European Heart Journal (2012) 33, 25692619 ESC GUIDELINES

doi:10.1093/eurheartj/ehs215

ESCGuidelinesforthemanagementofacute
myocardialinfarctioninpatientspresenting
withST-segmentelevation
The Task Force on the management of ST-segment elevation acute
myocardial infarction of the European Society of Cardiology (ESC)
Authors/Task Force Members: Ph. Gabriel Steg (Chairperson) (France)*,
Stefan K. James (Chairperson) (Sweden)*, Dan Atar (Norway), Luigi P. Badano
(Italy), Carina Blomstrom-Lundqvist(Sweden), Michael A. Borger (Germany),
Carlo Di Mario (United Kingdom), Kenneth Dickstein (Norway), Gregory Ducrocq
(France), Francisco Fernandez-Aviles (Spain), Anthony H. Gershlick (United
Kingdom), Pantaleo Giannuzzi(Italy), Sigrun Halvorsen (Norway), Kurt Huber
(Austria), Peter Juni(Switzerland), Adnan Kastrati(Germany), Juhani Knuuti
(Finland), Mattie J. Lenzen (Netherlands), Kenneth W. Mahaffey (USA),
Marco Valgimigli(Italy), Arnoud van t Hof (Netherlands), Petr Widimsky
(Czech Republic), Doron Zahger (Israel)
ESC Committee for Practice Guidelines (CPG): Jeroen J. Bax (Chairman) (Netherlands), Helmut Baumgartner
(Germany), Claudio Ceconi (Italy), Veronica Dean (France), Christi Deaton (UK), Robert Fagard (Belgium),
Christian Funck-Brentano (France), David Hasdai (Israel), Arno Hoes (Netherlands), Paulus Kirchhof
(Germany UK), Juhani Knuuti (Finland), Philippe Kolh (Belgium), Theresa McDonagh (UK), Cyril Moulin (France),
Bogdan A. Popescu (Romania), Z eljko Reiner (Croatia), Udo Sechtem (Germany), Per Anton Sirnes (Norway),
Michal Tendera (Poland), Adam Torbicki (Poland), Alec Vahanian (France), Stephan Windecker (Switzerland).
Document Reviewers: David Hasdai (CPG Review Coordinator) (Israel), Felicity Astin (UK), Karin A stro m-Olsson
(Sweden), Andrzej Budaj (Poland), Peter Clemmensen (Denmark), Jean-Philippe Collet (France), Keith A. Fox
(UK), AhmetFuat (UK), OlivijaGustiene (Lithuania), Christian W.Hamm (Germany), PetrKala (Czech Replublic),
Patrizio Lancellotti (Belgium), Aldo Pietro Maggioni (Italy), Be la Merkely (Hungary), Franz-Josef Neumann
(Germany), Massimo F. Piepoli (Italy), Frans Van de Werf (Belgium), Freek Verheugt (Netherlands),
Lars Wallentin (Sweden)

*Corresponding authors: Ph. Gabriel Steg (Chairperson), AP-HP, Ho pital Bichat / Univ Paris Diderot, Sorbonne Paris-Cite / INSERM U-698, Paris, France. Tel: +33
1 40 25 86 68,
Fax: +33
Other ESC1 entities
40 25 88having
65, Email: gabriel.steg@bch.aphp.fr
participated in the development of this document:
Associations: European Association of Echocardiography (EAE), European Association for Cardiovascular Prevention (EACPR), European Heart Rhythm Association
(EHRA), Euro-
pean Association of Percutaneous Cardiovascular Interventions (EAPCI), Heart Failure Association (HFA)
Working Groups: Acute Cardiac care, Cardiovascular Pharmacology and Drug Therapy, Thrombosis
Councils: Cardiovascular Imaging, Cardiovascular Nursing and Allied Professions, Primary Cardiovascular Care, Cardiovascular Surgery
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
Stefan K. James
University Press,(Chairperson), Department
the publisher of of Medical
the European Sciences
Heart Journal and/ Uppsala
the partyClinical Research
authorized Center,
to handle Uppsala
such University
permissions and Department
on behalf of the ESC. of Cardiology Uppsala
University Hospital,
75185 Uppsala,
Disclaimer. Sweden.
The ESC Tel: +46
Guidelines 705 944the
represent 404, Fax:of
views +46
the18 506
ESC and638, Email:
were Stefan.james@ucr.uu.se
arrived at after careful consideration of the available evidence at the time they were
written. Health
professionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override the individual
responsibility of health
professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and
necessary the patients
guardian or carer. It is also the health professionals responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.
& The European Society of Cardiology 2012. All rights reserved. For permissions please email: journals.permissions@oup.com
 2570 ESC Guidelines

The disclosure forms of the authors and reviewers are available on the ESC website www.escardio.org/guidelines

Online publish-ahead-of-print 24 August 2012

-----------------------------------------------------------------------------------------------------------------------
-------------------------------
Keywords Guidelines Acute myocardial infarction ST-segment elevation Acute coronary syndromes
Ischaemic heart disease Reperfusion therapy Primary percutaneous coronary intervention
Antithrombotic therapy Secondary prevention
4.4.7. Angiotensin-converting enzyme inhibitors and
angiotensin receptor blockers . . . . . . . . . . . . . . . . . .2598
4.4.8. Aldosterone antagonists . . . . . . . . . . . . . . . . . .2598
4.4.9. Magnesium, glucoseinsulinpotassium, lidocaine .2598
Table of Contents 5. Complications following ST-segment elevation myocardial
infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2600
5.1. Haemodynamic disturbances . . . . . . . . . . . . . . . . . .2600
Abbreviations and Acronyms . . . . . . . 5.1.1. . . . . . Heart
. . . . .failure.
. . . . . .2570
. . . . . . . . . . . . . . . . . . . . . . . . .2600
1. Preamble. . . . . . . . . . . . . . . . . . . . .5.1.2.
. . . . .Management
. . . . . . . . .2572 of heart failure following ST-segment
2. Introduction. . . . . . . . . . . . . . . . . . .elevation
. . . . . . . myocardial
. . . . . . .2573 infarction (Table 23) . . . . . . . . . . .2601
2.1. Denition of acute myocardial infarction . . . . . . . . .and
5.1.3. Arrhythmias .2573 conduction disturbances in the
2.2. Epidemiology of ST-segment elevation acute phase myocardial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2603
infarction . . . . . . . . . . . . . . . . . . . .5.2.
. . . Cardiac
. . . . . . .complications
. . . .2573 . . . . . . . . . . . . . . . . . . . . . .2606
3. Emergency care . . . . . . . . . . . . . . .5.2.1. . . . . .Mitral
. . . . .valve
. . . . .2574
regurgitation . . . . . . . . . . . . . . . . .2606
3.1. Initial diagnosis . . . . . . . . . . . . 5.2.2.. . . . . Cardiac
. . . . . . .rupture
. . .2574 . . . . . . . . . . . . . . . . . . . . . . .2607
3.2. Relief of pain, breathlessness and 5.2.3. Ventricular. .septal
anxiety . . . . . . . .2576
rupture . . . . . . . . . . . . . . . . .2607
3.3. Cardiac arrest . . . . . . . . . . . . . .5.2.4. . . . . .Right
. . . . ventricular
. . . .2576 infarction . . . . . . . . . . . . . . . .2607
3.4. Pre-hospital logistics of care . . .5.2.5. . . . . .Pericarditis
. . . . . . . . .. .2577
. . . . . . . . . . . . . . . . . . . . . . . . . .2607
3.4.1. Delays . . . . . . . . . . . . . . . . .5.2.6.
. . . . .Left
. . . ventricular
. . . . .2577 aneurysm . . . . . . . . . . . . . . . . .2607
3.4.2. Emergency medical system 5.2.7. . . . . . Left
. . . .ventricular
. . . . . . .2578 thrombus . . . . . . . . . . . . . . . . .2607
3.4.3. Networks . . . . . . . . . . . . 6. . . Gaps
. . . . .in. .the. . .evidence
. . .2578 and areas for future research . . . . . . .2608
3.4.4. General practitioners . . . . . . . . . . . . . . . . . . . .2579
3.4.5. Admission procedures . . . . . . . . . . . . . . . . . . .2579
3.4.6. Logistics . . . . . . . . . . . . . . . . . . . . . . . . . . . .2579
3.5. Reperfusion therapy . . . . . . . . . . . . . . . . . . . . . . .2580
3.5.1. Restoring coronary ow and myocardial tissue
Abbreviations and Acronyms
reperfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2580
3.5.2. Selection of a strategy for reperfusion . . . . . . . . .2581
3.5.3. Primary percutaneous coronary intervention . . . .2582
3.5.4. Fibrinolysis and subsequent interventions . . . . . . .2586
3.5.5. Coronary bypass surgeryACE and multivessel angiotensin-converting
coronary enzyme
revascularization . . . . . . . . . . . ACS . . . . . . . . . . acute coronary syndrome
. . . . . .2590
3.5.6. Non-reperfused patients ADP . . . . . . . . . . .adenosine
. . . . . . .2590 diphosphate
3.6. Management of hyperglycaemia AF in the acute atrialphase of ST-
brillation
segment elevation myocardial infarction. AMI . . . .acute
. . . . . myocardial
. . . .2592 infarction
4. Management during hospitalization and at discharge . . . . . .2593
AV atrioventricular
4.1. Coronary care unit logistics and monitoring . . . . . . . .2593
4.1.1. Coronary care unit . . . . .AIDA-4 . . . . . . . . . . . .Abciximab
. . . .2593 Intracoronary vs. intravenously
4.1.2. Monitoring . . . . . . . . . . . . . . . . . . . . Drug . . . . .Application
. .2593
4.1.3. Ambulation . . . . . . . . . . .APACHE . . . . . . . II. . . . . Acute
. . .2593 Physiology Aand Chronic Health Evalu-
4.1.4. Length of stay. . . . . . . . . . . . . . . . . .ation . . . . .II. .2593
4.2. Risk assessment and imaging ATOLL. . . . . . . . . .Acute. . . . . myocardial
. . .2594 infarction Treated with
4.2.1. Indications and timing . . . . . . . . . . .primary . . . . . . . angioplasty
. .2594 and inTravenous enOxa-
4.3. Assessment of myocardial viability . . . .parin . . . . .or . . unfractionated
. . .2595 heparin to Lower is-
4.4. Long-term therapies for ST-segment elevation chaemic and bleeding events at short- and
myocardial infarction . . . . . . . . . . . . . . . . . . . . . . . . . .2595
Long-term follow-upAcute Myocardial Infarc-
4.4.1. Lifestyle interventions and risk factor control . . . .2595
4.4.2. Antithrombotic therapy . . . . . . . . . . tion . . . . Treated
. . . .2596 with Primary Angioplasty and
4.4.3. Beta-blockers . . . . . . . . . . . . . . . . . . . . . . . . .2597Enoxaparin or Unfractionated
Intravenous
4.4.4. Lipid-lowering therapy . . . . . . . . . . .Heparin . . . . . . . to.2598 Lower Ischemic and Bleeding
4.4.5. Nitrates . . . . . . . . . . . . . . . . . . . . . . Events at Short- and Long-term Follow-up
. . . . . . .2598
4.4.6. Calcium antagonists . . . . . . . . . . . . . . . . . . . . .2598
ESC Guidelines 2571

aPTT activated partial thromboplastin time GRACIA GRupo de Ana alisis

Isque de-la Cardiopat1
ARB angiotensin receptor blocker mica Aguda
ASSENT 3 ASssessment of the Safety and Efcacy of aGUSTO Global Utilization of Streptokinase and Tissue
New Thrombolytic 3 plasminogen activator for Occluded coronary
ATLAS ACS (etc.) Anti-Xa Therapy to Lower cardiovascular arteries
events in Addition to Standard therapy in sub- HbA1c haemoglobin A1c
jects with Acute Coronary Syndrome HORIZONSAMI Harmonizing Outcomes with RevascularIZa-
Thrombolysis In Myocardial Infarction 51 tiON and Stents in Acute Myocardial
b.i.d. bis in die (twice daily) Infarction
BMI body mass index i.c. intracoronary
BMS bare-metal stent i.v. intravenous
BNP B-type natriuretic peptide IABP intra-aortic balloon pump
BRAVE-3 Bavarian Reperfusion Alternatives INFUSEAMI Intracoronary abciximab iNFUsion and aspir-
Evaluation-3 ation thrombectomy for anterior ST-segment
CAD coronary artery disease ElevAtion Myocardial Infarction
CAPITAL-AMI Combined Angioplasty and Pharmacological IRA infarct-related artery
Intervention vs. Thrombolytics ALlone in ISIS-2 Second International Study of Infarct Survival
Acute Myocardial Infarction Lab catheterization laboratory
CHA2DS2-VASc Cardiac failure, Hypertension, Age e75 LBBB left bundle branch block
[Doubled], Diabetes, Stroke [Doubled] LDL low-density lipoprotein
VASascular disease, Age 6574 and Sex cat- LV left ventricular
egory [Female]) LVAD left ventricular assist device
CHADS2 Cardiac failure, Hypertension, Age, Diabetes,
NORDISTEMI NORwegian study on DIstrict treatment of
Stroke (Doubled) ST-Elevation Myocardial Infarction
CK-MB creatine kinase myocardial band NRMI National Registry of Myocardial Infarction
CLARITY-TIMI 28 NSTE-ACS non-ST-segment elevation acute coronary
28 syndromes
OASIS Optimal Antiplatelet Strategy for
CLlopidogrel as Adjunctive Reperfusion InterventionS
TherapyThrombolysis Iin Myocardial Infarc- OAT Occluded Artery Trial
tion 28 ON-TIME 2 ONgoing Tiroban In Myocardial infarction
COMMIT Clopidogrel and Metoprolol in Myocardial In- Evaluation
farction Trial OPTIMAAL OPtimal Therapy In Myocardial infarction
CPG Committee for Practice Guidelines with the Angiotensin II Antagonist Losartan
CRISP AMI Counterpulsation to Reduce Infarct Size p.o. per os
Pre-PCI-Acute Myocardial Infarction PAMI-II Primary Angioplasty in Myocardial Infarction II
CRT cardiac resynchronization therapy PET positron emission tomography
CVLPRIT Complete Versus Lesion-only PRIimary PCI PCI percutaneous coronary intervention
Trial PLATO PLATelet inhibition and patient Outcomes
CT computed tomography PRAMI PReventive Angioplasty in Myocardial Infarc-
DAPT dual antiplatelet therapy tion trial
DES drug-eluting stent PRIMARY PCI primary percutaneous coronary intervention
DIGAMI Diabetes, Insulin Glucose Infusion in Acute PROVE IT-TIMI 22 PRavastatin Or atorVastatin Evaluation and
Myocardial Infarction In-
EAPCI European Association of Percutaneous Car- fection TherapyThrombolysis In Myocardial
diovascular Interventions Infarction 22
ECG electrocardiogram RBBB right bundle branch block
EMS emergency medical system r-PA reteplase
EPHESUS Eplerenone Post-AMI Heart failure Efcacy RIFLE-STEACS RadIal Vs. FemoraL randomized investigation
and SUrvival Study in ST elevation Acute Coronary Syndrome
ESC European Society of Cardiology RIVAL RadIal Vs. femorAL access for coronary
ExTRACT-TIMI 25 Enoxaparin and Thrombolysis Reperfusion for intervention
ACute myocardial infarction Treatment SBP systolic blood pressure
Thrombolysis In Myocardial Infarction 25 SHOCK SHould we emergently revascularize
FINESSE Facilitated INtervention with Enhanced reper- Occluded coronaries for Cardiogenic
fusion Speed to Stop Events shocK
FMC rst medical contact
GP glycoprotein
 2572 ESC Guidelines

