

RJ

,

Keech

AC

,

Colquhoun

D

,

Hitman

GA

,

Betteridge

DJ

,

Clearfield

MB

,

Downs

JR

,

Colhoun

HM

,

Gotto

AM

Jr,

Ridker

PM

,

Grundy

SM

,

Kastelein

JJ.

Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials

.

J Am Coll Cardiol

2014

;

64

(

5

):

485

–

494

.

368

LaRosa

JC

,

Grundy

SM

,

Waters

DD

,

Shear

C

,

Barter

P

,

Fruchart

JC

,

Gotto

AM

,

Greten

H

,

Kastelein

JJ

,

Shepherd

J

,

Wenger

NK

,

Treating to New Targets Investigators

.

Intensive lipid lowering with atorvastatin in patients with stable coronary disease

.

N Engl J Med

2005

;

352

(

14

):

1425

–

1435

.

369

Cholesterol Treatment Trialists C

,

Fulcher

J

,

O'Connell

R

,

Voysey

M

,

Emberson

J

,

Blackwell

L

,

Mihaylova

B

,

Simes

J

,

Collins

R

,

Kirby

A

,

Colhoun

H

,

Braunwald

E

,

La Rosa

J

,

Pedersen

TR

,

Tonkin

A

,

Davis

B

,

Sleight

P

,

Franzosi

MG

,

Baigent

C

,

Keech

A.

Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials

.

Lancet

2015

;

385

(

9976

):

1397

–

1405

.

370

Shrivastava

AK

,

Singh

HV

,

Raizada

A

,

Singh

SK.

Serial measurement of lipid profile and inflammatory markers in patients with acute myocardial infarction

.

EXCLI J

2015

;

14

:

517

–

526

.

371

Pitt

B

,

Loscalzo

J

,

Ycas

J

,

Raichlen

JS.

Lipid levels after acute coronary syndromes

.

J Am Coll Cardiol

2008

;

51

(

15

):

1440

–

1445

.

372

Sidhu

D

,

Naugler

C.

Fasting time and lipid levels in a community-based population: a cross-sectional study

.

Arch Intern Med

2012

;

172

(

22

):

1707

–

1710

.

373

Food and Drug Administration. FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm, accessed July 26, 2017.

374

Pedersen

TR

,

Cater

NB

,

Faergeman

O

,

Kastelein

JJ

,

Olsson

AG

,

Tikkanen

MJ

,

Holme

I

,

Larsen

ML

,

Lindahl

C

,

Szarek

M.

Comparison of atorvastatin 80 mg/day versus simvastatin 20 to 40 mg/day on frequency of cardiovascular events late (five years) after acute myocardial infarction (from the Incremental Decrease in End Points through Aggressive Lipid Lowering [IDEAL] trial)

.

Am J Cardiol

2010

;

106

(

3

):

354

–

359

.

375

Tikkanen

MJ

,

Szarek

M

,

Fayyad

R

,

Holme

I

,

Cater

NB

,

Faergeman

O

,

Kastelein

JJ

,

Olsson

AG

,

Larsen

ML

,

Lindahl

C

,

Pedersen

TR

,

IDEAL Investigators

.

Total cardiovascular disease burden: comparing intensive with moderate statin therapy insights from the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial

.

J Am Coll Cardiol

2009

;

54

(

25

):

2353

–

2357

.

376

Cannon

CP

,

Blazing

MA

,

Giugliano

RP

,

McCagg

A

,

White

JA

,

Theroux

P

,

Darius

H

,

Lewis

BS

,

Ophuis

TO

,

Jukema

JW

,

De Ferrari

GM

,

Ruzyllo

W

,

De Lucca

P

,

Im

K

,

Bohula

EA

,

Reist

C

,

Wiviott

SD

,

Tershakovec

AM

,

Musliner

TA

,

Braunwald

E

,

Califf

RM

,

IMPROVE-IT Investigators

.

Ezetimibe added to statin therapy after acute coronary syndromes

.

N Engl J Med

2015

;

372

(

25

):

2387

–

2397

.

377

Li

C

,

Lin

L

,

Zhang

W

,

Zhou

L

,

Wang

H

,

Luo

X

,

Luo

H

,

Cai

Y

,

Zeng

C.

Efficiency and safety of proprotein convertase subtilisin/kexin 9 monoclonal antibody on hypercholesterolemia: a meta-analysis of 20 randomized controlled trials

.

J Am Heart Assoc

2015

;

4

(

6

):

e001937

.

378

Zhang

XL

,

Zhu

QQ

,

Zhu

L

,

Chen

JZ

,

Chen

QH

,

Li

GN

,

Xie

J

,

Kang

LN

,

Xu

B.

Safety and efficacy of anti-PCSK9 antibodies: a meta-analysis of 25 randomized, controlled trials

.

BMC Med

2015

;

13

:

123

.

379

Sabatine

MS

,

Giugliano

RP

,

Wiviott

SD

,

Raal

FJ

,

Blom

DJ

,

Robinson

J

,

Ballantyne

CM

,

Somaratne

R

,

Legg

J

,

Wasserman

SM

,

Scott

R

,

Koren

MJ

,

Stein

EA

,

Open-Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) Investigators

.

Efficacy and safety of evolocumab in reducing lipids and cardiovascular events

.

N Engl J Med

2015

;

372

(

16

):

1500

–

1509

.

380

Robinson

JG

,

Farnier

M

,

Krempf

M

,

Bergeron

J

,

Luc

G

,

Averna

M

,

Stroes

ES

,

Langslet

G

,

Raal

FJ

,

El Shahawy

M

,

Koren

MJ

,

Lepor

NE

,

Lorenzato

C

,

Pordy

R

,

Chaudhari

U

,

Kastelein

JJ

,

ODYSSEY LONG TERM Investigators

.

Efficacy and safety of alirocumab in reducing lipids and cardiovascular events

.

N Engl J Med

2015

;

372

(

16

):

1489

–

1499

.

381

Navarese

EP

,

Kolodziejczak

M

,

Schulze

V

,

Gurbel

PA

,

Tantry

U

,

Lin

Y

,

Brockmeyer

M

,

Kandzari

DE

,

Kubica

JM

,

D'Agostino

RB

Sr.,

Kubica

J

,

Volpe

M

,

Agewall

S

,

Kereiakes

DJ

,

Kelm

M.

Effects of proprotein convertase subtilisin/kexin type 9 antibodies in adults with hypercholesterolemia: a systematic review and meta-analysis

.

Ann Intern Med

2015

;

163

(

1

):

40

–

51

.

382

Sabatine

MS

,

Giugliano

RP

,

Keech

AC

,

Honarpour

N

,

Wiviott

SD

,

Murphy

SA

,

Kuder

JF

,

Wang

H

,

Liu

T

,

Wasserman

SM

,

Sever

PS

,

Pedersen

TR

,

FOURIER Steering Committee and Investigators

.

Evolocumab and clinical outcomes in patients with cardiovascular disease

.

N Engl J Med

2017

;

376

(

18

):

1713

–

1722

.

383

ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group

.

ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction

.