STEMI substitutes but are complements for textbooks and cover the
ST-segment elevation myocardial infarction
STREAM ESC Core Curriculum topics. Guidelines and recommendations
STrategic Reperfusion Early After Myocardial
infarction should help physicians to make decisions in their daily practice.
t-PA tissue plasminogen activator However, the nal decisions concerning an individual patient
TACTICS must be made by the responsible physician(s).
Treat angina with Aggrastat and determine
Cost of Therapy with an Invasive or Conser- A great number of guidelines have been issued in recent years by
vative Strategy the European Society of Cardiology (ESC), as well as by other so-
TAPAS Thrombus Aspiration during Percutaneouscieties and organizations. Because of their impact on clinical prac-
coronary intervention in Acute myocardial tice, quality criteria for the development of guidelines have been
infarction established, in order to make all decisions transparent to the
TIA transient ischaemic attack user. The recommendations for formulating and issuing ESC guide-
TNK-tPA tenecteplase lines can be found on the ESC web site (http://www.escardio.org/
TRANSFER guidelines-surveys/esc-guidelines/about/Pages/rules-writing.aspx).
Trial of Routine ANgioplasty and Stenting
after Fibrinolysis to Enhance Reperfusion ESCin guidelines represent the ofcial position of the ESC on a given
acute myocardial infarction topic and are regularly updated.
TRITONTIMI 38 TRial to assess Improvement in Therapeutic of this Task Force were selected by the ESC to repre-
Members
Outcomes by optimizing platelet InhibitioNsent professionals involved with the medical care of patients with
with prasugrelThrombolysis in Myocardial this condition. Selected experts in the eld undertook a compre-
Infarction 38 hensive review of the published evidence for diagnosis, manage-
UFH unfractionated heparin ment and/or prevention of a given condition, according to ESC
VALIANT Committee for Practice Guidelines (CPG) policy. A critical evalu-
VALsartan In Acute myocardial iNfarction
Trial ation of diagnostic and therapeutic procedures was performed, in-
VF ventricular brillation cluding assessment of the riskbenet ratio. Estimates of expected
VT ventricular tachycardia health outcomes for larger populations were included, where data
exist. The levels of evidence and the strengths of recommendation
of particular treatment options were weighed and graded
according to predened scales, as outlined in Tables 1 and 2.
1.Preamble The experts of the writing and reviewing panels lled in Declar-
ation of Interest forms, in order to identify what might be per-
ceived as real
Guidelines summarize and evaluate all available evidenceat theor potential sources of conicts of interest. These
time of the writing processon a particular issue, with the aim compiled into a single le and can be found on the
forms were
ESC web strategies
of assisting physicians in selecting the best management site (http://www.escardio.org/guidelines). Any changes
in declarations
for an individual patient with a given condition, taking into of interest that arise during the writing period
account the impact on outcome, as well as the riskbenet ratio to the ESC and updated. The Task Force received
must be notied
of particular diagnostic or therapeutic means. Guidelines are not

Table 1 Classes of recommendations

Classes of
recommendations Denition Suggested wording to use

Is recommended/is
Class I Evidence and/or general agreement
indicated
that a given treatment or procedure
is benecial, useful, effective.

Class II Conicting evidence and/or a

divergence of opinion about the
usefulness/efcacy of the given
treatment or procedure.
Class IIa Should be considered
Weight of evidence/opinion is in
favour of usefulness/efcacy.
May be considered
Class IIb Usefulness/efcacy is less well
established by evidence/opinion.
Is not
Class III Evidence or general agreement thatrecommended
the given treatment or procedure
is not useful/effective, and in some
cases may be harmful.
ESC Guidelines 2573

Table 2 Levels of evidence Table 3 Universal denition of myocardial infarction a

Level Data derived from multiple Detection of rise and/or fall of cardiac biomarker values
of
randomized (preferably
evidenc
clinical trials or meta-analyses. troponin) with at least one value above the 99th
eA Data derived from a single percentile of the upper
randomized reference limit and with at least one of the following:
Level of
clinical trial or large non-
evidence B Symptoms of ischaemia;
randomized New or presumably new signicant ST-T changes or new
Consensus of opinion of the
studies.
experts and/ LBBB;
or small studies, retrospective Development of pathological Q waves in the ECG;
Level of studies, Imaging evidence of new loss of viable myocardium,
evidence Cregistries. orautopsy.
new
regional
Cardiac wallwith
death motion abnormality;
symptoms suggestive of
Identication of an
myocardial ischaemia,intracoronary thrombus by
angiography or
and presumably new ECG changes or new LBBB, but
its entire nancial support from the ESC, without any involvement
death occurring
from the healthcare industry. before blood cardiac biomarkers values are released
The ESC CPG supervises and co-ordinates the preparation ofor before cardiac
new guidelines produced by task forces, expert groups or consen- biomarker values would be increased.
sus panels. The Committee is also responsible for the endorse- Stent thrombosis associated with MI when detected
ment process of these Guidelines. The ESC Guidelines undergo by coronary
extensive review by the CPG and external experts. After appropri- angiography or autopsy in the setting of myocardial
ECG electrocardiogram; LBBB left bundle branch block.
ate revisions, it is approved by all the experts involved in the ischaemia and with
Task myocardial
aExcluding infarction associated with revascularization
Force. The nalized document is approved by the CPG for publi- a rise and/or
procedures or fall of cardiac biomarker values with at
leastfor
criteria one value
prior myocardial infarction.
cation in the European Heart Journal.
above the 99th percentile URL.
The task of developing ESC Guidelines covers not only the
integration of the most recent research, but also the thecreation of
great number of trials on new treatments performed in recent
educational tools and implementation programmesyears, for the recom-
and in view of new diagnostic tests, the ESC decided that it
mendations. To implement the guidelines, condensed waspocket guide-
opportune to upgrade the previous guidelines and appointed
lineseditions,summaryslides,bookletswithessentialmessages,and
aTaskForce.Itmustberecognizedthat,evenwhenexcellentclinical
electronic versions for digital applications (smartphones, etc.)been
trials have are undertaken, their results are open to interpretation
produced. These versions are abridged and, thus, ifand needed, one
that treatment options may be limited by resources. Indeed,
should always refer to the full text version, which iscost-effectiveness
freely available is becoming an increasingly important issue
on the ESC web site. The national societies of the ESCwhen are encour-upon therapeutic strategies.
deciding
aged to endorse, translate and implement the ESC Guidelines.
Owing to major changes in the biomarkers available for diagno-
Implementation programmes are needed because sis, it has been for acute myocardial infarction have been revised. The
criteria
shown that the outcome of disease may be favourably inuenced
current international consensus denition states that the term
by the thorough application of clinical recommendations.
acute myocardial infarction (AMI) should be used when there is
Surveys and registries are needed to verify that real-life
evidence daily
of myocardial necrosis in a clinical setting consistent
practice is in keeping with what is recommended inwith the myocardial
guidelines, ischaemia.2 Under these conditions, any one of
thus completing the loop between clinical research, writing
the of described in Table 3 meets the diagnosis for spontan-
criteria
guidelines, and implementing them into clinical practice.
eous myocardial infarction. The present guidelines pertain to
The guidelines do not, however, override the individual
patientsrespon-
presenting with ischaemic symptoms and persistent
sibility of health professionals to make appropriateST-segment
decisions elevation on the electrocardiogram (ECG). Most of
according to the circumstances of individual patient, in consultation
these patients will show a typical rise in biomarkers of myocardial
with that patient and, where appropriate and necessary,
necrosistheand progress to Q-wave myocardial infarction. Separate
patients guardian or carer. It is also the health professionals
guidelines have recently been developed by another Task Force
responsibility to verify the rules and regulations applicable
of the ESC to for patients presenting with ischaemic symptoms but
drugs and devices at the time of prescription. without persistent ST-segment elevation and for patients undergo-
ing myocardial revascularization in general.3,4

2.Introduction
2.2Epidemiology of ST-segment
2.1Denition of acute myocardial elevation myocardial infarction
Worldwide, coronary artery disease (CAD) is the single most fre-
infarction quent cause of death. Over seven million people every year die
The management of acute myocardial infarction continues
from CAD, to accounting for 12.8% of all deaths. 5 Every sixth man
undergo major changes. Good practice should be based
and everysound
on seventh woman in Europe will die from myocardial in-
evidence, derived from well-conducted clinical trials. Because
farction. Theofincidence of hospital admissions for AMI with
ST-segment elevations (STEMI) varies among countries that
 2574 ESC Guidelines

belong to the ESC.6 The most comprehensive STEMI registry is

probably in Sweden, where the incidence is 66 STEMI/100 000/ Table 4 Recommendations for initial diagnosis
year. Similar gures were also reported in the Czech Republic, 7
Belgium,6 and the USA: 8 the incidence rates (per 100 000) of Recommendations Class a Level b Ref C
STEMI decreased between 1997 and 2005 from 121 to 77, A 12-lead ECG must be
whereas the incidence rates of non-STEMI increased slightly obtained as soon as possible
I
at the point of FMC, B a 17, 19
with
from 126 to 132. Thus, the incidence of STEMI appears to be de-
target delay of d10 min.
clining, while there is a concomitant increase in the incidence of
non-STEMI.9 The mortality of STEMI is inuenced by many
factors, among them: age, Killip class, time delay to treatment, ECG monitoring must be
initiated as soonI as possible
mode of treatment, history of prior myocardial infarction, diabetes
B 20, 21
in all patients with suspected
mellitus, renal failure, number of diseased coronary arteries, ejec-
tion fraction, and treatment. The in-hospital mortality of unse- STEMI.
lected STEMI patients in the national registries of the ESC Blood sampling for serum
countries varies between 6% and 14%.10 Several recent studies markers is recommended
I
routinely in the acute Cphase-
have highlighted a fall in acute and long-term mortality following
but one should not wait for
STEMI, in parallel with greater use of reperfusion therapy, primary
the results before initiating
percutaneous coronary intervention (primary PCI), modern antith- reperfusion treatment.
rombotictherapyandsecondarypreventiontreatments. 6,8,11,12Still,
mortality remains substantial with approximately 12% of patients The use of additional
deadwithin6months,13butwithhighermortalityratesinhigher-riskposterior chest wall leads
(V7V9 e0.05 mV) in patients IIa C -
patients,14 which justies continuous efforts to improve quality of
with high suspicion of infero-
care, adherence to guidelines and research.
basal myocardial infarction
(circumex occlusion) should
be considered.
Echocardiography may
assist
3.Emergency care in making the
IIb C -
diagnosis in
uncertain cases but
3.1Initial diagnosis should not
Managementincluding both diagnosis and treatmentof AMI delay transfer for
ECG electrocardiogram; FMC rst medical contact; STEMI ST-
starts at the point of rst medical contact (FMC), dened as the angiography.
segment
point at which the patient is either initially assessed by a paramedic
elevation myocardial infarction.
or physician or other medical personnel in the pre-hospital setting,
aClass of recommendation.
bLevel of evidence.
or the patient arrives at the hospital emergency department and
cReference
therefore often in the outpatient setting.15 A working diagnosis of
myocardial infarction must rst be made. This is usually based on a
history of chest pain lasting for 20 min or more, note0.2 mV in men
responding toover the age of 40 years, or e0.15 mV in women
nitroglycerine. Important clues are a history of CAD in leads V2V3 and/or e0.1 mV in other leads (in the absence of
and radiation
of the pain to the neck, lower jaw or left arm. Theleft
painventricular
may not be (LV) hypertrophy or left bundle branch block
(LBBB).2 Insuch
severe. Some patients present with less-typical symptoms, patients
as with inferior myocardial infarction, it is
advisable or
nausea/vomiting, shortness of breath, fatigue, palpitations to record right precordial leads (V3R and V4R) seeking
syncope. These patients tend to present later, areST elevation,
more likely to in order to identify concomitant right ventricular
infarction.
be women, diabetic or elderly patients, and less frequently 2,18 Likewise, ST-segment depression in leads V1V3
suggests
receive reperfusion therapy and other evidence-based therapies myocardial ischaemia, especially when the terminal
T-wave is
than patients with a typical chest pain presentation. Registries positive (ST-elevation equivalent), and may be conrmed
by concomitant
show that up to 30% of patients with STEMI present with atypical ST elevation e0.1 mV recorded in leads V 7V9.2
The
symptoms.16 Awareness of these atypical presentations and a ECG diagnosis may be more difcult in some cases
(Table
liberal access to acute angiography for early diagnosis might5), which nevertheless deserve prompt management.
improve outcomes in this high-risk group. Among these:
Timely diagnosis of STEMI is key to successful management.
ECG monitoring should be initiated as soon as possibleBBB: in the
all presence of LBBB, the ECG diagnosis of acute
myocardial
patients with suspected STEMI to detect life-threatening arrhyth- infarction is difcult, but often possible if marked
ST abnormalities
mias and allow prompt debrillation if indicated. A 12-lead ECG are present. Somewhat complex algorithms
should be obtained and interpreted as soon as possible have atbeentheoffered to assist the diagnosis, 22 but they do not
point of FMC (Table 4).17 Even at an early stage, the provide
ECG isdiagnostic certainty.23 The presence of concordant ST
seldom normal. Typically, ST-segment elevation in elevation
acute myocar- (i.e. in leads with positive QRS deections) appears
to be in
dial infarction, measured at the J point, should be found one twoof con-
the best indicators of ongoing myocardial infarction
tiguous leads and be e0.25 mV in men below the age withofan
40occluded
years, infarct artery.24 Previous data from thromb-
olysis trials have shown that reperfusion therapy is benecial
overall in patients with LBBB and suspected myocardial infarc-
tion. However, most LBBB patients evaluated in the emergency
ESC Guidelines 2575