Lancet

1995

;

345

(

8951

):

669

–

685

.

384

Yusuf

S

,

Held

P

,

Furberg

C.

Update of effects of calcium antagonists in myocardial infarction or angina in light of the second Danish Verapamil Infarction Trial (DAVIT-II) and other recent studies

.

Am J Cardiol

1991

;

67

(

15

):

1295

–

1297

.

385

Held

PH

,

Yusuf

S

,

Furberg

CD.

Calcium channel blockers in acute myocardial infarction and unstable angina: an overview

.

BMJ

1989

;

299

(

6709

):

1187

–

1192

.

386

Effect of verapamil on mortality and major events after acute myocardial infarction (the Danish Verapamil Infarction Trial II--DAVIT II)

.

Am J Cardiol

1990

;

66

(

10

):

779

–

785

.

387

Furberg

CD

,

Psaty

BM

,

Meyer

JV.

Nifedipine. Dose-related increase in mortality in patients with coronary heart disease

.

Circulation

1995

;

92

(

5

):

1326

–

1331

.

388

Poole-Wilson

PA

,

Lubsen

J

,

Kirwan

BA

,

van Dalen

FJ

,

Wagener

G

,

Danchin

N

,

Just

H

,

Fox

KA

,

Pocock

SJ

,

Clayton

TC

,

Motro

M

,

Parker

JD

,

Bourassa

MG

,

Dart

AM

,

Hildebrandt

P

,

Hjalmarson

A

,

Kragten

JA

,

Molhoek

GP

,

Otterstad

JE

,

Seabra-Gomes

R

,

Soler-Soler

J

,

Weber

S

,

Coronary Disease Trial Investigating Outcome with Nifedipine Gastrointestinal Therapeutic System Investigators

.

Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial

.

Lancet

2004

;

364

(

9437

):

849

–

857

.

389

Pfeffer

MA

,

Greaves

SC

,

Arnold

JM

,

Glynn

RJ

,

LaMotte

FS

,

Lee

RT

,

Menapace

FJ

Jr,

Rapaport

E

,

Ridker

PM

,

Rouleau

JL

,

Solomon

SD

,

Hennekens

CH.

Early versus delayed angiotensin-converting enzyme inhibition therapy in acute myocardial infarction. The healing and early afterload reducing therapy trial

.

Circulation

1997

;

95

(

12

):

2643

–

2651

.

390

Kober

L

,

Torp-Pedersen

C

,

Carlsen

JE

,

Bagger

H

,

Eliasen

P

,

Lyngborg

K

,

Videbaek

J

,

Cole

DS

,

Auclert

L

,

Pauly

NC.

A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group

.

N Engl J Med

1995

;

333

(

25

):

1670

–

1676

.

391

Ball

SG

,

Hall

AS

,

Murray

GD.

ACE inhibition, atherosclerosis and myocardial infarction—the AIRE Study in practice. Acute Infarction Ramipril Efficacy Study

.

Eur Heart J

1994

;

15

(Suppl B)

:

20

–

5

; discussion 26–30.

392

Pfeffer

MA

,

Braunwald

E

,

Moye

LA

,

Basta

L

,

Brown

EJ

Jr,

Cuddy

TE

,

Davis

BR

,

Geltman

EM

,

Goldman

S

,

Flaker

GC

,

Klein

M

,

Lamas

GA

,

Packer

M

,

Rouleau

J

,

Rouleau

JL

,

Rutherford

J

,

Wertheimer

JH

,

Hawkins

CM

,

SAVE Investigators

.

Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators

.

N Engl J Med

1992

;

327

(

10

):

669

–

677

.

393

ACE Inhibitor Myocardial Infarction Collaborative Group

.

Indications for ACE inhibitors in the early treatment of acute myocardial infarction: systematic overview of individual data from 100,000 patients in randomized trials

.

Circulation

1998

;

97

(

22

):

2202

–

2212

.

394

Fox

KM

,

EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators

.

Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study)

.

Lancet

2003

;

362

(

9386

):

782

–

788

.

395

Yusuf

S

,

Sleight

P

,

Pogue

J

,

Bosch

J

,

Davies

R

,

Dagenais

G.

Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators

.

N Engl J Med

2000

;

342

(

3

):

145

–

153

.

396

Pfeffer

MA

,

McMurray

JJ

,

Velazquez

EJ

,

Rouleau

JL

,

Kober

L

,

Maggioni

AP

,

Solomon

SD

,

Swedberg

K

,

Van de Werf

F

,

White

H

,

Leimberger

JD

,

Henis

M

,

Edwards

S

,

Zelenkofske

S

,

Sellers

MA

,

Califf

RM

,

Valsartan in Acute Myocardial Infarction Trial Investigators

.

Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both

.

N Engl J Med

2003

;

349

(

20

):

1893

–

1906

.

397

Pitt

B

,

Remme

W

,

Zannad

F

,

Neaton

J

,

Martinez

F

,

Roniker

B

,

Bittman

R

,

Hurley

S

,

Kleiman

J

,

Gatlin

M

,

Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators

.

Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction

.

N Engl J Med

2003

;

348

(

14

):

1309

–

1321

.

398

Pitt

B

,

Zannad

F

,

Remme

WJ

,

Cody

R

,

Castaigne

A

,

Perez

A

,

Palensky

J

,

Wittes

J.

The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators

.

N Engl J Med

1999

;

341

(

10

):

709

–

717

.

399

Zannad

F

,

McMurray

JJ

,

Krum

H

,

van Veldhuisen

DJ

,

Swedberg

K

,

Shi

H

,

Vincent

J

,

Pocock

SJ

,

Pitt

B

,

EMPHASIS-HF Study Group

.

Eplerenone in patients with systolic heart failure and mild symptoms

.

N Engl J Med

2011

;

364

(

1

):

11

–

21

.

400

Girerd

N

,

Collier

T

,

Pocock

S

,

Krum

H

,

McMurray

JJ

,

Swedberg

K

,

Van Veldhuisen

DJ

,

Vincent

J

,

Pitt

B

,

Zannad

F.

Clinical benefits of eplerenone in patients with systolic heart failure and mild symptoms when initiated shortly after hospital discharge: analysis from the EMPHASIS-HF trial

.

Eur Heart J

2015

;

36

(

34

):

2310

–

2317

.

401

Montalescot

G

,

Pitt

B

,

Lopez de Sa

E

,

Hamm

CW

,

Flather

M

,

Verheugt

F

,

Shi

H

,

Turgonyi

E

,

Orri

M

,

Vincent

J

,

Zannad

F

,

REMINDER Investigators

.

Early eplerenone treatment in patients with acute ST-elevation myocardial infarction without heart failure: the Randomized Double-Blind Reminder Study

.

Eur Heart J

2014

;

35

(

34

):

2295

–

2302

.

402

Beygui

F

,

Cayla

G

,

Roule

V

,

Roubille

F

,

Delarche

N

,

Silvain

J

,

Van Belle

E

,

Belle

L

,

Galinier

M

,

Motreff

P

,

Cornillet

L

,

Collet

JP

,

Furber

A

,

Goldstein

P

,

Ecollan

P

,

Legallois

D

,

Lebon

A

,

Rousseau

H

,

Machecourt

J

,

Zannad

F

,

Vicaut

E

,

Montalescot

G

,

ALBATROSS Investigators

.