department do not have an acute coronary occlusion, nor Table do 5 Atypical ECG presentations that deserve
they require primary PCI. A previous ECG may be helpful inprompt de- management in patients with signs and
termining whether the LBBB is new (and, therefore, the suspi- symptoms of ongoing myocardial ischaemia
cion of ongoing myocardial infarction is high). Importantly, in
patients with clinical suspicion of ongoing myocardial ischaemia
with new or presumed new LBBB, reperfusion therapy should " LBBB
be considered promptly, preferably using emergency coronary " Ventricular paced rhythm
angiography with a view to primary PCI or, if unavailable, intra- " Patients without diagnostic ST-segment elevation but with
venous (i.v.) thrombolysis. A positive point-of-care troponinpersistenttest
12 h after symptom onset in patients with BBB of uncertain ischaemic symptoms
origin may help decide whether to perform emergency angiog- " Isolated posterior myocardial infarction
" ST-segment elevation in lead aVR
raphy with a view to primary PCI. Patients with myocardial in-
farction and RBBB also have a poor prognosis,25 although
RBBB usually will not hamper interpretation of ST-segment ele-
vation. Prompt management should be considered when per- ECG electrocardiogram; LBBB left bundle branch block.
sistent ischaemic symptoms occur in the presence of RBBB,
regardless of whether or not the latter is previously known.
Ventricular pacing may also prevent interpretation of ST-segment
changes and may require urgent angiography toInconrm patients with a suspicion of myocardial ischaemia and
diagnosis
ST-segment
and initiate therapy. Reprogramming the pacemakerallowing an elevation or new or presumed new LBBB, reperfusion
therapy
evaluation of ECG changes during intrinsic heart rhythmmay be needs to be initiated as soon as possible. However, the
ECG may
considered in patients known not to be dependent on ventricular be equivocal in the early hours and, even in proven in-
pacing, without delaying invasive investigation. farction, may never show the classical features of ST-segment ele-
vation
Patients without diagnostic ECG: some patients with acute cor-and new Q waves. If the ECG is equivocal or does not show
evidence
onary occlusion may have an initial ECG without ST-segment to support the clinical suspicion of myocardial infarction,
ECGs
elevation, sometimes because they are seen very early aftershould be repeated and, when possible, the current ECG
should
symptom onset (in which case, one should look for hyper-acutebe compared with previous tracings. Additional recordings
T waves, which may precede ST-segment elevation). of, for example,
It is im- lead V7, V8 and V9 may be helpful in making the
portant to repeat the ECG or monitor the ST segment. In in
diagnosis add-selected cases.
ition, there is a concern that some patients with genuine acute for serum markers is routinely carried out in the
Blood sampling
acute phase
occlusion of a coronary artery and ongoing myocardial infarc- but one should not wait for the results before initiating
reperfusion
tion (such as those with an occluded circumex coronary treatment. Troponin (T or I) is the biomarker of
choice,
artery,26,27 acute occlusion of a vein graft, or left main given its high sensitivity and specicity for myocardial
necrosis.
disease), may present without ST-segment elevation and be In patients who have both a clinically low or intermediate
likelihood
denied reperfusion therapy, resulting in larger infarction and of ongoing myocardial ischaemia and a long prior
duration
worse outcomes. Extending the standard 12-lead ECG with of symptoms, a negative troponin test may help to
avoid
V7V9 leads, while useful, does not always identify these unnecessary emergency angiography in some patients.
If in doubt
patients. In any case, ongoing suspicion of myocardial ischae- regarding the possibility of acute evolving myocardial
infarction,
miadespite medical therapyis an indication for emergency emergency imaging (as opposed to waiting for the bio-
markers
coronary angiography with a view to revascularization, even in to become elevated) allows the provision of timely reper-
patients without diagnostic ST-segment elevation. 3fusion therapy to these patients. If locally available, emergency
coronary angiography
Isolated posterior myocardial infarction: Acute myocardial infarc- is the modality of choice, as it can be fol-
lowed immediately
tion of the infero-basal portion of the heart, often correspond- by primary PCI if the diagnosis is conrmed.
In hospitals
ing to the left circumex territory in which isolated ST-depression or settings in which coronary angiography is not
immediately
e0.05 mV in leads V1 through V3 represents the dominant availableprovided it does not delay transfer
rapid
nding, should be treated as a STEMI. The use of additional conrmation of segmental wall-motion abnormalities by two-
dimensional
posterior chest wall leads [V7V9 e0.05 mV (e0.1 mV in echocardiography may assist in making a decision for
emergency
men ,40 years old)] is recommended to detect ST elevation transfer to a PCI centre, since regional wall-motion
consistent with infero-basal myocardial infarction.abnormalities occur within minutes following coronary occlusion,
well before
Left main coronary obstructionlead aVR ST elevation and infero- necrosis. However, wall-motion abnormalities are
not specic
lateral ST depression: The presence of ST-depression .0.1 mV to acute myocardial infarction and may be due to
other causes
in eight or more surface leads, coupled with ST elevation in such as ischaemia, an old infarction or ventricular
aVR and/or V1 but an otherwise unremarkable conduction
ECG, suggests defects. Two-dimensional echocardiography is of par-
ticular
ischaemia due to multivessel or left main coronary artery ob-value for the diagnosis of other causes of chest pain, such
as pericardial
struction, particularly if the patient presents with haemodynamic effusion, massive pulmonary embolism or dissection
compromise.28 of the ascending aorta (Table 4). The absence of wall-motion ab-
normalities excludes major myocardial infarction. In the emergency
setting, the role of computed tomography (CT) scan should be
 2576 ESC Guidelines

conned to differential diagnosis of acute aortic dissection

monitoring
or of blood oxygen saturation greatly helps when deciding
pulmonary embolism. on the need to administer oxygen or ventilatory support.
Stress-induced (Takotsubo) cardiomyopathy is a recently
Anxietyrecog-
is a natural response to the pain and the circumstances
nized syndrome, which may be difcult to differentiatesurrounding
from STEMI a heart attack. Reassurance of patients and those
as symptoms and ndings, ranging from slight chestclosely
pain toassociated
cardio- with them is of great importance. If the patient
genic shock, may mimic an acute myocardial infarctionbecomesbut the
excessively disturbed, it may be appropriate to adminis-
ECG changes at presentation are usually modest and ter do
a tranquillizer,
not but opioids are frequently all that is required.
correlate with the severity of ventricular dysfunction. It is often
triggered by physical or emotional stress and characterized in its
3.3Cardiac arrest
typical form by transient apical or mid-left ventricular dilation
and dysfunction. Because there is no specic test toMany deaths
rule out myo-occur early during the rst few hours after STEMI, due
toventricularbrillation(VF).Sincethisarrhythmiaoccursmostfre-
cardial infarction in this setting, emergency angiography should not
quentlyatanearlystage,thesedeathsusuallyhappenoutofhospital.
be delayed and, in the absence of myocardial infarction, will show
Therefore
neither signicant culprit coronary artery stenosis nor it is crucial that all medical and paramedical personnel
intracoron-
caring for
ary thrombi. The diagnosis is conrmed by the nding, on imaging, suspected myocardial infarction have access to debrilla-
tionequipmentandaretrainedincardiaclifesupportandthat,atthe
of transient apical- to mid-ventricular ballooning with compensa-
tory basal hyperkinesis, and by disproportionately point of FMC, ECG monitoring be immediately implemented in all
low plasma
patients with suspected myocardial infarction (Table 7).
levels of cardiac biomarkers with respect to the severity of ven-
In patients
tricular dysfunction and, eventually, by recovery of left ventricular with resuscitated cardiac arrest, whose ECG shows
function.29 ST-segment elevation, immediate angiography with a view to
primary PCI is the strategy of choice, provided that the guidelines-
mandated times can be met.3133 Given the high prevalence of
coronary occlusions and potential difculties in interpreting the

3.2Relief of pain, breathlessness

and anxiety
Relief of pain is of paramount importance, not only for humane
Table 7 Cardiac arrest
reasons but because the pain is associated with sympathetic activa-
tion that causes vasoconstriction and increases the workload of
Recommendations
the heart. Titrated i.v. opioids (e.g. morphine) are the analgesics Class a Level b Ref C
All medical and paramedical
most commonly used in this context (Table 6). Intramuscular injec-
personnel caring for a patient
tions should be avoided. Repeated doses may be necessary. Side- with suspected myocardial
effects include nausea and vomiting, hypotension with bradycardia,
infarction must have access
and respiratory depression. Anti-emetics may be administeredto debrillation equipment I C -
concurrently with opioids to minimize nausea. The hypotensionand be trained in cardiac life
and bradycardia will usually respond to atropine and the respira-support.
tory depression to naloxone (0.10.2 mg i.v. every 15 min when
It is recommended to
indicated), which should always be available.
initiate
Oxygen (by mask or nasal prongs) should be administered to ECG monitoring Iat theC -
those who are breathless, hypoxic, or who have heart failure. point of FMC in all
Whether oxygen should be systematically administered to patients patients
withoutheartfailureordyspnoeaisatbestuncertain.30Non-invasive with suspected
Therapeutic
myocardial hypothermia
is indicated early after
infarction.
resuscitation of Icardiac
B arrest
3436
patients who are comatose or
in deep sedation.
Immediate angiography with
Table 6 Recommendations for relief of pain, a view to primary PCI is
breathlessness and anxiety recommended inI patients
B 3133
with
resuscitated cardiac arrest
whose ECG shows STEMI.
Recommendations Class a Level b

Titratedi.v.opioidsareindicatedtorelieve Immediate angiography with

pain. I C a view to primary PCI should
be considered in survivors
of cardiac arrest without IIa B 31, 33
Oxygen is indicated in patients with hypoxia diagnostic ECG ST-segment
I C
(SaO2 <95%), breathlessness, or acute heart elevation but with a high
failure. suspicion of ongoing infarction.
Tranquillizer may be considered in very
anxious patients. IIa C
ECG electrocardiogram; FMC rst medical contact; PCI
percutaneous
coronary intervention; STEMI ST-segment elevation myocardial
i.v. intravenous; SaO2 saturated oxygen. infarction.
aClass of recommendation.
aClass of recommendation.
bLevel of evidence.
bLevel of evidence.
cReferences.
ESC Guidelines 2577

ECG in patients after cardiac arrest, immediate angiography

recorded in every shouldhospital providing care to STEMI patients and
be considered in survivors of cardiac arrest having be amonitored
high index regularly,
of to ensure that simple quality-of-care indica-
suspicion of ongoing infarction (such as the presence
tors are
of chest
met and painmaintained over time. Although still debated,
before arrest, history of established CAD, and abnormal
public reporting
or uncer-of delays may be a useful way of stimulating im-
tain ECG results).31,33 Additionally, there is evidence
provement
that survivors
in STEMI care. If targets are not met, then interventions
of out-of-hospital cardiac arrest who are comatose areneededtoimproveperformance.Thereareseveralcomponents
have improved
neurological outcomes when cooling is provided of early
delayafter
in STEMI
resus- and several ways to record and report them. For
citation. Therefore, these patients should rapidlysimplicity,
receive thera-it is advised to describe and report as shown in Figure 1.
peutic hypothermia.3436 The optimal sequence of cooling and
primary PCI in these patients is unclear. Patient delay: that is, the delay between symptom onset and
The implementation of local/regional protocols toFMC.optimally
To minimize patient delay, the public should be made
manage out-of-hospital cardiac arrest is pivotal toaware
providing
of how to recognize common symptoms of acute myo-
prompt cardiopulmonary resuscitation, early debrillation (if
cardial infarction and to call the emergency services, but the ef-
needed), and effective advanced cardiac life support. Availability
fectiveness fromofpublic campaigns has not yet been clearly
automated external debrillators is a key factor in increasing
established. sur-
38 Patients with a history of CAD, and their families,
vival. Prevention and improved treatment of out-of-hospital
should receive education on recognition of symptoms due to
cardiac arrest is key to reductions in mortality related
acutetomyocardial
CAD. infarction and the practical steps to take,
For a more detailed discussion of these issues, refer to the recent
should a suspected acute coronary syndrome (ACS) occur. It
European Resuscitation Council Guidelines for Resuscitation.
may be wise 37 to provide stable CAD patients with a copy of

their routine baseline ECG for comparison purposes by

medical personnel.
Delay between FMC and diagnosis: a good index of the quality of
3.4Pre-hospital logistics of care care is the time taken to record the rst ECG. In hospitals and
3.4.1 Delays emergency medical systems (EMSs) participating in the care of
Prevention of delays is critical in STEMI for two reasons: rst, the the goal should be to reduce this delay to
STEMI patients,
most critical time of an acute myocardial infarction is the
10 min or veryless.
early phase, during which the patient is often in severe pain
Delay between and FMC and reperfusion therapy: This is the system
liable to cardiac arrest. A debrillator must be made available
delay. It is moreto readily modiable by organizational measures
the patient with suspected acute myocardial infarction as soon
than patient delay. as It is an indicator of quality of care and a pre-
possible, for immediate debrillation if needed. In addition, early
dictor of outcomes. 39 If the reperfusion therapy is primary PCI,
provision of therapy, particularly reperfusion therapy, is critical
the goal should tobe a delay (FMC to wire passage into the culprit
its benet.38 Thus, minimizing delays is associated artery)
with improved
of d90 min (and, in high-risk cases with large anterior
outcomes.Inaddition,delaystotreatmentarethemostreadilyavail-
infarcts and early presenters within 2 h, it should be
able, measurable index of quality of care in STEMI; they should be

Symptom onset FMC Diagnosis Reperfusion therapy

10 min

Patient delay

System delay

Time to reperfusion
therapy

Wire passage in culprit Bolus or

artery infusion
All delays are related to FMC (first medical contact) if primary PCI start if
thrombolysis
Figure 1 Components of delay in STEMI and ideal time intervals for intervention.
 2578 ESC Guidelines