Early aldosterone blockade in acute myocardial infarction: the ALBATROSS Randomized Clinical Trial

.

J Am Coll Cardiol

2016

;

67

(

16

):

1917

–

1927

.

403

Garcia-Ruiz

JM

,

Fernandez-Jimenez

R

,

Garcia-Alvarez

A

,

Pizarro

G

,

Galan-Arriola

C

,

Fernandez-Friera

L

,

Mateos

A

,

Nuno-Ayala

M

,

Aguero

J

,

Sanchez-Gonzalez

J

,

Garcia-Prieto

J

,

Lopez-Melgar

B

,

Martinez-Tenorio

P

,

Lopez-Martin

GJ

,

Macias

A

,

Perez-Asenjo

B

,

Cabrera

JA

,

Fernandez-Ortiz

A

,

Fuster

V

,

Ibanez

B.

Impact of the timing of metoprolol administration during STEMI on infarct size and ventricular function

.

J Am Coll Cardiol

2016

;

67

(

18

):

2093

–

2104

.

404

Bangalore

S

,

Makani

H

,

Radford

M

,

Thakur

K

,

Toklu

B

,

Katz

SD

,

DiNicolantonio

JJ

,

Devereaux

PJ

,

Alexander

KP

,

Wetterslev

J

,

Messerli

FH.

Clinical outcomes with beta-blockers for myocardial infarction: a meta-analysis of randomized trials

.

Am J Med

2014

;

127

(

10

):

939

–

53

.

405

Huang

BT

,

Huang

FY

,

Zuo

ZL

,

Liao

YB

,

Heng

Y

,

Wang

PJ

,

Gui

YY

,

Xia

TL

,

Xin

ZM

,

Liu

W

,

Zhang

C

,

Chen

SJ

,

Pu

XB

,

Chen

M

,

Huang

DJ.

Meta-analysis of relation between oral beta-blocker therapy and outcomes in patients with acute myocardial infarction who underwent percutaneous coronary intervention

.

Am J Cardiol

2015

;

115

(

11

):

1529

–

1538

.

406

Authors/Task Force Members

,

Catapano

AL

,

Graham

I

,

De Backer

G

,

Wiklund

O

,

Chapman

MJ

,

Drexel

H

,

Hoes

AW

,

Jennings

CS

,

Landmesser

U

,

Pedersen

TR

,

Reiner

Z

,

Riccardi

G

,

Taskinen

MR

,

Tokgozoglu

L

,

Verschuren

WM

,

Vlachopoulos

C

,

Wood

DA

,

Zamorano

JL.

2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR)

.

Atherosclerosis

2016

;

253

:

281

–

344

.

407

Dickstein

K

,

Kjekshus

J

,

Optimaal Steering Committee of the OPTIMAAL Study Group

.

Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan

.

Lancet

2002

;

360

(

9335

):

752

–

760

.

408

Iakobishvili

Z

,

Cohen

E

,

Garty

M

,

Behar

S

,

Shotan

A

,

Sandach

A

,

Gottlieb

S

,

Mager

A

,

Battler

A

,

Hasdai

D

,

Heart Failure Survey in Isarel Investigators

.

Use of intravenous morphine for acute decompensated heart failure in patients with and without acute coronary syndromes

.

Acute Card Care

2011

;

13

(

2

):

76

–

80

.

409

Peacock

WF

,

Hollander

JE

,

Diercks

DB

,

Lopatin

M

,

Fonarow

G

,

Emerman

CL.

Morphine and outcomes in acute decompensated heart failure: an ADHERE analysis

.

Emerg Med J

2008

;

25

(

4

):

205

–

209

.

410

Weng

CL

,

Zhao

YT

,

Liu

QH

,

Fu

CJ

,

Sun

F

,

Ma

YL

,

Chen

YW

,

He

QY.

Meta-analysis: noninvasive ventilation in acute cardiogenic pulmonary edema

.

Ann Intern Med

2010

;

152

(

9

):

590

–

600

.

411

Vital

FM

,

Ladeira

MT

,

Atallah

AN.

Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema

.

Cochrane Database Syst Rev

2013

;

5

:

CD005351

.

412

McAlister

FA

,

Stewart

S

,

Ferrua

S

,

McMurray

JJ.

Multidisciplinary strategies for the management of heart failure patients at high risk for admission: a systematic review of randomized trials

.

J Am Coll Cardiol

2004

;

44

(

4

):

810

–

819

.

413

The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators

.

Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure

.

Lancet

1993

;

342

(

8875

):

821

–

828

.

414

Hjalmarson

A

,

Goldstein

S

,

Fagerberg

B

,

Wedel

H

,

Waagstein

F

,

Kjekshus

J

,

Wikstrand

J

,

El Allaf

D

,

Vitovec

J

,

Aldershvile

J

,

Halinen

M

,

Dietz

R

,

Neuhaus

KL

,

Janosi

A

,

Thorgeirsson

G

,

Dunselman

PH

,

Gullestad

L

,

Kuch

J

,

Herlitz

J

,

Rickenbacher

P

,

Ball

S

,

Gottlieb

S

,

Deedwania

P.

Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group

.

JAMA

2000

;

283

(

10

):

1295

–

1302

.

415

Packer

M

,

Bristow

MR

,

Cohn

JN

,

Colucci

WS

,

Fowler

MB

,

Gilbert

EM

,

Shusterman

NH.

The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group

.

N Engl J Med

1996

;

334

(

21

):

1349

–

1355

.

416

Packer

M

,

Fowler

MB

,

Roecker

EB

,

Coats

AJ

,

Katus

HA

,

Krum

H

,

Mohacsi

P

,

Rouleau

JL

,

Tendera

M

,

Staiger

C

,

Holcslaw

TL

,

Amann-Zalan

I

,

DeMets

DL

,

Carvedilol Prospective Randomized Cumulative Survival Study Group

.

Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study

.

Circulation

2002

;

106

(

17

):

2194

–

2199

.

417

Gray

AJ

,

Goodacre

S

,

Newby

DE

,

Masson

MA

,

Sampson

F

,

Dixon

S

,

Crane

S

,

Elliott

M

,

Nicholl

J

,

3CPO Study Investigators

.

A multicentre randomised controlled trial of the use of continuous positive airway pressure and non-invasive positive pressure ventilation in the early treatment of patients presenting to the emergency department with severe acute cardiogenic pulmonary oedema: the 3CPO trial

.

Health Technol Assess

2009

;

13

(

33

):

1

–

106

.

418

Park

M

,

Sangean

MC

,

Volpe Mde

S

,

Feltrim

MI

,

Nozawa

E

,

Leite

PF

,

Passos Amato

MB

,

Lorenzi-Filho

G.

Randomized, prospective trial of oxygen, continuous positive airway pressure, and bilevel positive airway pressure by face mask in acute cardiogenic pulmonary edema

.