d60 min).40,41 If the reperfusion therapy is brinolysis,

3.4.3theNetworks
goal
is to reduce this delay (FMC to needle) to d30 min.Optimal treatment of STEMI should be based on the implementa-
In PCI-capable hospitals, the goal should be to achieve
tion of anetworks between hospitals with various levels of technol-
door-to-balloon delay d60 min between presentation ogy, inconnected
the hos- by an efcient ambulance service. The goal of these
pital and primary PCI (dened as wire passage into networks
the culprit is to provide optimal care while minimizing delays, in
artery). This delay reects the organization and performance
order to improve clinical outcomes. Cardiologists should actively
of the PCI-capable hospital. collaborate with all stakeholders, particularly emergency physi-
From the patients perspective, the delay between cians,
symptomin establishing
onset such networks. The main features of such a
and provision of reperfusion therapy (either starting
network
brinolysis
are: or
passing a wire through the culprit vessel) is possibly the most
important, since it reects total ischaemic time. It Clear
shoulddenition
be of geographical areas of responsibility
reduced as much as possible. Shared protocols, based on risk stratication and transportation
by trained paramedic staff in appropriately equipped ambulances
3.4.2 Emergency medical system or helicopters
An EMS with an easily remembered and well publicized Pre-hospital
unique triage of STEMI patients to the appropriate institu-
telephone number for medical emergencies is important tions, inbypassing non-PCI hospitals whenever primary PCI can be
order to avoid transportation delays. A teleconsultation
implemented within the recommended time limits
between the EMS and a reference cardiology centre Onisarrival
ideal, at the appropriate hospital, the patient should imme-
but is only available in a limited number of countries.diately
Therefore,
be taken to the catheterization laboratory, bypassing the
a well-trained EMS and an updated and shared, written emergency
STEMI department
management protocol are critically important. AlthoughPatients thepresenting
use to a non-PCI-capable hospital and awaiting
of an EMS decreases the delay and is the preferredtransportation
mode of for primary or rescue PCI must be attended in
initial care for patients with suspected STEMI, it is under-utilized
an appropriately monitored and staffed area
in many countries and, not infrequently, patients self-present
If the diagnosis to of STEMI has not been made by the ambulance
the emergency department. The ambulance servicecrew, has aand critical
the ambulance arrives at a non-PCI-capable hospital,
role in the management of acute myocardial infarction the ambulance
and should should await the diagnosis and, if STEMI is con-
be considered not only a mode of transport but alsormed, a place should
for continue to a PCI-capable hospital.
initial diagnosis, triage and treatment. Pre-hospital diagnosis, triage
and initial emergency treatment in the ambulanceTohas been staff experience, primary PCI centres should perform
maximize
shown to be associated with greater use of reperfusion therapies,
the procedure systematically on a twenty-four hours, seven days a
reduced delays and improved clinical outcomes. 39,42 week In addition,
(24/7) basis for all STEMI patients. Other models, although
EMS transportation allows for the diagnosis and treatment
not ideal,of may include weekly or daily rotation of primary PCI
cardiac arrest. The quality of the care given depends on the
centres train-
or multiple primary PCI centres in the same region. Hos-
ing of the staff concerned. All ambulance personnel should be
pitals that cannot offer a 24/7 service for primary PCI should be
trained to recognize the symptoms of an AMI, administer
allowed to perform primary PCI in patients already admitted for
oxygen, relieve pain and provide basic life supportanother
(Table 8). reason, who develop STEMI during their hospital stay.
All emergency ambulances should be equipped with TheseECGhospitals
recor- should, however, be discouraged from initiating a
ders, debrillators, and at least one person on board trained
service in
limited to daytime- or within-hours primary PCI, since
advanced life support. There is evidence that properly trained confusion with the EMS operators and is unlikely
this generates
paramedical personnel can effectively identify AMItoand matchprovide
the door-to-balloon time and quality of intervention of
timely reperfusion, and that physician-manned ambulances
focussed 24/7 true-primary PCI centres. The current catchment
which are available in only a few countriesare not population
necessary for network systems in European countries that offer
for effective pre-hospital management of AMI.43 Paramedics
primary PCI to the majority of their population is 0.31.0
trained to administer thrombolytics do so safely and effectively.
million. 6 In small service areas the experience may be suboptimal,
Since pre-hospital thrombolysis is an attractive therapeutic
due to an insufcient number of STEMI patients. However, the
option in patients presenting early after symptomoptimal
onset, especial-
size of the catchment area is not clear. Geographical
ly when transfer time is prolonged, 40,44,45 ongoing areas
trainingwhereof the expected transfer time to the primary PCI
paramedics to undertake these functions is recommended,
centre makes evenit impossible to achieve the maximal allowable
in the era of primary PCI. In specic regions, air ambulance
delays indicated in the recommendations below (see section
systems further reduce transportation delays and 3.4.6)
improve out- develop systems for rapid thrombolysis, preferably
should
comes.46 Ambulance staff should be able to recordin-ambulance/out-of-hospital,
an ECG for with subsequent immediate transfer
diagnostic purposes and either interpret it or transmit it, so PCI centres.
to primary
that it can be reviewed by experienced staff in a coronary care
Such networks reduce treatment delays and increase the pro-
unit or elsewhere. The recording, interpretation and, sometimes,
portion of patients receiving reperfusion. 4749 In each network,
teletransmission of an ECG before hospital admission can greatly
the quality of care, time delays and patient outcomes should be
accelerate in-hospital management and increase the probability
measured and compared of at regular intervals and appropriate mea-
timely reperfusion therapy. sures taken to bring about improvement. In a large survey in the
USA, several strategies were associated with shorter delays
 ESC Guidelines 2579

before primary PCI, including the ability to activate

after the
the catheteriza-
ECG diagnosis should be to alert the EMS. But they are
tion laboratory by a single call, preferably whilealso
theable
patient
to administer
is en opioids and antithrombotic drugs (including
route to hospital, expecting laboratory staff to brinolytics
arrive in the if that
cath-is the management strategy), and can undertake
eterization laboratory within 20 min of being paged,
debrillation
having if aneeded.
cardi- In most settings, however, consultation
ologist on site, and using real-time data feedbackwithbetween
a general thepractitionerinstead of a direct call to the
upstream care and the catheterization laboratory. EMSincreases
50 The mostpre-hospital
ef- delay. Therefore, in general, the
fective strategies for increasing the proportion public
of patients
should receiving
be educated to call the EMS, rather than
effective reperfusion and reduce delays to primarythe primary
PCI maycare differ
physician, for symptoms suggestive of myocardial
in other healthcare systems. In order to address infarction.
the issue of
access to primary PCI and effective implementation of networks
across Europe,6 the ESC working group on acute cardiac care,
the European Association of Percutaneous Cardiovascular
3.4.5 Admission Inter-procedures
ventions (EAPCI), and EuroPCR, have joined forces in the Stent
The processing of patients once they arrive in hospital must be
for Life initiative, to improve access to timely, effective primary
speedy, particularly with regard to the diagnosis and administration
PCI through focussed implementation programmes, tailored
of brinolytic agents to or the performance of primary PCI, if indi-
each specic national healthcare setting and attempting to learn for primary PCI should, as often as possible,
cated. Candidates
from success.51 Experience acquired through this initiative,
be admitted directly to the catheterization laboratory, bypassing
across various European systems of care, is published regularly
the emergency department and/or intensive coronary care unit,
and provides tips and resources to increase and improve
while patient thecandidates
imple- for brinolysis must be treated directly
mentation of primary PCI (www.stentforlife.com). in 52
the pre-hospital setting, in the emergency department or in
the coronary care unit.53,54

3.4.4 General practitioners 3.4.6 Logistics

In some countries, general practitioners play aInmajor role in the
the optimal situation (Figure 2), the patient calls a central EMS
early care of acute myocardial infarction and are often
number forthehelp
rst as soon as possible after the onset of chest
to be contacted by patients. If general practitioners respond
pain. The EMS dispatches a fully equipped ambulance with person-
quickly they can be very effective, since they usually knowtothe
nel trained perform and interpret a 12-lead ECG. Once the
patient and can perform and interpret the ECG.ECG Their rst task
reveals ST-segment elevation or new (or presumed new)

Table 8 Logistics of pre-hospital care

Recommendations Class a Level b Ref C

Ambulance teams must be trained and equipped to identify STEMI (with use of ECG recorders and telemetry as
necessary) and administer initial therapy, including thrombolysis where applicable. I B 43

The prehospital management of STEMI patients must be based on regional networks designed to deliver reperfusion
therapy expeditiously and effectively,with efforts made to make primary PCI available to as many patients as possible. I B 47

Primary PCI-capable centres must deliver a 24/7 service and be able to start primary PCI as soon as possible but
always within 60 min from the initial call. I B 6, 52, 55

All hospitals and EMSs participating in the care of patients with STEMI must record and monitor delay times and
I work
B 56, 57
to achieve and maintain the following quality targets:
" rst medical contact to rst ECG d10 min;
" rst medical contact to reperfusion therapy;
" for brinolysis d30 min;
" for primary
All EMSs,emergency PCI d90 min
departments,and (d60 min
coronary if units
care the patient presents
must have withinupdated
a written 120 minSTEMI
of symptom onset or
management directly to a PCI-
protocol,
preferably sharedcapable hospital). networks.
within geographic I C

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

Patients transferred to a PCI-capable centre for primary PCI should bypass the emergency department and be
transferred directly to the catheterization laboratory. IIa B 41, 50, 58

ECG electrocardiogram; EMS emergency medical system; PCI percutaneous coronary intervention; 24/7 24 hours a day, seven days a week; STEMI ST-
segment
elevation myocardial infarction.
aClass of recommendation.
bLevel of evidence.
cReferences.
 2580 ESC Guidelines

STEMI
diagnosisa

EMS or non primary-

Primary-PCI capable PCI
center capable center

Preferably
<60 min
PCI possible <120
min?

Immediate
transfer
Primary-PCI to PCI center Yes No

Preferably
d90 min
(d60 min in early presenters) Preferably
Rescue
d30 min
PCI

Immediate
ly
Immediate
No transfer
Successful to PCI center Immediate
fibrinolysis fibrinolysis
Yes ?

Preferably 324
h
aThe time point the diagnosis is confirmed with
Coronary patient
angiography history and ECG ideally within 10 min from the first
medical contact (FMC).
All delays are related to FMC (first medical contact).
Cath = catheterization laboratory; EMS = emergency medical system; FMC = rst medical contact; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation
myocardial infarction.

Figure 2 Prehospital and in-hospital management, and reperfusion strategies within 24 h of FMC (adapted from Wijns et al.). 4
LBBB, the nearest PCI hospital is informed of the expected
There istime
general of agreement that reperfusion therapy should be
patient arrival. During the ambulance transfer, theconsidered
catheterization
if there is clinical and/or electrocardiographic evidence
laboratory is prepared and staff summoned, if necessary,
of ongoing allowing
ischaemia, even if, according to the patient, symptoms
direct transfer of the patient to the catheterizationstarted
laboratory
.12 h before as the exact onset of symptoms is often
table (bypassing the emergency department and coronary
unclear, or care
when the pain and ECG changes have been stuttering. 59
unit). In cases where the diagnostic ECG has been done elsewhere
There is, however, no consensus as to whether PCI is also bene-
(e.g. in a non-PCI hospital, at a physicians ofce, etc.),
cial the EMS is presenting .12 h from symptom onset in the
in patients
called for transfer and the above chain followed. This scenario
absence of clinicalis and/or electrocardiographic evidence of
best accomplished in a regional network with one ongoing
high-volume
ischaemia. In such asymptomatic late-comers, a small (n
PCI centre, several surrounding non-PCI hospitals 347)
and arandomized
single re- study has shown myocardial salvage and improved
gional EMS. Such regional networks should have predened man-
4-yearsurvivalresultingfromprimaryPCI,comparedwithconserva-
agement protocols for STEMI patients. tive treatment alone, in patients without persistent symptoms 12
48 haftersymptomonset.60,61However,instablepatientswithper-
sistent occlusion of the infarct-related artery, the large (n 2166)
Occluded Artery Trial (OAT) revealed no clinical benet from
3.5Reperfusion therapy routine coronary intervention with medical management, 62,63
3.5.1 Restoring coronary ow and myocardial tissue
beyond that from medical management alone, when the occlusion
reperfusion
was identied 328 days afteracute myocardial infarction, including
For patients with the clinical presentation of STEMI within 12 h
in the subgroup of 331 patients randomized between 24 and 72 h
of symptom onset and with persistent ST-segment elevation or
after onset of infarction.64 A meta-analysis of trials, testing
new or presumed new LBBB, early mechanical (PCI) or pharma-
whether late re-canalization of an occluded infarct artery is bene-
cological reperfusion should be performed as early as possible
cial, provided results consistent with those from OAT. 51
(Table 9).
ESC Guidelines 2581

Table 9 Recommendations for reperfusion therapy Table 10 A summary of important delays and
treatment goals in the management of acute
Recommendations Class a Level b Ref C
ST-segment elevation myocardial infarction
Reperfusion therapy is
indicated in all patients with
symptoms of <12 h duration Delay Target
I A
and persistent ST-segment 65, 66 Preferred for FMC to ECG and diagnosis
elevation or (presumed) new d10 min
LBBB. Preferred for FMC to brinolysis (FMC
to needle) d30 min

Reperfusion therapy Preferred for FMC to primary PCI (door

(preferably primary PCI) is to balloon) in primary PCI hospitals
indicated if there is evidence I C 67 d60 min
of ongoing ischaemia, even if d90 min
symptoms may have started (d60 min if early presenter
>12 h beforehand or if pain with large area at risk)
and ECG changes have been Preferred for FMC to primary PCI
d120 min
stuttering. therapy
Reperfusion (d90 min if early presenter
with primary PCI may Acceptable for primary
with largePCIarea
rather than
at risk)
be IIb B 60, 61 brinolysis if this target cannot be
considered in stable met, consider brinolysis.
patients Preferred for successful brinolysis to
presenting 1224 h angiography 324 h
Routine PCI of a totally
after
occluded
symptom artery
onset. >24 h after
symptom onset in stable
patients without signs of III A 6264
FMC rst medical contact; PCI percutaneous coronary
ischaemia (regardless of intervention.
whether brinolysis was given
or not) is not recommended. should be considered, particularly if it can be given pre-hospital
(e.g. in the ambulance)45,72,73 and within the rst 120 min of
ECG electrocardiogram; i.v. intravenous; LBBB left bundle branch
symptom onset (Figure 2).40,74 It should be followed by consider-
block;
PCI percutaneous coronary intervention. ation of rescue PCI or routine angiography.
aClass of recommendation. Both randomized studies and registries have indicated that long
bLevel of evidence. delays to primary PCI are associated with worse clinical outcomes.
cReferences.
Time delay to reperfusion is dened in section 3.4.1, above. The
PCI-related delay is the theoretical difference between the time
of FMC to balloon ination, minus the time from FMC to start of -
3.5.2 Selection of a strategy for reperfusion brinolytic therapy (i.e. door-to-balloon minus door-to-needle).
Primary PCIdened as an emergent percutaneous TheextenttowhichthePCI-relateddelaydiminishestheadvantages
catheter
intervention in the setting of STEMI, without previous of PCI over brinolysis has been the subject of many analyses and
brinolytic
treatmentis the preferred reperfusion strategy debates. in patients Because
with no specically designed study has addressed this
STEMI, provided it can be performed expeditiously issue, caution
(i.e. withinis needed when interpreting the results of these
guideline-mandated times), by an experiencedpost-hoc team, and analyses. From randomized trials, it was calculated that the
regardless
of whether the patient presents to a PCI-capable PCI-related
hospital delay that may mitigate the benet of mechanical inter-
(Figure 1). If FMC is via an EMS or at a non-PCI-capablevention varies
centre,between 60 and 110 min. In another analysis of these
transfer via the EMS to the catheterization laboratory for PCI primary PCI over brinolytic therapy was calcu-
trials, a benet of
should be implemented immediately. An experienced lated, up to a PCI-related delay of 120 min.66 In 192 509 patients
team
includes not only interventional cardiologists, but included in the US National Registry of Myocardial Infarction
also skilled
support staff. This means that only hospitals with (NRMI)24registry,
an established41themeanPCI-relatedtimedelay,wheremor-
interventional cardiology programme (available tality
24/7)rates of the
should usetwo reperfusion strategies were comparable, was
primary PCI as a routine treatment. Lower mortality calculated
ratesat 114 min. This study also indicated that this delay
among patients undergoing primary PCI are observed varied considerably
in centres according to age, symptom duration and
with a high volume of PCI procedures. Primary infarct location: in
PCI is effective from ,1 h for an anterior infarction in a patient
securing and maintaining coronary artery patency ,65 years of age presenting ,2 h after symptom onset, to almost
and avoids
some of the bleeding risks of brinolysis. Randomized 3 h for clinical
a non-anterior infarction in a patient .65 years of age pre-
trials comparing timely primary PCI with in-hospital senting .2 h after symptom onset. Although these results were
brinolytic
derived
therapy in high-volume, experienced centres have repeatedly from a post-hoc analysis of a registry and reported delays
shown that primary PCI is superior to hospital brinolysis. 6871 inaccurate, this study suggests that an individualized,
are sometimes
(In these trials there was no routine follow-up rescue ratherthanauniform,approachforselectingtheoptimalreperfusion
PCI or angi-
ography.) In settings where primary PCI cannotmodalitycouldbemoreappropriatewhenPCIcannotbeperformed
be performed
within 120 min of FMC by an experienced team, brinolysis
 2582 ESC Guidelines