Crit Care Med

2004

;

32

(

12

):

2407

–

2415

.

419

Gray

A

,

Goodacre

S

,

Newby

DE

,

Masson

M

,

Sampson

F

,

Nicholl

J

,

3CPO Trialists

.

Noninvasive ventilation in acute cardiogenic pulmonary edema

.

N Engl J Med

2008

;

359

(

2

):

142

–

51

.

420

Harjola

VP

,

Mebazaa

A

,

Celutkiene

J

,

Bettex

D

,

Bueno

H

,

Chioncel

O

,

Crespo-Leiro

MG

,

Falk

V

,

Filippatos

G

,

Gibbs

S

,

Leite-Moreira

A

,

Lassus

J

,

Masip

J

,

Mueller

C

,

Mullens

W

,

Naeije

R

,

Nordegraaf

AV

,

Parissis

J

,

Riley

JP

,

Ristic

A

,

Rosano

G

,

Rudiger

A

,

Ruschitzka

F

,

Seferovic

P

,

Sztrymf

B

,

Vieillard-Baron

A

,

Yilmaz

MB

,

Konstantinides

S.

Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology

.

Eur J Heart Fail

2016

;

18

(

3

):

226

–

241

.

421

Goldberg

RJ

,

Spencer

FA

,

Gore

JM

,

Lessard

D

,

Yarzebski

J.

Thirty-year trends (1975 to 2005) in the magnitude of, management of, and hospital death rates associated with cardiogenic shock in patients with acute myocardial infarction a population-based perspective

.

Circulation

2009

;

119

(

9

):

1211

–

1219

.

422

Picard

MH

,

Davidoff

R

,

Sleeper

LA

,

Mendes

LA

,

Thompson

CR

,

Dzavik

V

,

Steingart

R

,

Gin

K

,

White

HD

,

Hochman

JS

,

SHOCK Trial

.

Echocardiographic predictors of survival and response to early revascularization in cardiogenic shock

.

Circulation

2003

;

107

(

2

):

279

–

284

.

423

Engstrom

AE

,

Vis

MM

,

Bouma

BJ

,

van den Brink

RBA

,

Baan

J

,

Claessen

B

,

Kikkert

WJ

,

Sjauw

KD

,

Meuwissen

M

,

Koch

KT

,

de Winter

RJ

,

Tijssen

JGP

,

Piek

JJ

,

Henriques

JPS.

Right ventricular dysfunction is an independent predictor for mortality in ST-elevation myocardial infarction patients presenting with cardiogenic shock on admission

.

Eur J Heart Fail

2010

;

12

(

3

):

276

–

282

.

424

Jeger

RV

,

Lowe

AM

,

Buller

CE

,

Pfisterer

ME

,

Dzavik

V

,

Webb

JG

,

Hochman

JS

,

Jorde

UP

,

SHOCK Investigators

.

Hemodynamic parameters are prognostically important in cardiogenic shock but similar following early revascularization or initial medical stabilization: a report from the SHOCK trial

.

Chest

2007

;

132

(

6

):

1794

–

1803

.

425

Hochman

JS

,

Alexander

JH

,

Reynolds

HR

,

Stebbins

AL

,

Dzavik

V

,

Harrington

RA

,

de Werf

FV

,

TRIUMPH Investigators

.

Effect of tilarginine acetate in patients with acute myocardial infarction and cardiogenic shock: the TRIUMPH randomized controlled trial

.

JAMA

2007

;

297

(

15

):

1657

–

1666

.

426

Lancellotti

P

,

Price

S

,

Edvardsen

T

,

Cosyns

B

,

Neskovic

AN

,

Dulgheru

R

,

Flachskampf

FA

,

Hassager

C

,

Pasquet

A

,

Gargani

L

,

Galderisi

M

,

Cardim

N

,

Haugaa

KH

,

Ancion

A

,

Zamorano

JL

,

Donal

E

,

Bueno

H

,

Habib

G.

The use of echocardiography in acute cardiovascular care: Recommendations of the European Association of Cardiovascular Imaging and the Acute Cardiovascular Care Association

.

Eur Heart J Acute Cardiovasc Care

2015

;

4

(

1

):

3

–

5

.

427

Hussain

F

,

Philipp

RK

,

Ducas

RA

,

Elliott

J

,

Dzavik

V

,

Jassal

DS

,

Tam

JW

,

Roberts

D

,

Garber

PJ

,

Ducas

J.

The ability to achieve complete revascularization is associated with improved in-hospital survival in cardiogenic shock due to myocardial infarction: Manitoba cardiogenic SHOCK Registry investigators

.

Catheter Cardiovasc Interv

2011

;

78

(

4

):

540

–

548

.

428

De Backer

D

,

Biston

P

,

Devriendt

J

,

Madl

C

,

Chochrad

D

,

Aldecoa

C

,

Brasseur

A

,

Defrance

P

,

Gottignies

P

,

Vincent

JL

,

SOAP II Investigators

.

Comparison of dopamine and norepinephrine in the treatment of shock

.

N Engl J Med

2010

;

362

(

9

):

779

–

789

.

429

Ouweneel

DM

,

Eriksen

E

,

Sjauw

KD

,

van Dongen

IM

,

Hirsch

A

,

Packer

EJ

,

Vis

MM

,

Wykrzykowska

JJ

,

Koch

KT

,

Baan

J

,

de Winter

RJ

,

Piek

JJ

,

Lagrand

WK

,

de Mol

BA

,

Tijssen

JG

,

Henriques

JP.

Percutaneous mechanical circulatory support versus intra-aortic balloon pump in cardiogenic shock after acute myocardial infarction

.

J Am Coll Cardiol

2017

;

69

(

3

):

278

–

287

.

430

Cheng

JM

,

den Uil

CA

,

Hoeks

SE

,

van der Ent

M

,

Jewbali

LS

,

van Domburg

RT

,

Serruys

PW.

Percutaneous left ventricular assist devices vs. intra-aortic balloon pump counterpulsation for treatment of cardiogenic shock: a meta-analysis of controlled trials

.

Eur Heart J

2009

;

30

(

17

):

2102

–

2108

.

431

Starling

RC

,

Naka

Y

,

Boyle

AJ

,

Gonzalez-Stawinski

G

,

John

R

,

Jorde

U

,

Russell

SD

,

Conte

JV

,

Aaronson

KD

,

McGee

EC

,

Cotts

WG

,

DeNofrio

D

,

Duc

TP

,

Farrar

DJ

,

Pagani

FD.

Results of the post-US Food and Drug Administration-approval study with a continuous flow left ventricular assist device as a bridge to heart transplantation. A prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support)

.

J Am Coll Cardiol

2011

;

57

(

19

):

1890

–

1898

.

432

Sheu

JJ

,

Tsai

TH

,

Lee

FY

,

Fang

HY

,

Sun

CK

,

Leu

S

,

Yang

CH

,

Chen

SM

,

Hang

CL

,

Hsieh

YK

,

Chen

CJ

,

Wu

CJ

,

Yip

HK.