expeditiously. Taking into account the studies and Because

registries of the
men- need for potent antithrombotic and antiplatelet
tioned above, a target for quality assessment isagents,
that primary
bleeding PCIis more frequent when PCI is performed during
(wire passage) should be performed within 90 min ACSafter
(andFMC STEMI in in
all particular) when compared with bleeding oc-
cases. In patients presenting early, with a largecurring
amountduring of myocar-
an elective procedure. Use of drugs with a more
dium at risk, the delayshould be shorter (,60 min).potentIn patientspre-
antithrombotic effect is often accompanied by an increase
senting directly in a PCI-capable hospital, the goal
in theshould
risk of
also
bleeding,
be to mostly related to the arterial puncture
achieve primary PCI within 60 min of FMC. Although site. Theno specic
radial approach has been shown to reduce the inci-
studies have been performed, a maximum delay dence
of onlyof acute
90 minbleeding events, especially in ACS; in the RadIal
after FMC seems a reasonable goal in these patients.
vs. femorAL
Note that
(RIVAL) access for coronary intervention trial,
these target delays for implementation of primary using PCIradial
are quality
rather than femoral access actually reduced mortality
indicators and that they differ from the maximal inPCI-related
the subset delayof STEMI patients.78 Similar ndings were also
of 120 min, which is useful in selecting primaryobserved
PCI over immediate
in the RIFLE STEACS trial.79 In RIVAL there was,
thrombolysis as the preferred mode of reperfusion however,
(Table an 10).
interaction between benet of the radial access
route and operator experience, suggesting that the benet of
3.5.3 Primary percutaneous coronary intervention radial access over femoral depends upon the radial expertise
3.5.3.1 Procedural aspects of primary percutaneous of operators.
coronary
intervention (Table 11) In primary PCI, drug-eluting stents (DES) reduce the risk of
Approximately 50% of STEMI patients have signicant repeated target vessel revascularization, compared with bare-metal
multivessel
stents (BMS).
disease. Only the infarct-related artery should be treated during 80 There have been concerns about increased risks of

the initial intervention. There is no current evidence to supportthrombosis and reinfarction with DES, compared
very late stent
with BMS.
emergency intervention in non-infarct-related lesions. 75,76 However, use of DES has not been associated with
80The

only exceptions, when multivessel PCI during acute an increased

STEMI is riskjus- of death, myocardial infarction or stent throm-
tied, are in patients with cardiogenic shock in thebosis on long-term
presence of follow up.82 An issue with the routine use of
multiple, truly critical (e90% diameter) stenoses DES in this un-
or highly setting is that it is often difcult to determine reliably
the ability
stable lesions (angiographic signs of possible thrombus orof patients to comply with or tolerate the protracted
lesion disruption), and if there is persistent ischaemia afterantiplatelet
use of dual PCI therapy (DAPT). Whether newer genera-
tions of
of the supposed culprit lesion. However, in patients with multi-DES provide improved clinical outcomescompared
with
vessel disease and cardiogenic shock, non-culprit lesions older generation DES or BMSfollowing primary PCI is
currently
without critical stenoses should not routinely be stented.77 See being tested.
also section 3.5.4.9.

Table 11 Primary PCI: indications and procedural aspects

Recommendations Class a Levelb Ref C

Indications for primary PCI

Primary PCI is the recommended reperfusion therapy over brinolysis if performed by an experienced team within
120 min of FMC. I A 69, 99

Primary PCI is indicated for patients with severe acute heart failure or cardiogenic shock, unless the expected PCI
related delay is excessive and the patient presents early after symptom onset. I B 100

Procedural aspects of primary PCI

Stenting is recommended (over balloon angioplasty alone) for primary PCI. I A 101, 102
Primary PCI should be limited to the culprit vessel with the exception of cardiogenic shock and persistent ischaemia
after PCI of the supposed culprit lesion. IIa B 75, 103
105
If performed by an experienced radial operator, radial access should be preferred over femoral access. IIa B 78, 79
If the patient has no contraindications to prolonged DAPT (indication for oral anticoagulation, or estimated high long-
term bleeding risk) and is likely to be compliant, DES should be preferred over BMS. IIa A 80, 82, 106,
107
Routine thrombus aspiration should be considered. IIa B 8385
Routine use of distal protection devices is not recommended. III C 86, 108
Routine use of IABP (in patients without shock) is not recommended. III A 97, 98

BMS bare-metal stent; DAPT dual antiplatelet therapy; DES drug-eluting stent; IABP intra-aortic balloon pump; PCI percutaneous coronary
intervention.
aClass of recommendation.
bLevel of evidence.
cReferences.
ESC Guidelines 2583

One single-centre randomized trial, the Thrombus

of DAPT Aspiration
prior to hospital admission, rather than in hospital, nor its
during Percutaneous coronary intervention in Acute
use before,
myocardial rather than during, angiography in the setting of STEMI,
infarction (TAPAS) trial,83 showed improvementbut in indices
this is common
of myo- practice in Europe and is consistent with the
cardial reperfusion (ST-segment resolution andpharmacokinetic
myocardial blush) data for oral antithrombotic agents, suggesting
from routine use of manual thrombus aspiration thatbefore
the earliest
a balloon administration would be preferable to achieve
or a stent is introduced into the coronary artery.
early
One-year
efcacy.follow-
up from that trial found a reduction in mortalityAspirin
with thrombus
should preferably
as- be given orally (preferably 150
piration as a secondary endpoint.84 A meta-analysis
300 mg) of TAPAS
including andchewing, to ensure complete inhibition of
several smaller trials found similar results.85 Mechanical
TXA2-dependent thrombec- platelet aggregation, but may be given intraven-
tomy or embolic protection devices have not been ouslyfoundin patients
to who are unable to swallow. There is little clinical
provide similar benets. However, the difference data
in clinical
on the impact
optimal i.v. dosage, but pharmacological data suggest
betweenthevariousmodelsisstillunclear. 86IntherecentINtracor-
that a lower dose range than orally may avoid inhibition of prosta-
onary abciximab inFUsion and aSpiration thrombEctomy
cyclin and therefore
in patientsa bolus dose range of 80150 mg should be
undergoing percutaneous coronary intervention preferred
for Anteriorfor i.v.STaspirin.
segmentelevationMyocardial Infarction(INFUSE-AMI)randomized
The preferred ADP-receptor blockers are prasugrel [60 mg per
trial, thrombus aspiration did not affect infarctos
size.
(p.o.)
87 Several
loadinglarge,
dose, 10 mg maintenance dose] or ticagrelor
randomized trials have been initiated to attempt [180 tomg conrmp.o.the loading dose, 90 mg maintenance dose bis in die
results of TAPAS.88,89 (b.i.d)]; these drugs have a more rapid onset of action and
Operators performing primary PCIs in STEMI should
greaterbe potency
aware and have proved superior to clopidogrel in large
of the importance of selecting an appropriate stent
outcome size.trials.
Most109,110 In the TRial to assess Improvement in Thera-
patients with STEMI have some degree of coronary peuticspasm Outcomes and, by optimizing platelet inhibitioNThrombolysis
thus, intracoronary administration of nitrates isInrecommended
Myocardial Infarction 38 (TRITONTIMI 38), prasugrel
before starting the coronary angiographic sequence
reduced usedthefor composite primary endpoint (cardiovascular death,
stent size selection. The presence of thrombusnon-fatal
can also MI, lead orto
stroke) in clopidogrel-na1ve patients undergoing
stent under-sizing (or otherwise suboptimal deployment),
PCI, either primary which or secondary PCI for STEMI, or moderate-
is a frequent cause of re-stenosis or stent thrombosis
to high-risk in real-life
non-ST-segment elevation acute coronary syndromes
practice. (NSTE-ACS) once coronary angiography had been performed. 109
Preliminary clinical studies have explored theInvalue
the whole
of myocar-cohort, there was a signicant increase in the rate
dial pre- and post-conditioning to improve myocardial
of non-CABG-related
salvage. TIMI major bleeding. In the subset of
A small, randomized trial tested the value of remote
patients conditioning
with STEMI undergoing primary or secondary PCI, the
using intermittent arm ischaemia through fourbenetcycleswas of 5consistent,
min ina- without signicant increase in
tions and deation of a blood pressure cuff.90 This
non-CABG-related
was associated bleeding risk.111 Prasugrel is contraindicated
with improvement in surrogate markers of myocardial
in patients salvage,
with prior stroke/transient ischaemic attack (TIA). Its
measured by myocardial perfusion imaging at use 30 days.
is generally
It is not recommended in patients aged e75 years or
unknown whether this is associated with clinical in patients
benets. The with lower body weight (,60 kg) as it was not asso-
role of post-conditioning has been explored byciated
small with trials,net using
clinical benet in these subsets. The European
either repeated balloon inations or cyclosporine label
infusions.
indicates Thethat, if used in these patients, a similar loading
results are conicting.9195 Given the preliminarydose
nature butofa these
reduced maintenance dose of 5 mg should be consid-
ndings and the small size of the trials, conrmation
ered,ofbut a clinical
no outcome data are available with this dose and there
benet of myocardial pre- and post-conditioningare byalternative
ongoing ran- ADP receptor blockers in this setting. 112 In the
domized trials is warranted before these procedures
PLATelet can inhibition
be and patient Outcomes (PLATO) trial, ticagrelor
recommended in routine clinical practice. reduced the composite primary endpoint (cardiovascular death,
The Counterpulsation to Reduce Infarct Size Pre-PCI-Acute
non-fatal MI, or Myocar-
stroke) and also reduced cardiovascular mortality
dial Infarction (CRISP AMI) trial showed no benetin clopidogrel
from a na1
routine intra-aortic balloon pump (IABP) in anterior myocardial in-
farction without shock,97 and did show increased bleeding, which is
consistent with data available regarding the role of IABPs in
patients with acute myocardial infarction without cardiogenic
shock.(98)
ve or pretreated patients with either STEMI
(planned for primary PCI) or moderate-to-high risk NSTE-ACS
(planned for either conservative or invasive management). 109,110
3.5.3.2 Periprocedural pharmacotherapy (Table 12) Although there was no signicant difference in overall PLATO-
Patients undergoing primary PCI should receive a combination
dened majorofbleeding rates between the clopidogrel and ticagre-
DAPT with aspirin and an adenosine diphosphate (ADP) receptor
lor groups, PLATO-dened and TIMI-dened major bleeding that
blocker, as early as possible before angiography, and a parenteral
was unrelated to CABG surgery was increased with ticagrelor. In
anticoagulant. No trials to date have evaluated the the commencement
subset of patients with STEMI, the benet was consistent.113
Ticagrelor may cause transient dyspnoea at the onset of therapy,
which is not associated with morphological or functional lung ab-
normalities, and which rarely leads to discontinuation. 114 In
PLATO, patients experiencing dyspnoea had a mortality benet
 2584 ESC Guidelines

Table 12 Periprocedural antithrombotic medication in primary percutaneous coronary intervention

Recommendations Class a Levelb Ref C

Antiplatelet therapy
Aspirin oral or i.v. (if unable to swallow) is recommended I B 133, 134
An ADP-receptor blocker is recommended in addition to aspirin. Options are: I A 135, 136
" Prasugrel in clopidogrel-naive patients, if no history of prior stroke/TIA, age <75 years. I B 109
" Ticagrelor. I B 110
" Clopidogrel, preferably when prasugrel or ticagrelor are either not available or contraindicated. I C -
GP IIb/IIIa inhibitors should be considered for bailout therapy if there is angiographic evidence of massive thrombus,
slow or no-reow or a thrombotic complication. IIa C -

Routine use of a GP IIb/IIIa inhibitor as an adjunct to primary PCI performed with unfractionated heparin may be
considered in patients without contraindications. IIb B 137141

Upstream use of a GP IIb/IIIa inhibitor (vs. in-lab use) may be considered in high-risk patients undergoing transfer for
primary PCI. IIb B 127, 128,
137, 142
Options for GP IIb/IIIa inhibitors are (with LoE for each agent):
" Abciximab A 137
" Eptibatide (with double bolus) B 138, 139
" Tiroban (with a high bolus dose) B 140, 141
Anticoagulants
An injectable anticoagulant must be used in primary PCI. I C -
Bivalirudin (with use of GP IIb/IIIa blocker restricted to bailout) is recommended over unfractionated heparin and a
GP IIb/IIIa blocker. I B 124

Enoxaparin (with or without routine GP IIb/IIIa blocker) may be preferred over unfractionated heparin. IIb B 122
Unfractionated heparin with or without routine GP IIb/IIIa blocker must be used in patients not receiving bivalirudin
or enoxaparin. I C 1

Fondaparinux is not recommended for primary PCI. III B 118

The use of brinolysis before planned primary PCI is not recommended. III A 127, 143

ADP adenosine diphosphate; GP glycoprotein; i.v. intravenous; lab catheterization laboratory; PCI percutaneous coronary intervention; TIA
transient ischaemic
attack; UFH unfractionated heparin.
aClass of recommendation.
bLevel of evidence.
cReferences.

of ticagrelor consistent with the overall trial population.

pharmacokinetics
Ticagrelor of clopidogrel, a pro-drug, which requires exten-
may also be associated with asymptomatic bradycardia
sive metabolism
in the rstbefore being active and therefore should be given
week of therapy. None of the more potent agentsin(prasugrel
higher dosesor and as early as possible for it to exert its action in
ticagrelor) should be used in patients with a previous
the emergency
haemorrhagic setting of primary PCI. Furthermore, pre-treatment
stroke or in patients with a moderate-to-severe liver
with disease.
high dose clopidogrel was superior to in-laboratory treatment
When neither of these agents is available (or if they
in observational
are contrain-studies.116,117 All ADP receptor blockers should
dicated), clopidogrel 600 mg p.o. should be given beinstead.
used with
115 Clopi-
caution in patients at high risk of bleeding or with
dogrel has not been evaluated against placebo in signicant
any anaemia.
large-outcome study in the setting of primary PCI,Anticoagulant
but a higher options for primary PCI include unfractionated
regimen of 600 mg loading dose/150 mg maintenance heparindose
(UFH),
in the
enoxaparin and bivalirudin. Use of fondaparinux
rst week was superior to the 300/75 mg regimenininthe thecontext
subset of primary PCI was associated with potential
of patients undergoing PCI in the Optimal Antiplatelet
harm inStrategy
the OASISfor 6 trial and is therefore not recommended. 118
Interventions (OASIS) 7 trial,115 and use of high clopidogrel
There have been no placebo-controlled trials evaluating UFH in
loading doses has been demonstrated to achieve primary
more rapid
PCI but there is a large body of experience with this
inhibition of the ADP receptor. This is consistent agent.
with theDosage should follow standard recommendations for PCI
ESC Guidelines 2585

[i.e. initial bolus 70100 U/kg when no glycoprotein

markers (GP) of reperfusion
IIb/IIIa from the use of tiroban started during
inhibitor is planned or 5060 U/kg when the use theof pre-hospital
GP IIb/IIIa inhi- phase, upstream of primary PCI, and continued
bitors is expected]. There are no solid data recommending
for up to 18 h after the use the procedure (compared to only provisional
of activated clotting time to tailor dose or monitor
use (i.e. UFH notand,systematic
if use) in the catheterization laboratory).
activated clotting time is used, it should not There
delay recanalization
was also a reduction in the composite secondary endpoint
of the infarct-related artery. Enoxaparin (0.5 ofmg/kg
death i.v.infollowed
recurrent myocardial infarction in urgent target
by s.c. treatment) was suggested by severalvesselnon-randomized
revascularization and thrombotic bailout. Finally, in the
studies to provide benet over UFH in primarylarge PCI.119121
HORIZONSAMI
It trial,124 there was no clear benet from
was compared with UFH in one randomized open usinglabel a combination
trial, the of GP IIb/IIIa inhibitor +UFH, compared to
Acute myocardial infarction Treated with primarybivalirudin
angioplasty (with aand substantial fraction of patients receiving UFH
inTravenous enOxaparin or unfractionated heparinbefore to randomization)
Lower is- and the Bavarian Reperfusion Alternatives
chaemic and bleeding events at short- and Long-term
Evaluation-3 follow-up
(BRAVE-3) trial did not nd evidence of a reduction
(ATOLL) trial. The primary composite endpoint in ofinfarct
30-day sizedeath,
from treatment with abciximab in primary PCI
complication of myocardial infarction, procedural
patients failuretreated
and with 600 mg of clopidogrel. 130 Therefore, there
major bleeding was not signicantly reduced (17% is no denitive
reduction, answer regarding the current role of routine use
P 0.063), but there were reductions in the of composite
GP IIb/IIIamain inhibitors
sec- in primary PCI in the era of potent
ondary endpoint of death, recurrent myocardial DAPT, infarction
particularly or ACS when prasugrel or ticagrelor is used, and the
or urgent revascularization, and in other secondary
value ofcomposite
starting upstream of the catheterization laboratory is, at
endpoints such as death, or resuscitated cardiacbest,arrest
uncertain. and Using GP IIb/IIIa inhibitors as bailout therapy in
death, or complication of myocardial infarction.the Importantly,
event of angiographic evidence of large thrombus, slow or
there was no indication of increased bleeding no-reow
from use and of other
enoxa- thrombotic complications is reasonable, al-
parin over UFH.122 Based on these considerationsthough and it has
on thenot been tested in a randomized trial. In conclusion,
considerable clinical experience with enoxaparinthe existing
in otherdata PCI suggest that, if bivalirudin is chosen as the anti-
settings,109111 enoxaparin may be preferred overcoagulant,
UFH. there is no benet of routine addition of GP IIb/IIIa
One large open-label trial demonstrated theblockers
superiority and of a strategy
biva- of bivalirudin alone (with provisional
lirudin over the combination of UFH + GP IIb/IIIa
bailout inhibitor,
use of123 GPa IIb/IIIa blockers) leads to lower bleeding rates
benet driven by a marked reduction in bleeding, and reduced
associated mortality.
with If UFH or enoxaparin is chosen as the anti-
an initial increase in stent thrombosis, whichcoagulant,
disappeared theafter
role of routineas opposed to bailoutuse of GP
30 days.124 Importantly, that study reported IIb/IIIa
a reduction blockers in remains debatable.
all-cause and cardiovascular mortality at 30 days,Intracoronary
which was (i.c.)
main-rather than i.v. administration of GP IIb/IIIa
tained up to 3 years.82 A large fraction of patients
inhibitors in the hasHarmon-
been tested in several small studies and is associated
izing Outcomes with RevascularIZatiON and with Stents somein Acute
benets.131 The Intracoronary abciximab iNFUsion and
Myocardial (HORIZONSAMI) trial, received prerandomization
aspiration thrombectomy for anterior ST-segment ElevAtion Myo-
UFH and approximately 10% bailout GP IIb/IIIa cardial
blockers. Infarction
This is(INFUSE-AMI) trial87 randomized 452 patients
noteworthy because the interpretation of theundergoing
trial result percutaneous
is slightly coronary intervention with bivalirudin
confounded by an interaction between prerandomization
to local delivery useof ofabciximab vs. no abciximab. Intracoronary
UFH, use of a 600mg loading dose of clopidogrel abciximaband reducedreduced the 30-day infarct size, evaluated by magnetic
risk of stent thrombosis.125 resonance imaging, but did not improve abnormal wall motion
Several trials, performed before the routinescore,
use ofST-segment
DAPT, resolution, post-PCI coronary ow or myocar-
mostly using abciximab, had documented clinical dial perfusion.
benets ofThe GP large Abciximab Intracoronary vs. intravenously
IIb/IIIa inhibitors as adjuncts to primary PCI performed
Drug Application with 4 (AIDA-4) randomized trial, which enrolled
UFH.126 The Facilitated INtervention with Enhanced
2065 patientsreperfusion (i.e. more than all previous studies combined)
Speed to Stop Events (FINESSE) trial127 foundfound that routine
no clinical up-benet (but also no harm) in this route of admin-
stream use of abciximab before primary PCI istration
did not yield in terms
clinicalof the composite of death, reinfarction and heart
benet but increased bleeding risk, comparedfailure,
with routine and found use in a borderline reduction in the secondary endpoint
the catheterization laboratory, suggesting that,of heart
for patients
failure.132 going
Therefore, the i.c. route may be considered but
on to primary PCI, there does not appear to be theany i.v. appreciable
route should remain the standard of care for administration
benet and only harm in starting GP IIb/IIIa inhibitors
of GP IIb/IIIa in the inhibitors.
pre-
hospital setting. A post-hoc subset analysis ofRoutine
the FINESSE post-procedural
trial, fo- anticoagulant therapy is not indicated
cussing on patients presenting within 4 h of symptom
after primary onset PCI,to except when there is a separate indication for
non-PCI hospitals and requiring transfer, suggested
either full-dose
they might anticoagulation (due, for instance, to atrial brilla-
derive a survival benet from use of abciximab. tion,
128 mechanical
More recently, valves or LV thrombus) or prophylactic doses for
the ONgoing Tiroban in Myocardial infarctionprevention
Evaluation of 2 venous thromboembolism in patients requiring
(ON-TIME 2) trial129 found an improvement inprolonged
surrogate bed rest.
 2586 ESC Guidelines

3.5.3.3 Prevention and treatment of microvascular 3.5.4.3 Hazards of brinolysis

obstruction
and no-reow Fibrinolytic therapy is associated with a small but signicant excess
Inadequate myocardial perfusion after successful of mechanical
strokes,146 with all of the excess hazard appearing on the rst
opening of the infarct-related artery is often referredafter
day to astreatment. These early strokes are largely attributable
to cerebral
no-reow. The diagnosis of no-reow is usually made when post- haemorrhage; later strokes are more frequently throm-
botic or
procedural thrombolysis in myocardial infarction (TIMI) ow is embolic. Advanced age, lower weight, female gender,
prior
,3, or in the case of a TIMI ow of 3 when myocardial blush cerebrovascular disease, and systolic and diastolic hyperten-
sion on admission
grade is 0 or 1, or when ST resolution within 4 h of the procedure are signicant predictors of intracranial haemor-
rhage. 149
is ,70%.144 Other non-invasive techniques are contrast echocar- In the latest trials, intracranial bleeding occurred in 0.9
1.0% of
diography, single-photon emission tomography, positron emission the total population studied.150,151 Major non-cerebral
tomography (PET), and contrast-enhanced magnetic bleeds (bleeding complications requiring blood transfusion or
resonance
imaging (MRI). that are life-threatening) occur in 413% of the patients
There have been many attempts to treat no-reow treated. intra-Administration of streptokinase may be associated
using150152
coronary vasodilators, i.v. infusion of adenosine with hypotension,
or abciximab, but but severe allergic reactions are rare.
there is no denitive proof that these therapies affect clinical out- of streptokinase should be avoided because of
Re-administration
antibodies,
comes. Likewise, although it is widely used in clinical practice,which can impair its activity, and because of the risk
there
of allergic
is no rm evidence that manual thrombus aspiration reduces distal reactions.
embolization.8386,145
3.5.4.4 Comparison of brinolytic agents
In the Global Utilization of Streptokinase and Tissue plasminogen
activator for Occluded coronary arteries (GUSTO) trial,153
tissue plasminogen activator (tPA; alteplase) with concomitant acti-
3.5.4 Fibrinolysis and subsequent interventions vated partial thromboplastin time (aPTT)-adjusted i.v. UFH
3.5.4.1 Benet of brinolysis resulted in 10 fewer deaths per 1000 patients treated, when com-
Fibrinolysis is an important reperfusion strategy,pared
particularly in
with streptokinase, at the cost of three additional strokes,
those settings where primary PCI cannot be offered to STEMI
only one of which led to a residual neurological decit. Several var-
patients within the recommended timelines. Theiants benet of of
tPAbrino-
have been studied. Double-bolus r-PA (reteplase)
lytic therapy in patients with STEMI is well established: 146 com-
does not offer any advantage over accelerated tPA, except
pared with placebo, approximately 30 early deaths areease
for its prevented
of administration.151 Single-bolus weight-adjusted
per 1000 patients treated within 6 h after symptom onset.
TNK-tPA (tenecteplase) is equivalent to accelerated tPA for
Overall, the largest absolute benet is seen among patients
30-day with and is associated with a signicantly lower rate
mortality
the highest risk, even though the proportional benet may be
of non-cerebral bleedings and less need for blood transfusion. 150
similar. The benet is also seen in the elderly: in aBolus
subgroup of therapy is easier to use in the pre-hospital setting.
brinolytic
3300 patients over the age of 75 years presenting within 12 h of
symptom onset and with either ST-segment elevation or bundle-
3.5.4.5 Contraindications to brinolytic therapy
branch block, mortality rates were reduced signicantly by brino-
Absolute and relative contraindications to brinolytic therapy are
lytic therapy.147
listed in Table 13. Successful resuscitation does not contraindicate
brinolytic therapy. However, lytic therapy is not effective and
increases bleeding, and is not indicated in patients who are refrac-
tory to resuscitation. Prolonged, or traumatic but successful, resus-
3.5.4.2 Time to treatment citation increases bleeding risk and is a relative contraindication to
An analysis of studies in which .6000 patients were brinolysis.
randomized154
to pre-hospital or in-hospital thrombolysis, showed Fibrinolytic
a signicant therapy
re- is recommended within 12 h of symptom
duction (17%) in early mortality with pre-hospital onset if primary
treatment. 72 InPCI
a cannot be performed within 90 min of
beingreduction
meta-analysis of 22 trials,65 a much larger mortality able to administer
was brinolysis and within 120 min from
found in patients treated within the rst 2 h than FMC (seetreated
in those section 3.4.6 and Figure 1) and there are no contraindica-
later. These data support pre-hospital initiation oftions (Table 14).
brinolytic treat- The later the patient presents (particularly after
ment if this reperfusion strategy is indicated. More6 h), the more
recent consideration should be given to transfer for
post-hoc
analyses of several randomized trials and data from primary PCI (inhave
registries preference to brinolytic therapy) as the efcacy
and clinical benet of brinolysis decrease over time, which, in
conrmed the clinical usefulness of pre-hospital brinoly-
later presentations,
sis.40,44,47,143 Most of these studies reported outcome data has the effect of increasing the acceptable
similar to those of primary PCI, provided that earlytime delay before transfer for primary PCI.74
angiography
and PCI were performed in those needing intervention Where(especially
appropriate facilities exist, with trained medical or para-
those who appear to have failed lysis). However,medical
whether staff
pre-able to analyse on-site or to transmit the ECG to the
hospital brinolysis is associated with a similar orhospital for supervision, brinolytic therapy should be initiated in
better clinical
outcome than primary PCI in early-presenting patients has not
been studied prospectively in an adequately sized, randomized
fashion. The ongoing STrategic Reperfusion Early After Myocardial
infarction (STREAM) study is addressing this issue.148
ESC Guidelines 2587

Table 13 Contraindications to brinolytic therapy

Absolute
Previous intracranial haemorrhage or stroke of unknown origin at any time
Ischaemic stroke in the preceding 6 months
Central nervous system damage or neoplasms or atrioventricular malformation
Recent major trauma/surgery/head injury (within the preceding 3 weeks)

Gastrointestinal bleeding within the past month

Known bleeding disorder (excluding menses)

Aortic dissection
Non-compressible punctures in the past 24 h (e.g. liver biopsy, lumbar puncture)
Relative
Transient ischaemic attack in the preceding 6 months
Oral anticoagulant therapy
Pregnancy or within 1 week postpartum
Refractory hypertension (systolic blood pressure >180 mmHg and/or diastolic blood
pressure >110 mmHg)
Advanced liver disease
Infective endocarditis
Active peptic ulcer
Prolonged or traumatic resuscitation

the pre-hospital setting. The aim is to start brinolytic

aspirin, therapy
were randomly assigned to receive tiroban or no tiro-
within 30 min of FMC. For patients arriving at ban.
the hospital,
There was a no evidence that administration of tiroban
realistic aim is to initiate brinolysis within 30 min
improved
(door-to-needle
epicardial or myocardial perfusion.
time). A brin-specic agent should be preferred. Parenteral
The doses anticoagulation
of has been used extensively during
brinolytic agents are shown in Table 15. and after brinolysis and should preferably be given until revascu-
larization (if performed). Otherwise it should be given for at least
48 h or for the duration of hospital stay, up to 8 days. UFH was
3.5.4.6 Adjunctive antiplatelet and anticoagulant found to improve coronary patency after alteplase but not after
therapies
streptokinase.
The doses of antiplatelet and antithrombin co-therapies are 174,175 given Careful dosing and close monitoring of i.v.
in Table 16. UFH therapy is mandatory; aPTT values .70 s are associated
with a higher
Convincing evidence of the effectiveness of aspirin in addition to likelihood of bleeding, reinfarction and death. In
spite of an
brinolysis was demonstrated by the Second International Study of increased risk of major bleeding, the net clinical
benet favoured
Infarct Survival (ISIS-2), in which the benets of aspirin and strepto- enoxaparin over UFH in more recent studies:
in the ASsessment
kinase were seen to be additive.133 The rst dose of 150300 mg of the Safety and Efcacy of a New Thrombo-
lytic 3 (ASSENT
should be chewed or given intravenously (though at a lower dose 3) trial (n 6095), a standard dose of enoxa-
parin given
range) and a lower dose (75100 mg) given orally daily thereafter. in association with tenecteplase for a maximum of
7 days
In the CLopidogrel as Adjunctive Reperfusion TherapyThromb- reduced the risk of in-hospital reinfarction or in-hospital
refractory ischaemia
olysis In Myocardial Infarction 28 (CLARITY-TIMI 28) trial, clopido- when compared with UFH. 158 However, in
the ASSENT-3
grel added to aspirin reduced the risk of cardiovascular events PLUSin trial (n 1639),159 pre-hospital administra-
tion
patients d75 years of age who had been treated with of the same dose of enoxaparin resulted in a signicant in-
crease in
brinolysis, and in the Clopidogrel and Metoprolol in Myocardialthe intracranial haemorrhage rate in elderly patients. In
the large Enoxaparin
Infarction Trial (COMMIT), clopidogrel reduced overall mortality and Thrombolysis Reperfusion for ACute
myocardial
in such patients.156,157 Accordingly, there is a good case for theinfarction TreatmentThrombolysis In Myocardial In-
farction 25
routine use of clopidogrel added to aspirin as an adjunct to lytic(ExTRACTTIMI 25) trial (n 20 506), a lower dose
of enoxaparin
therapy. Prasugrel and ticagrelor have not been studied as adjuncts was given to patients .75 years of age and to
to brinolysis and should not be given. those with impaired renal function (estimated creatinine clearance
, 30 mL/min).
The role of GP IIb/IIIa inhibitors used in conjunction with early Enoxaparin was associated with a reduction in the
risk of death
routine post-thrombolysis PCI is unclear. In the GRupo de Ana lisis and reinfarction at 30 days when compared with a
weight-adjusted
de la Cardiopat1a Isque mica Aguda (GRACIA-3) trial,173 436 UFH dose, but at the cost of a signicant increase
patients with STEMI, treated with tenecteplase, enoxaparin and
 2588 ESC Guidelines