Early extracorporeal membrane oxygenator-assisted primary percutaneous coronary intervention improved 30-day clinical outcomes in patients with ST-segment elevation myocardial infarction complicated with profound cardiogenic shock

.

Crit Care Med

2010

;

38

(

9

):

1810

–

1817

.

433

Shah

MR

,

Hasselblad

V

,

Stevenson

LW

,

Binanay

C

,

O'Connor

CM

,

Sopko

G

,

Califf

RM.

Impact of the pulmonary artery catheter in critically ill patients: meta-analysis of randomized clinical trials

.

JAMA

2005

;

294

(

13

):

1664

–

1670

.

434

Bart

BA

,

Goldsmith

SR

,

Lee

KL

,

Givertz

MM

,

O'Connor

CM

,

Bull

DA

,

Redfield

MM

,

Deswal

A

,

Rouleau

JL

,

LeWinter

MM

,

Ofili

EO

,

Stevenson

LW

,

Semigran

MJ

,

Felker

GM

,

Chen

HH

,

Hernandez

AF

,

Anstrom

KJ

,

McNulty

SE

,

Velazquez

EJ

,

Ibarra

JC

,

Mascette

AM

,

Braunwald

E

,

Heart Failure Clinical Research Network

.

Ultrafiltration in decompensated heart failure with cardiorenal syndrome

.

N Engl J Med

2012

;

367

(

24

):

2296

–

2304

.

435

Costanzo

MR

,

Guglin

ME

,

Saltzberg

MT

,

Jessup

ML

,

Bart

BA

,

Teerlink

JR

,

Jaski

BE

,

Fang

JC

,

Feller

ED

,

Haas

GJ

,

Anderson

AS

,

Schollmeyer

MP

,

Sobotka

PA

,

UNLOAD Trial Investigators

.

Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure

.

J Am Coll Cardiol

2007

;

49

(

6

):

675

–

683

.

436

Costanzo

MR

,

Saltzberg

MT

,

Jessup

M

,

Teerlink

JR

,

Sobotka

PA

,

Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure (UNLOAD) Investigators

.

Ultrafiltration is associated with fewer rehospitalizations than continuous diuretic infusion in patients with decompensated heart failure: results from UNLOAD

.

J Card Fail

2010

;

16

(

4

):

277

–

284

.

437

Buerke

M

,

Prondzinsky

R

,

Lemm

H

,

Dietz

S

,

Buerke

U

,

Ebelt

H

,

Bushnaq

H

,

Silber

RE

,

Werdan

K.

Intra-aortic balloon counterpulsation in the treatment of infarction-related cardiogenic shock—review of the current evidence

.

Artif Organs

2012

;

36

(

6

):

505

–

511

.

438

Gorenek

B

,

Blomstrom Lundqvist

C

,

Brugada Terradellas

J

,

Camm

AJ

,

Hindricks

G

,

Huber

K

,

Kirchhof

P

,

Kuck

KH

,

Kudaiberdieva

G

,

Lin

T

,

Raviele

A

,

Santini

M

,

Tilz

RR

,

Valgimigli

M

,

Vos

MA

,

Vrints

C

,

Zeymer

U

,

Lip

GY

,

Potpara

T

,

Fauchier

L

,

Sticherling

C

,

Roffi

M

,

Widimsky

P

,

Mehilli

J

,

Lettino

M

,

Schiele

F

,

Sinnaeve

P

,

Boriani

G

,

Lane

D

,

Savelieva

I

,

European Heart Rhythm Association

,

Acute Cardiovascular Care Association

,

European Association of Percutaneous Cardiovascular Interventions

.

Cardiac arrhythmias in acute coronary syndromes: position paper from the joint EHRA, ACCA, and EAPCI task force

.

Europace

2014

;

16

(

11

):

1655

–

1673

.

439

Piccini

JP

,

Schulte

PJ

,

Pieper

KS

,

Mehta

RH

,

White

HD

,

Van de Werf

F

,

Ardissino

D

,

Califf

RM

,

Granger

CB

,

Ohman

EM

,

Alexander

JH.

Antiarrhythmic drug therapy for sustained ventricular arrhythmias complicating acute myocardial infarction

.

Crit Care Med

2011

;

39

(

1

):

78

–

83

.

440

Piers

SR

,

Wijnmaalen

AP

,

Borleffs

CJ

,

van Huls van Taxis

CF

,

Thijssen

J

,

van Rees

JB

,

Cannegieter

SC

,

Bax

JJ

,

Schalij

MJ

,

Zeppenfeld

K.

Early reperfusion therapy affects inducibility, cycle length, and occurrence of ventricular tachycardia late after myocardial infarction

.

Circ Arrhythm Electrophysiol

2011

;

4

(

2

):

195

–

201

.

441

Nalliah

CJ

,

Zaman

S

,

Narayan

A

,

Sullivan

J

,

Kovoor

P.

Coronary artery reperfusion for ST elevation myocardial infarction is associated with shorter cycle length ventricular tachycardia and fewer spontaneous arrhythmias

.

Europace

2014

;

16

(

7

):

1053

–

1060

.

442

Liang

JJ

,

Fender

EA

,

Cha

YM

,

Lennon

RJ

,

Prasad

A

,

Barsness

GW.

Long-term outcomes in survivors of early ventricular arrhythmias after acute ST-elevation and non-ST-elevation myocardial infarction treated with percutaneous coronary intervention

.

Am J Cardiol

2016

;

117

(

5

):

709

–

713

.

443

Danchin

N

,

Fauchier

L

,

Marijon

E

,

Barnay

C

,

Furber

A

,

Mabo

P

,

Bernard

P

,

Blanc

JJ

,

Jouven

X

,

Le Heuzey

JY

,

Charbonnier

B

,

Ferrieres

J

,

Simon

T

,

French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) Investigators

.

Impact of early statin therapy on development of atrial fibrillation at the acute stage of myocardial infarction: data from the FAST-MI register

.

Heart

2010

;

96

(

22

):

1809

–

1814

.

444

Schmitt

J

,

Duray

G

,

Gersh

BJ

,

Hohnloser

SH.

Atrial fibrillation in acute myocardial infarction: a systematic review of the incidence, clinical features and prognostic implications

.

Eur Heart J

2009

;

30

(

9

):

1038

–

1045

.

445

Batra

G

,

Svennblad

B

,

Held

C

,

Jernberg

T

,

Johanson

P

,

Wallentin

L

,

Oldgren

J.

All types of atrial fibrillation in the setting of myocardial infarction are associated with impaired outcome

.

Heart

2016

;

102

(

12

):

926

–

933

.

446

Nilsson

KR

Jr,

Al-Khatib

SM

,

Zhou

Y

,

Pieper

K

,

White

HD

,

Maggioni

AP

,

Kober

L

,

Granger

CB

,

Lewis

EF

,

McMurray

JJ

,

Califf

RM

,

Velazquez

EJ.

Atrial fibrillation management strategies and early mortality after myocardial infarction: results from the Valsartan in Acute Myocardial Infarction (VALIANT) Trial

.

Heart

2010

;

96

(

11

):

838

–

842

.

447

Jabre

P

,

Jouven

X

,

Adnet

F

,

Thabut

G

,

Bielinski

SJ

,

Weston

SA

,

Roger

VL.

Atrial fibrillation and death after myocardial infarction: a community study

.

Circulation

2011

;

123

(

19

):

2094

–

100

.

448

Siu

CW

,

Jim

MH

,

Ho

HH

,

Miu

R

,

Lee

SW

,

Lau

CP

,

Tse

HF.

Transient atrial fibrillation complicating acute inferior myocardial infarction: implications for future risk of ischemic stroke

.

Chest

2007

;

132

(

1

):

44

–

49

.

449

Segal

JB

,

McNamara

RL

,

Miller

MR

,

Kim

N

,

Goodman

SN

,

Powe

NR

,

Robinson

K

,

Yu

D

,

Bass

EB.

The evidence regarding the drugs used for ventricular rate control

.

J Fam Pract

2000

;

49

(

1

):

47

–

59

.

450

Hou

ZY

,

Chang

MS

,

Chen

CY

,

Tu

MS

,

Lin

SL

,

Chiang

HT

,

Woosley

RL.

Acute treatment of recent-onset atrial fibrillation and flutter with a tailored dosing regimen of intravenous amiodarone. A randomized, digoxin-controlled study

.

Eur Heart J

1995

;

16

(

4

):

521

–

528

.

451

Metawee

M

,

Charnigo

R

,

Morales

G

,

Darrat

Y

,

Sorrell

V

,

Di Biase

L

,

Natale

A

,

Delisle

B

,

Elayi

CS

;

Magic Investigators

.

Digoxin and short term mortality after acute STEMI: results from the MAGIC trial

.

Int J Cardiol

2016

;

218

:

176

–

180

.

452

Jordaens

L

,

Trouerbach

J

,

Calle

P

,

Tavernier

R

,

Derycke

E

,

Vertongen

P

,

Bergez

B

,

Vandekerckhove

Y.

Conversion of atrial fibrillation to sinus rhythm and rate control by digoxin in comparison to placebo

.

Eur Heart J

1997

;

18

(

4

):

643

–

648

.

453

Thomas

SP

,

Guy

D

,

Wallace

E

,

Crampton

R

,

Kijvanit

P

,

Eipper

V

,

Ross

DL

,

Cooper

MJ.

Rapid loading of sotalol or amiodarone for management of recent onset symptomatic atrial fibrillation: a randomized, digoxin-controlled trial

.

Am Heart J

2004

;

147

(

1

):

E3

.

454

Piccini

JP

,

Hranitzky

PM

,

Kilaru

R

,

Rouleau

JL

,

White

HD

,

Aylward

PE

,

Van de Werf

F

,

Solomon

SD

,

Califf

RM

,

Velazquez

EJ.

Relation of mortality to failure to prescribe beta blockers acutely in patients with sustained ventricular tachycardia and ventricular fibrillation following acute myocardial infarction (from the VALsartan In Acute myocardial iNfarcTion trial [VALIANT] Registry)

.

Am J Cardiol

2008

;

102

(

11

):

1427

–

1432

.

455

Zafari

AM

,

Zarter

SK

,

Heggen

V

,

Wilson

P

,

Taylor

RA

,

Reddy

K

,

Backscheider

AG

,

Dudley

SC

Jr.

A program encouraging early defibrillation results in improved in-hospital resuscitation efficacy

.

J Am Coll Cardiol

2004

;

44

(

4

):

846

–

852

.

456

Wolfe

CL

,

Nibley

C

,

Bhandari

A

,

Chatterjee

K

,

Scheinman

M.

Polymorphous ventricular tachycardia associated with acute myocardial infarction

.

Circulation

1991

;

84

(

4

):

1543

–

1551

.

457

Mehta

RH

,

Yu

J

,

Piccini

JP

,

Tcheng

JE

,

Farkouh

ME

,

Reiffel

J

,

Fahy

M

,

Mehran

R

,

Stone

GW.

Prognostic significance of postprocedural sustained ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention (from the HORIZONS-AMI Trial)

.

Am J Cardiol

2012

;

109

(

6

):

805

–

812

.

458

Masuda

M

,

Nakatani

D

,

Hikoso

S

,

Suna

S

,

Usami

M

,

Matsumoto

S

,

Kitamura

T

,

Minamiguchi

H

,

Okuyama

Y

,

Uematsu

M

,

Yamada

T

,

Iwakura

K

,

Hamasaki

T

,

Sakata

Y

,

Sato

H

,

Nanto

S

,

Hori

M

,

Komuro

I

,

Sakata

Y

,

OACIS investigators

.

Clinical impact of ventricular tachycardia and/or fibrillation during the acute phase of acute myocardial infarction on in-hospital and 5-year mortality rates in the percutaneous coronary intervention era

.

Circ J

2016

;

80

(

7

):

1539

–

1547

.

459

Haissaguerre

M

,

Vigmond

E

,

Stuyvers

B

,

Hocini

M

,

Bernus

O.

Ventricular arrhythmias and the His-Purkinje system

.

Nat Rev Cardiol

2016

;

13

(

3

):

155

–

166

.

460

Enjoji

Y

,

Mizobuchi

M

,

Muranishi

H

,

Miyamoto

C

,

Utsunomiya

M

,

Funatsu

A

,

Kobayashi

T

,

Nakamura

S.

Catheter ablation of fatal ventricular tachyarrhythmias storm in acute coronary syndrome—role of Purkinje fiber network

.

J Interv Card Electrophysiol

2009

;

26

(

3

):

207

–

215

.

461

Peichl

P

,

Cihak

R

,

Kozeluhova

M

,

Wichterle

D

,

Vancura

V

,

Kautzner

J.

Catheter ablation of arrhythmic storm triggered by monomorphic ectopic beats in patients with coronary artery disease

.

J Interv Card Electrophysiol

2010

;

27

(

1

):

51

–

59

.

462

Nademanee

K

,

Taylor

R

,

Bailey

WE

,

Rieders

DE

,

Kosar

EM.

Treating electrical storm : sympathetic blockade versus advanced cardiac life support-guided therapy

.

Circulation

2000

;

102

(

7

):

742

–

747

.

463

Miwa

Y

,

Ikeda

T

,

Mera

H

,

Miyakoshi

M

,

Hoshida

K

,

Yanagisawa

R

,

Ishiguro

H

,

Tsukada

T

,

Abe

A

,

Yusu

S

,

Yoshino

H.

Effects of landiolol, an ultra-short-acting beta1-selective blocker, on electrical storm refractory to class III antiarrhythmic drugs

.

Circ J

2010

;

74

(

5

):

856

–

863

.

464

Hine

LK

,

Laird

N

,

Hewitt

P

,

Chalmers

TC.

Meta-analytic evidence against prophylactic use of lidocaine in acute myocardial infarction

.

Arch Intern Med

1989

;

149

(

12

):

2694

–

2698

.

465

Huikuri

HV

,

Castellanos

A

,

Myerburg

RJ.

Sudden death due to cardiac arrhythmias

.