Table 14 Fibrinolytic therapy

Recommendations Class a Levelb Ref C

Fibrinolytic therapy is recommended within 12 h of symptom onset in patients without contraindications if primary
PCI cannot be performed by an experienced team within 120 min of FMC. I A 1, 41

In patients presenting early (<2 h after symptom onset) with a large infarct and low bleeding risk, brinolysis should be
considered if time from FMC to balloon ination is >90 min. IIa B 40, 41, 73

If possible, brinolysis should start in the prehospital setting. IIa A 72, 73, 155
A brin-specic agent (tenecteplase, alteplase, reteplase) is recommended (over non-brin specic agents). I B 150, 153
Oral or i.v. aspirin must be administered. I B 133
Clopidogrel is indicated in addition to aspirin. I A 156, 157
Antithrombin co-therapy with brinolysis
Anticoagulation is recommended in STEMI patients treated with lytics until revascularization (if performed) or for the
duration of hospital stay up to 8 days. I A 118, 153,
The anticoagulant can be: 158164

" Enoxaparin i.v followed by s.c. (using the regimen described below) (preferred over UFH). I A 158163
" UFH given as a weight-adjusted i.v. bolus and infusion. I C 153
In patients treated with streptokinase, fondaparinux i.v. bolus followed by s.c. dose 24 h later. IIa B 118, 164
Transfer to a PCI-capable centre following brinolysis

Is indicated in all patients after brinolysis. I A 165167,

168171
Interventions following brinolysis
Rescue PCI is indicated immediately when brinolysis has failed (<50% ST-segment resolution at 60 min). I A 165, 166
Emergency PCI is indicated in the case of recurrent ischaemia or evidence of reocclusion after initial successful
brinolysis. I B 165

Emergency angiography with a view to revascularization is indicated in heart failure/shock patients. I A 167
Angiography with a view to revascularization (of the infarct-related artery) is indicated after successful brinolysis. I A 168171
Optimal timing of angiography for stable patients after successful lysis: 324 h. IIa A 172

aPTT activated partial thromboplastin time; FMC rst medical contact; i.v intravenous; s.c. subcutaneous; UFH unfractionated heparin.
aClass of recommendation.
bLevel of evidence.
cReferences.

in non-cerebral bleeding complications. The net clinical benet

Table 15 Doses of brinolytic agents (absence of death, non-fatal infarction and intracranial haemor-
rhage) favoured enoxaparin.160,161 Finally, fondaparinux was
Initial treatment Specic shown in the large OASIS-6 trial to be superior to placebo or
contraindications UFH in preventing death and reinfarction, 118,164 especially in
Streptokinase patients who received streptokinase.
(SK) 1.5 million
Priorunits
SK orover In a large trial with streptokinase,176 no mortality reduction was
3060 anistreplase
observed at 30 days, but signicantly fewer reinfarctions were seen
Alteplase min i.v.
(tPA) 15 mg i.v. bolus with bivalirudin (a direct antithrombin, given for 48 ), compared
0.75 mg/kg over 30 min with UFH, though at the cost of a modest and non-signicant
(up increase in non-cerebral bleeding complications. Bivalirudin has
to 50 mg) then 0.5 mg/kg not been studied with brin-specic agents. Thus there is no evi-
over 60 min i.v. (up to 35 dence in support of direct thrombin inhibitors as an adjunct to
mg) 10 units + 10 units i.v. bolus
given 30 min apart brinolysis.
Reteplase
Tenecteplase
(r-PA)Single i.v. bolus: Tenecteplase, aspirin, enoxaparin and clopidogrel comprise the
(TNKtPA) antithrombotic combination that has been most extensively
30 mg if <60 kg studied as part of a pharmacoinvasive strategy, viz. Trial of Routine
35 mg if 60 to <70 kg
ANgioplasty and Stenting after Fibrinolysis to Enhance Reperfusion
40 mg if 70 to <80 kg
45 mg if 80 to <90 kg in acute myocardial infarction (TRANSFER), 168 NORwegian study
50 mg if e90 kg on DIstrict treatment of ST-Elevation Myocardial Infarction
(NORDISTEMI),170 GRACIA-2,177 and GRACIA-3.173

i.v. intravenous.
 ESC Guidelines 2589

Table 16 Doses of antiplatelet and antithrombin co-therapies

Doses of antiplatelet co-therapies

With primary PCI
Aspirin Loading dose of 150300 mg orally or of 80150 mg i.v.if oral ingestion is not possible,followed by a maintenance dose of 75100
mg/day.
Clopidogrel Loading dose of 600 mg orally,followed by a maintenance dose of 75 mg/day.

Prasugrel Loading dose of 60 mg orally,followed by a maintenance dose of 10 mg/day.

In patients with body weight <60 kg, a maintenance dose of 5 mg is recommended.
In patients >75 years, prasugrel is generally not recommended, but a dose of 5 mg should be used if treatment is deemed necessary.
Ticagrelor Loading dose of 180 mg orally,followed by a maintenance dose of 90 mg b.i.d.

Abciximab Bolus of 0.25 mg/kg i.v.and 0.125 g/kg/min infusion (maximum 10 g/min) for 12 h.
Eptibatide Double bolus of 180 g/kg i.v.(given at a 10-min interval) followed by an infusion of 2.0 g/kg/min for 18 h.
Tiroban 25 g/kg over 3 min i.v.,followed by a maintenance infusion of 0.15 g/kg/min for 18 h.
With brinolytic therapy
Aspirin Starting dose 150500 mg orally or i.v. dose of 250 mg if oral ingestion is not possible.
Clopidogrel Loading dose of 300 mg orally if aged d75 years, followed by a maintenance dose of 75 mg/day.
Without reperfusion therapy
Aspirin Starting dose 150500 mg orally.
Clopidogrel 75 mg/day orally.
Doses of antithrombin co-therapies
With primary PCI
Unfractionated heparin 70100 U/kg i.v.bolus when no GP IIb/IIIa inhibitor is planned.
5060 U/kg i.v.bolus with GP IIb/IIIa inhibitors.
Enoxaparin 0.5 mg/kg i.v. bolus.
Bivalirudin 0.75 mg/kg i.v. bolus followed by i.v infusion of 1.75 mg/kg/h for up to 4 h after the procedure as clinically warranted. After cessation
of the 1.75 mg/kg/h infusion, a reduced infusion dose of 0.25 mg/kg/h may be continued for 412 h as clinically necessary.
With brinolytic therapy
Unfractionated heparin 60 U/kg i.v.bolus with a maximum of 4000 U followed by an i.v.infusion of 12 U/kg with a maximum of 1000 U/h for 2448 h.Target
aPTT:5070 s or 1.5 to 2.0 times that of control to be monitored at 3,6,12 and 24 h.
Enoxaparin In patients <75 years of age:
30 mg i.v.bolus followed 15 min later by 1 mg/kg s.c.every 12 h until hospital discharge for a maximum of 8 daysThe rst two
doses should not exceed 100 mg.
In patients >75 years of age:
no i.v.bolus;start with rst s.c.dose of 0.75 mg/kg with a maximum of 75 mg for the rst two s.c.doses.
In patients with creatinine clearance of <30 mL/min,regardless of age,the s.c.doses are given once every 24 h.
Fondaparinux 2.5 mg i.v. bolus followed by a s.c. dose of 2.5 mg once daily up to 8 days or hospital discharge.
Without reperfusion therapy
Unfractionated heparin Same dose as with brinolytic therapy.
Enoxaparin Same dose as with brinolytic therapy.
Fondaparinux Same dose as with brinolytic therapy.

aPTT activatedpartial thromboplastintime;b.i.d. twice aday;GP glycoprotein;i.v. intravenous;PCI percutaneouscoronaryintervention;s.c.

subcutaneous; UFH
unfractionated heparin.

3.5.4.7 Angiography after brinolysis strategy of routine early angiography is recommended if there
Following initiation of lytic therapy, patients should
arebenotransferred
contraindications. Several randomized trials168171,178,179
to a PCI centre (see section 3.4.6). In cases of failed
andbrinolysis,
three contemporary
or if meta-analyses172,180 have shown that
there is evidence of re-occlusion or reinfarction with
early
recurrence
routine post-thrombolysis
of angiography with subsequent PCI
ST-segment elevation, the patient should undergo(ifimmediate
required) reduced
angi- the rates of reinfarction and recurrent ischae-
ography and rescue PCI.165 Re-administration of brinolysis
mia compared
has with a watchful waiting strategy, in which angiog-
not been shown to be benecial. Even if it is likely raphy
that brinolysis
and revascularization were indicated only in patients with
will be successful (ST-segment resolution .50% atspontaneous
6090 min; or induced severe ischaemia or LV dysfunction. The
typical reperfusion arrhythmia; disappearance of benets
chest pain),
of early
a routine PCI after thrombolysis were seen in the
 2590 ESC Guidelines

absence of increased risk of adverse events (stroke 3.5.5

or major
Coronarybleed- bypass surgery and multivessel coronary
ing). Thus, early referral for angiography with subsequent
revascularization
PCI (if
indicated) should be the standard of care after thrombolysis:
The numberthe of patients who require CABG surgery in the acute
so-called pharmacoinvasive strategy. A crucial issuephaseis theof STEMI is small, but CABG may be indicated in patients
optimal delay between lysis and PCI: there was a with
wide anatomy
variation unsuitable for PCI but who have a patent
in delay in trials, from a median of 1.3 h in the Combined
infarct-related
Angio- artery, since patency of this artery provides time
plasty and Pharmacological Intervention versus Thrombolytics
for transfer to the surgical team. It may also be indicated in patients
ALone in Acute Myocardial Infarction (CAPITAL-AMI) in trial
cardiogenic
to shock if the coronary anatomy is not amenable to
16.7 h in the GRACIA-1 trial.171,179 Based on the three
PCI, most
or at the time of repair for patients with mechanical complica-
recent trials, all of which had a median delay between
tions.startCABG ofis rarely used and its benets are uncertain in patients
lysis and angiography of 23 h, a time window of 324 withh failed
after PCI, coronary occlusion not amenable to PCI, and in the
successful lysis is recommended.168170 The ongoing presence
STREAMof148 refractory symptoms after PCI since, in most of these
and GRACIA-4 trials are exploring whether lysis performed
cases, time for implementation of surgical reperfusion will be long
with modern adjunctive therapies, and followed by andsubsequent
the risks associated with surgery are maximal in this setting.
PCI, can achieve similar or better outcomes compared with
primary PCI. 3.5.5.1 Withholding adenosine diphosphate inhibitors for surgery
The risk of bleeding related to surgery must be balanced against
the risk of recurrent ischaemic events related to discontinuation
of therapy,
3.5.4.8 Adjunctive antithrombotic therapy for delayed bearing in mind the nature of the surgery, the ischaemic
percutaneous
coronary intervention after lysis risk and extent of CAD, the time since the acute episode, the time
For patients undergoing PCI several hours or dayssinceafter PCI and the risk of stent thrombosis. Clopidogrel is asso-
brinolysis,
ciated
PCI should be supported by DAPT (aspirin and an ADP antagonist) with an increased risk of bleeding if discontinued less than
5 days
and antithrombin therapy, in doses similar to those used for before surgery. Prasugrel is also associated with a marked
primary PCI. increase in bleeding risk.109 With respect to ticagrelor, data from
the PLATO trial,110 suggest that ticagrelor, discontinued 35
days before CABG surgery, yielded similar CABG-related major
bleeding and transfusions for clopidogrel and ticagrelor. Although
3.5.4.9 Revascularization strategy for ST-segmentnon-fatal
elevationmyocardial infarction and stroke rates in the two
myocardial infarction with multivessel disease groups were not signicantly different in this cohort, there was a
Apart from patients in cardiogenic shock, and in patients
halving with of mortality in the ticagrelor group. In stabilized patients,
continuous ischaemia after opening the supposeditculprit lesion, to stop clopidogrel at least 5 days before surgery
is reasonable
performing PCI of non-culprit vessels in the acute and
setting is gener-
to stop prasugrel 7 days before surgery. Given the PLATO
ally discouraged. The best strategy for STEMI patients with
data, ticagrelormulti- may be discontinued 3 to 5 days before surgery.
vessel disease, who underwent primary PCI of the infarct-related
Whether ADP receptor antagonists should be restarted after
artery in the acute phase with remaining multivesselCABG disease,
surgery is has not been addressed in any specic trial and
still not well established. Among the possible strategies, two that
the optimal timing of such restarting remains uncertain.
are frequently used are either a conservative approachwhich
However, given the reduction of the primary endpoint and mortal-
uses medical therapy after primary PCI, and revascularization
ity with ticagrelor of in the PLATO trial and the continued risk for is-
other arteries only if there are symptoms or evidence of ischaemia
chaemic events in patients post-CABG it is reasonable to restart
in provocative testsor a staged revascularization approach,
DAPT as soon as considered safe in relation to bleeding risk.
using PCI or coronary bypass surgery of non-infarctInarteries
very-high-risk patients in whom cessation of antiplatelet
several days or weeks after primary PCI, often after conrmation
therapy before surgery seems to carry a high risk (e.g. within the
of the stenosis severity with measurements of fractional
rst weeks owafter stent implantation), it has been suggested to
reserve. A multidisciplinary approach is often needed,
switch, including a
before surgery, to a short half-life and reversible antiplate-
heart team and appropriate informed consent of the patient.
let agent, e.g. the GP IIb/IIIa receptor inhibitors tirobanor eptiba-
In STEMI patients with multivessel disease initially treated
tide, with
182 but there is no clinical evidence to support this approach
primary or post-thrombolysis culprit-artery PCI and conrmed
based solely on pharmacokinetic or pharmacodynamic studies. In
presence of ischaemia in non-infarcted territories,thestaged
future,revascu-
the use of cangrelor, an i.v. reversible ADP receptor an-
larization may be performed before discharge or in the days
tagonist, may to permit platelet inhibition to be maintained up to
weeks after initial PCI.181 A comparison of in-hospital complete
surgery in patients discontinuing oral antiplatelet therapy. 183
revascularization [infarct-related artery (IRA) and non-IRA] vs.
conservative approach (IRA only) is being undertaken in the Com-
plete Vs. Lesion-only PRImary PCI Trial (CVLPRIT) and also in the
3.5.6 Non-reperfused
Preventive Angioplasty in Myocardial Infarction (PRAMI) trial. Both patients
3.5.6.1
assess the benet/risk of treating non-infarct-related lesions. Antithrombotic
Like- use
wise, the DANish study of optimal acute treatment Inofpatients
patients presenting
with within 12 h of symptom onset, and in whom
reperfusion
ST-elevation Myocardial Infarction 3 (DANAMI-3) trial is currently therapy was not given, or in patients presenting
testing whether or not to treat non-culprit lesions beyond
in patients 12 h, aspirin, clopidogrel and an antithrombin agent
treated previously with primary PCI. (UFH, enoxaparin or fondaparinux) should be given as soon as
ESC Guidelines 2591

possible (see section 3.4.6).1,156,184 In OASIS-6, fondaparinux was

superior to UFH in a subgroup of 1641 such patients and might Table 17 Special subsets
be the preferred antithrombin for this indication. 185 If PCI is
needed in a patient receiving fondaparinux, i.v. UFH should be Recommendations Class a Levelb Ref C

administered during the procedure, using the same doses as for Both genders must be
primary PCI, to minimize the risk of catheter thrombosis. 186 managed in a similar fashion. I C -
Recommended doses are given in Table 16. None of the oral
agents have been studied in this particular subset of patients, Abut high index of suspicion for
the benet of clopidogrel over placebo was consistent in ACS myocardial infarction must
I B 189
patients, independent of revascularization strategy, in the Clopido-be maintained in women,
diabetics, and elderly patients
grel in Unstable angina to prevent Recurrent Events (CURE)
with atypical symptoms.
trial.187 Ticagrelor was superior to clopidogrel in ACS patients
Special attention must be
who were randomized for an early non-invasive strategy, with given a to proper dosing
similar trend also in those who were not revascularized during antithromboticsI in elderlyB of 190
and
the index hospitalization.188 renal failure patients.

aClass of recommendation.
bLevel of evidence.
3.5.6.2 Invasive evaluation and revascularization cReferences.