N Engl J Med

2001

;

345

(

20

):

1473

–

1482

.

466

Moss

AJ

,

Zareba

W

,

Hall

WJ

,

Klein

H

,

Wilber

DJ

,

Cannom

DS

,

Daubert

JP

,

Higgins

SL

,

Brown

MW

,

Andrews

ML

,

Multicenter Automatic Defibrillator Implantation Trial II Investigators

.

Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction

.

N Engl J Med

2002

;

346

(

12

):

877

–

883

.

467

Bardy

GH

,

Lee

KL

,

Mark

DB

,

Poole

JE

,

Packer

DL

,

Boineau

R

,

Domanski

M

,

Troutman

C

,

Anderson

J

,

Johnson

G

,

McNulty

SE

,

Clapp-Channing

N

,

Davidson-Ray

LD

,

Fraulo

ES

,

Fishbein

DP

,

Luceri

RM

,

Ip

JH

,

Sudden Cardiac Death in Heart Failure Trial Investigators

.

Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure

.

N Engl J Med

2005

;

352

(

3

):

225

–

237

.

468

Chen

A

,

Ashburn

MA.

Cardiac effects of opioid therapy

.

Pain Med

2015

;

16

(Suppl 1)

:

S27

–

31

.

469

Brignole

M

,

Auricchio

A

,

Baron-Esquivias

G

,

Bordachar

P

,

Boriani

G

,

Breithardt

OA

,

Cleland

J

,

Deharo

JC

,

Delgado

V

,

Elliott

PM

,

Gorenek

B

,

Israel

CW

,

Leclercq

C

,

Linde

C

,

Mont

L

,

Padeletti

L

,

Sutton

R

,

Vardas

PE.

2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. The Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA)

.

Eur Heart J

2013

;

34

(

29

):

2281

–

2329

.

470

Caforio

AL

,

Pankuweit

S

,

Arbustini

E

,

Basso

C

,

Gimeno-Blanes

J

,

Felix

SB

,

Fu

M

,

Helio

T

,

Heymans

S

,

Jahns

R

,

Klingel

K

,

Linhart

A

,

Maisch

B

,

McKenna

W

,

Mogensen

J

,

Pinto

YM

,

Ristic

A

,

Schultheiss

HP

,

Seggewiss

H

,

Tavazzi

L

,

Thiene

G

,

Yilmaz

A

,

Charron

P

,

Elliott

PM

,

European Society of Cardiology Working Group on Myocardial and Pericardial Diseases

.

Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases

.

Eur Heart J

2013

;

34

(

33

):

2636

–

48

, 2648a–2648d.

471

Emrich

T

,

Emrich

K

,

Abegunewardene

N

,

Oberholzer

K

,

Dueber

C

,

Muenzel

T

,

Kreitner

KF.

Cardiac MR enables diagnosis in 90% of patients with acute chest pain, elevated biomarkers and unobstructed coronary arteries

.

Br J Radiol

2015

;

88

(

1049

):

20150025

.

472

Pathik

B

,

Raman

B

,

Mohd Amin

NH

,

Mahadavan

D

,

Rajendran

S

,

McGavigan

AD

,

Grover

S

,

Smith

E

,

Mazhar

J

,

Bridgman

C

,

Ganesan

AN

,

Selvanayagam

JB.

Troponin-positive chest pain with unobstructed coronary arteries: incremental diagnostic value of cardiovascular magnetic resonance imaging

.

Eur Heart J Cardiovasc Imaging

2016

;

17

(

10

):

1146

–

1152

.

473

Dastidar

AG

,

Rodrigues

JC

,

Johnson

TW

,

De Garate

E

,

Singhal

P

,

Baritussio

A

,

Scatteia

A

,

Strange

J

,

Nightingale

AK

,

Angelini

GD

,

Baumbach

A

,

Delgado

V

,

Bucciarelli-Ducci

C.

Myocardial Infarction with nonobstructed coronary arteries: impact of CMR early after presentation

.

JACC Cardiovasc Imaging

;doi: 10.1016/j.jcmg.2016.11.010. Published online ahead of print 18 January 2017.

474

Fox

KA

,

Goodman

SG

,

Klein

W

,

Brieger

D

,

Steg

PG

,

Dabbous

O

,

Avezum

A.

Management of acute coronary syndromes. Variations in practice and outcome; findings from the Global Registry of Acute Coronary Events (GRACE)

.

Eur Heart J

2002

;

23

(

15

):

1177

–

1189

.

475

Lenfant

C.

Shattuck lecture - clinical research to clinical practice - lost in translation?

N Engl J Med

2003

;

349

(

9

):

868

–

874

.

476

Schiele

F

,

Gale

CP

,

Bonnefoy

E

,

Capuano

F

,

Claeys

MJ

,

Danchin

N

,

Fox

KA

,

Huber

K

,

Iakobishvili

Z

,

Lettino

M

,

Quinn

T

,

Rubini Gimenez

M

,

Botker

HE

,

Swahn

E

,

Timmis

A

,

Tubaro

M

,

Vrints

C

,

Walker

D

,

Zahger

D

,

Zeymer

U

,

Bueno

H.

Quality indicators for acute myocardial infarction: A position paper of the Acute Cardiovascular Care Association

.

Eur Heart J Acute Cardiovasc Care

2017

;

6

(

1

):

34

–

59

.

477

Ford

I

,

Norrie

J.

Pragmatic trials

.

N Engl J Med

2016

;

375

(

5

):

454

–

463

.

Author notes

*

ESC Committee for Practice Guidelines (CPG) and National Cardiac Societies document reviewers: listed in the Appendix.

*

ESC entities having participated in the development of this document: Associations: Acute Cardiovascular Care Association (ACCA), European Association of Preventive Cardiology (EAPC), European Association of Cardiovascular Imaging (EACVI), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Heart Rhythm Association (EHRA), Heart Failure Association (HFA). Councils: Council on Cardiovascular Nursing and Allied Professions (CCNAP), Council for Cardiology Practice (CCP). Working Groups: Cardiovascular Pharmacotherapy, Cardiovascular Surgery, Coronary Pathophysiology and Microcirculation, Myocardial and Pericardial Diseases, Thrombosis.

*

The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC (journals.permissions@oxfordjournals.org).

*

Disclaimer. The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication. The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver. Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

© The European Society of Cardiology 2017. All rights reserved. For permissions please email: journals.permissions@oxfordjournals.org.

Supplementary data

Comments

1 Comment

Reducing door-to-balloon time: how can we further improve?

30 November 2017

Giuseppe Biondi-Zoccai

Sapienza University of Rome

Primary percutaneous coronary intervention (PPCI) is currently the preferred treatment for acute ST-segment elevation myocardial infarction (STEMI). Previous studies have shown a strong association between the time elapsing from the patient's arrival at the emergency department to the balloon-mediated restoration of valid antegrade flow (door-to-balloon time) and the mortality rate (1-5). On the basis of these results, current American and European clinical consensus document and guidelines endorse a door-to-balloon time of 90 minutes or less as the target, giving it the highest recommendation level (6,7). Therefore, this time and the percentage of patients for whom the door-to-balloon time is 90 minutes or less has become the target of all quality-improvement initiatives for acute cardiac care and have evolved as key quality metrics for benchmarking and comparative purposes. Nevertheless, in many cases door-to-balloon time is longer than the 90-minutes (8).
Delay can occur in several steps of the course between patient arrival to the emergency department and balloon inflation in the catheterization laboratory, including time to obtain an electrocardiogram (ECG), time from ECG to diagnosis of STEMI, time to patient transfer from emergency department to the catheterization laboratory, and time to open the infarct-related artery with PPCI (9-12). Although variation in this complex process is inevitable, some delays may be avoided though process redesign and novel strategies. In particular, we explicitly advocate that hospitals identified as hub centers for PPCI require catheterization laboratory staff and interventional cardiologists being always present (24/7) in the hospital, ready to start treatment for a STEMI patient in a timely matter, thus abolishing any delay related to reaching for personnel at home and awaiting their arrival to the hospital.
This strategy is important in particular when patient arrive in the emergency department without a clear-cut pre-hospital diagnosis. In such a scenario, when the emergency department receives notice of a suspected STEMI patient, the emergency department calls the hospital operator, who immediately pages both the on-call catheterization laboratory staff and the on-call interventional cardiologist. The catheterization laboratory staff and the interventional cardiologist are expected to be ready to start the procedure within 30 minutes of receiving the page. This important delay could be avoided by catheterization laboratory staff and interventional cardiologists always present (24/7) in the hospital. Furthermore, with this kind of organization the cardiologist performing the procedure is immediately involved in the treatment process, having the opportunity to know the complexity of the clinical status before transferring the patient to the catheterization room and being personally involved in the activation of PPCI procedure. Other benefits include the early involvement of other key consultants in complex cases (e.g. cardiac surgeons, vascular surgeons), as well as the ad hoc preparation of procedures and devices for circulatory support (e.g. left ventricular assist devices).
Our proposal has already been successfully implemented in the recent past at Tor Vergata University Hospital in Rome, Italy, with evident benefits. Indeed, the results obtained implementing in a systematic fashion this strategy have led to a significant reduction of door-to-balloon time and subsequent morbidity, hospital stay and mortality rate (from 89 to 49 minutes and from 8.9% to 3.9%, respectively [both p<0.05]). In particular, reductions in door-to-balloon time may have no effect on infarct size when total ischemic time is long, but may have important consequences when the total ischemic time is short. This organization appears very important and beneficial for hospitals that are involved as hub in the network of STEMI, in particular in a metropolitan area.
In conclusion, the modern approach to the treatment of STEMI could introduce new care models, including immediate on site availability of all interventional cardiology personnel. The effort to reduce total ischemic time should remain a top priority in the fight to reduce the medical and social effects of STEMI.

Francesco Versaci, MD, FACC
Division of Cardiology, S. Maria Goretti Hospital, Latina, Italy

Giuseppe Biondi-Zoccai, MD, MStat
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy

Francesco Romeo, MD, FESC, FACC
Division of Cardiology, Tor Vergata University, Rome, Italy

1. Menees DS, Peterson ED, Wang Y, Curtis JP, Messenger JC, Rumsfeld JS, Gurm HS. Door-to-balloon time and mortality among patients undergoing primary PCI. N Engl J Med 2013 Sep 5;369:901-9.

2. Shahin M, Obeid S, Hamed L, Templin C, Gamperli O, Nietlispach F, Maier W, Yousif N, Mach F, Roffi M, Windecker S, Raber L, Matter CM, Luscher TF. Occurrence and Impact of Time Delay to Primary Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction. Cardiol Res 2017;8:190-198.

3. Yudi MB, Ramchand J, Farouque O, Andrianopoulos N, Chan W, Duffy SJ, Lefkovits J, Brennan A, Spencer R, Fernando D, Hiew C, Freeman M, Reid CM, Ajani AE, Clark DJ; Melbourne Interventional Group. Impact of door-to-balloon time on long-term mortality in high- and low-risk patients with ST-elevation myocardial infarction. Int J Cardiol 2016;224:72-78.

4. Varcoe RW, Clayton TC, Gray HH, de Belder MA, Ludman PF, Henderson RA; British Cardiovascular Intervention Society (BCIS) and the National Institute for Cardiovascular Outcomes Research (NICOR). Impact of call-to-balloon time on 30-day mortality in contemporary practice. Heart 2017;103:117-124.

5. Sardar MR, Dawn Abbott J. Myocardial salvage and mortality in STEMI: A race against ischemic time. Catheter Cardiovasc Interv 2016;87:1201-2.

6. Terkelsen CJ, Sorensen JT, Maeng M, Jensen LO, Tilsted HH, Trautner S, Vach W, Johnsen SP, Thuesen L, Lassen JF. System delay and mortality among patients with STEMI treated with primary percutaneous coronary intervention. JAMA 2010;304:763–771.

7. Fordyce CB, Al-Khalidi HR, Jollis JG, Roettig ML, Gu J, Bagai A, Berger PB, Corbett CC, Dauerman HL, Fox K, Garvey JL, Henry TD, Rokos IC, Sherwood, MW, Wilson BH, Granger CB, STEMI Systems Accelerator Project. Association of rapid care process implementation on reperfusion times across multiple STsegment- elevation myocardial infarction networks. Circ Cardiovasc Interv 2017;10:e004061.

8. Stowens JC, Sonnad SS, Rosenbaum RA. Using EMS dispatch to trigger STEMI alerts decreases door-to-balloon times. West J Emerg Med 2015;16(3):472–480. Squire BT, Tamayo-Sarver JH, Rashi P, Koenig W, Niemann JT. Effect of prehospital cardiac catheterization lab activation on door-to-balloon time, mortality, and false-positive activation. Prehosp Emerg Care 2014;18:1-8.

9. Nallamothu BK, Normand SL, Wang Y, Hofer TP, Brush JE, Jr, Messenger JC, Bradley EH, Rumsfeld JS, Krumholz HM. Relation between door-to-balloon times and mortality after primary percutaneous coronary intervention over time: a retrospective study. Lancet 2015;385:1114–1122.

10. Bagai A, Jollis JG, Dauerman HL, Peng SA, Rokos IC, Bates ER, French WJ, Granger CB, Roe MT. Emergency department bypass for ST-segment-elevation myocardial infarction patients identified with a prehospital electrocardiogram: a report from the American Heart Association Mission: Lifeline program. Circulation 2013;128:352–359.

11. Wang TY, Nallamothu BK, Krumholz HM, Li S, Roe MT, Jollis JG, Jacobs AK, Holmes DR, Peterson ED, Ting HH. Association of door-in to door-out time with reperfusion delays and outcomes among patients transferred for primary percutaneous coronary intervention. JAMA 2011;305:2540–2547.

12. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2017 Aug 26. [Epub ahead of print].

Submitted on 30/11/2017 11:46 AM GMT

Tracking Number Ri 26 406 315 9 Bg

Source: https://academic.oup.com/eurheartj/article/39/2/119/4095042

Share this post