Patients sometimes seek medical attention too late and either do

not receive reperfusion therapy, or undergo unsuccessful reperfu-
sion therapy. It has been suggested that achieving late coronary
experience
patency in either of these situations may still have a benecial the same risk of death as men. 195 It is therefore
crucial toLV
effect by preventing adverse LV remodelling, improving provide
func- reperfusion therapy as effectively in women
tion, increasing electrical stability and inducing as in men.vessels
collateral Women generally have lower body weight and are
moreevents
to other coronary beds for protection against future susceptible
(the to bleeding, which is why antithrombotic ther-
apies and
open artery hypothesis). Several trials have evaluated thistheir doses should be used with close attention to
hypoth-
esis, of which the largest by far was the OAT trialbleeding risk. 62 in
(see above),
Elderlyfor
which 20% of the patients received brinolytic therapy patients
the often present with atypical or mild symptoms,
index event. PCI did not reduce the occurrence which
of death, may result in delayed or missed diagnoses of myocardial
reinfarc-
tion or heart failure, compared to medical therapy infarction
alone. (MI). 189 The elderly are at particular risk of bleeding
Further-
more, there was a trend towards excess reinfarctionand other
during complications
four from acute therapies because bleeding
years of follow-up in the invasive therapy group, risk increases
compared with age, because renal function tends to decrease
with
the medical therapy group. A meta-analysis of all and because
trials in thisthe prevalence of comorbidities is high. In addition,
setting provided similar results.63 These studiesobservational
demonstrate studies that have shown frequent overdosing of antith-
rombotic
late PCI of an occluded infarct-related artery after therapies.
myocardial in- 190 It is therefore key to maintain a high
indexover
farction in stable patients has no incremental benet of suspicion for myocardial infarction in elderly patients
who present
optimal medical therapy. Thus, in patients presenting days afterwith atypical complaints and to pay specic atten-
tion to proper
the acute event with a completed myocardial infarction, only dosing of antithrombotic therapies, particularly in
those with recurrent angina or documented residual relation with renal function.
ischaemia,
and proven viability on non-invasive imaging inRenala large dysfunction
myocardialis present in approximately 3040% of patients
territory, may be considered for revascularization with ACSthe
when and is associated with a worse prognosis and
infarct artery is occluded.4 increased bleeding risk.196 Decisions on reperfusion in patients
Special patient subsets with STEMI have to be made before any assessment of renal
Several specic patient subsets deserve particularfunction is available, but it is important to estimate the glomeru-
consideration
(Table 17): lar ltration rate as soon as possible after admission. ACS
Women tend to present later and may have somewhat patients atypical
with chronic kidney disease are frequently overdosed
with antithrombotics,
symptoms more frequently than men.191 Yet myocardial infarc- leading to increased bleeding risk. 190
tion remains the leading cause of death in women The benet
and it of ticagrelor was consistent or enhanced in patients
is there-
with renalfor
fore important to maintain a high degree of awareness dysfunction: GFR , 60 mL/min in the PLATO trial. 197
myocardial infarction in women with potential In patients with
symptoms of is-known or anticipated reduction of renal func-
tion, several
chaemia. In addition, several observational studies have shown antithrombotic agents should be either withheld
that women tend to undergo fewer interventions or their
than doses
men reduced appropriately (Table 18). Ensuring
proper hydration during and after primary PCI, and limiting
and that they also less frequently receive reperfusion
the dose
therapy;192 also that this may not be fully accounted forofbycontrast agents, are important in minimizing the
risk of contrast-induced
the age difference, i.e. women experiencing myocardial infarc- nephropathy.4
tion at a later age than men.193,194 When women Diabeticpatientsareathigherriskofdeath
are given andcomplications,but
effective reperfusion therapy, such as primaryselection
PCI, theyof antithrombotic therapies and reperfusion therapy is
the same as in non-diabetics. The benets of the potent oral
 2592 ESC Guidelines

Table 18 Initial dosing of antithrombotic agents in Table 19 Management of hyperglycaemia in

patients with chronic kidney disease (estimated ST-segment elevation myocardial infarction
creatinine clearance <60 mL/min)
Recommendations Class a Levelb Ref C

Recommendation Measurement of glycaemia is

Aspirin No dose adjustment. indicated at initial evaluation
Clopidogrel No dose adjustment. in all patients, and should
I
be repeated in patientsC -
Prasugrel No dose adjustment.No experience with end-
stage with known diabetes or
renal disease/dialysis. hyperglycaemia.
Ticagrelor No dose adjustment.No experience with end-
stage
Plans for optimal outpatient
renal disease/dialysis. I C -
glucose control and
Enoxaparin No adjustment of bolus dose.Following
secondary prevention must be
thrombolysis,
determined in patients with
in patients with creatinine clearance <30
diabetes before discharge.
mL/min,the The goals of glucose control
No adjustment
s.c. doses are of bolus
given dose.
once every 24 h. in the acute phase should
Unfractionated be to maintain glucose
heparin
Fondaparinux No dose adjustment. concentrations d11.0 mmol/L
No experience in patients with end-stage renal (200 mg/dL) while avoiding
fall of glycaemia <5 mmol/LIIa B 202, 204,
disease or dialysis patients.
(<90 mg/dL).In some patients, 207
Bivalirudin " In patients with moderate renal insufciency (GFR
3059 mL/min) a lower initial infusion rate of 1.4 this may require a dose-
mg/kg/h should be given.The bolus dose should not adjusted insulin infusion with
be changed. monitoring of glucose, as long
" In patients with severe renal insufciency (GFR as hypoglycaemia is avoided.
<30 mL/min) and in dialysis-dependent patients A measurement of
bivalirudin is contraindicated. fasting
Abciximab No specic recommendation.Careful consideration glucose and HbA1c
of bleeding risk. and,in IIa B 208
Eptibatide " In patients with moderate renal insufciency (GFR some cases,a post-
e30 to <50 mL/min),an i.v.bolus of 180 g should discharge
be administered followed by a continuous infusion oral glucose
dose of 1.0 g/kg/min for the duration of therapy. tolerance test
" In patients with severe renal insufciency (GFR should
Routinebe considered
glucose-
<30 mL/min) eptibatide is contraindicated. in
insulin- III A 118, 203
Tiroban In patients with severe renal insufciency (GFR patients with
potassium infusion
<30 mL/min) the infusion dose should be reduced hyperglycaemia
is not
to 50%. but without a history
indicated.
of
diabetes.
HbA1c haemoglobin A1c.
aClass of recommendation.
GFR glomerular ltration rate; i.v. intravenous; s.c. subcutaneous;.
bLevel of evidence.
cReferences.

association with a larger infarct size, whereas elevated HbA 1c

P2Y12 receptor inhibitors (prasugrel or ticagrelor)was
vs. associated
clopidogrelwith long-term effects on outcome through a
higher
are consistent or enhanced in patients with diabetes.198,199baseline risk.201
Although correction of hyperglycaemia by insulin may be of
benet, clinical trials evaluating the effect of metabolic intervention
in patients with STEMI showed conicting results.202 In particular,
3.6Management of hyperglycaemiathe benets of tight glucose control through i.v. insulin shown in
in the acute phase of ST-segment the Diabetes, Insulin Glucose infusion in Acute Myocardial Infarction
(DIGAMI) trial was not conrmed in the subsequent DIGAMI-2
elevation myocardial infarction trial. Glucoseinsulinpotassium infusions were found to be of
Hyperglycaemia on admission is common in patients with an
no value andACS
potentially harmful in a combined analysis of two
and is a powerful predictor of mortality and in-hospital complica- trials.203 Additionally, in critically ill patients,
large randomized
tions. These elevated glucose concentrations have been
there is associated
a high risk of hypoglycaemia-related events when using in-
with an adverse prognosis, both in diabetic and non-diabetic
tensive insulin therapy.204 The denitive answer with regard to
patients. However, elevated glucose concentrations may management
glucose also be in patients with STEMI, including treatment
a sign of disturbed long-term glucose metabolism, thresholds of
because un-
and glucose targets, is lacking and therefore a strategy
diagnosed diabetes or impaired glucose tolerance. of200 It was
strict, recent-
but not too strict glucose control in STEMI seems to
ly shown, in STEMI patients without known diabetes, be athat
practical approach. In the acute phase, it is reasonable to
hyperglycaemia and elevated haemoglobin A1c (HbA 1c) are
manage asso-
hyperglycaemia (i.e. maintain a blood glucose
ciated with a poor prognosis through different mechanisms, with
hyperglycaemia especially predicting short-term prognosis in
ESC Guidelines 2593

concentration d11.0 mmol/L) but absolutely avoid andhypogly-

non-invasive haemodynamic monitoring (arterial and pulmon-
caemia.205,206 This may require a dose-adjustedaryinsulin
arteryinfusion
pressures), respiratory monitoring (continuous positive
with monitoring of glycaemia in some patients.airway pressure and biphasic positive airway pressure), and
Given the frequency of unrecognised diabetessupport,
and impaired
as well as body cooling techniques. The unit should be
glucose metabolism in STEMI patients, it is reasonable
able to manage
to patients with serious renal and pulmonary
measure HbA1c and fasting blood glucose in alldisease.
patientsThe without
desirable organization, structure and criteria of the
known diabetes, who developed hyperglycaemia coronary
during care
the acute
unit have been described in an ESC position
phase (Table 19). If equivocal, an oral glucose tolerance
paper.209 test may
be needed after discharge. This should preferably be measured 4
days after the acute phase. The best therapeutic strategy to specif-
ically lower elevated HbA1c-associated mortality risk Monitoring
4.1.2 remains
uncertain, apart from strategies of secondary prevention
ECG monitoring(antiplate-
for arrhythmias and ST-segment deviations
let therapy, aggressive lipid control, blood pressure control, life-
should be continued for at least 24 h after symptom onset in all
style modication, and cardiac rehabilitation), which
STEMI should be Further monitoring for arrhythmia depends upon
patients.
implemented in all survivors of acute myocardial infarction.
perceived risk and equipment available. When a patient leaves
Whether the results of more intensive, early glycaemic
the coronarytherapy
care unit, monitoring may be continued by telemetry.
with oral agents provides cardiovascular protection is not known
and warrants further study.207
4.1.3 Ambulation
Patients with signicant LV damage should initially rest in bed
before a rst assessment of infarct extent and severity is possible
4.Management during for detection of early heart failure and arrhythmias. In uncompli-
cated cases, the patient can usually sit out of bed on the rst
hospitalization and at discharge day, be allowed to use a commode and undertake self-care and
self-feeding. Ambulation can often start early (particularly in
patients treated via the radial access). Patients who have experi-
4.1Coronary care unit logistics enced complications should be kept in bed for longer and their
and monitoring physical activity resumed as a function of symptoms and extent
4.1.1 Coronary care unit of myocardial damage.
STEMI patients should be admitted to an intensive cardiac care or
coronary care unit (Table 20), or equivalent monitored unit, fol-
4.1.4 Length of stay
lowing reperfusion treatment. A coronary care unit
The optimal
is an intensive
length of stay in the coronary care unit and hospital
care unit designed to provide specialized care to patients
should with car- on an individual basis, considering the
be determined
diovascular disease requiring constant monitoring.
patients
The particular
staff should medical and social situation, including premor-
be thoroughly familiar with the management ofbid ACS, arrhythmias,
health. Over the years, there has been a progressive reduction
heart failure, mechanical circulatory support, and complex invasive

Table 20 Logistical issues for hospital stay

Recommendations Class a Level b Ref C

All hospitals participating in the care of STEMI patients should have a coronary care unit equipped to provide all
I C -
aspects of care for STEMI patients,including treatment of ischaemia,severe heart failure,arrhythmias and common
comorbidities.

Length of stay in the coronary care unit

Patients undergoing uncomplicated successful reperfusion therapy should be kept in the coronary care unit for a
minimum of 24 h,after which they may be moved to a step-down monitored bed for another 2448 h. I C -

Transfer back to a referring non-PCI hospital

Early transfer (same day) may be considered in selected,low-risk patients after successful primary PCI without
observed arrhythmia. IIb C -

Hospital discharge

Early discharge (after approximately 72 h) is reasonable in selected low-risk patients,if early rehabilitation and
adequate follow-up are arranged. IIb B 212, 215,
216

PCI percutaneous coronary intervention; STEMI ST-segment elevation myocardial infarction.

aClass of recommendation.
bLevel of evidence.
cReferences.
 2594 ESC Guidelines

in length of stay after myocardial infarctionespecially

risk offollowing
events decreases with time, early risk assessment is indi-
successful primary revascularizationwithout any cated.
increase Assessment
in sub- of infarct size and resting LV function, usually
sequent mortality, suggesting that earlier dischargeby echocardiography,
is not asso- should be undertaken before discharge.
ciated with late mortality.210,211 Moreover, the Primary
The timing Angioplasty
of further investigations will depend on local facilities
in Myocardial Infarction II (PAMI-II) trial showed that
andlow-risk
whether angiography and PCI have been performed successful-
patients with successful primary PCI could safelyly. beWith
discharged
the increasing use of primary PCI, risk assessment for is-
from hospital at day 3 without non-invasive testing.chaemia
212 Overall,
before discharge has become less important, since it can
early discharge of low-risk patients (within 72 h) beis both
assumedfeasiblethat the infarct-related coronary lesion has been
and safe in patients with uncomplicated STEMI and treated
successful
and stabilized and the presence or absence of signicant
primary PCI.211213 To identify these low-risk patients,
lesions schemes
in other arteries has been assessed. Several risk scores
such as the PAMI-II criteria or the Zwolle primary have
PCI Index
beencan developed, based on readily identiable parameters in
be helpful.212,213 The PAMI II criteria designate asthe
lowacute
risk patients
phasebefore reperfusion.217219 Clinical indicators of
aged ,70 years, with a left ventricular ejection fraction
high risk .45%,
in the acute phase include older age, fast heart rate, hypo-
one- or two-vessel disease, successful PTCA and tension,
no persistent Killip class .I, anterior infarction, previous infarction, ele-
arrhythmias. Nevertheless, a short hospital stay implies
vated initiallimitedserum creatinine and history of heart failure. Malignant
time for proper patient education and up-titrationarrhythmias,
of secondary persistent chest pain and early angina on minimal
prevention treatments. Consequently, these patients exertion shouldare bealso associated with worse outcome.
offered early post-discharge consultations with a cardiologist
If, in spite oforthe angiography performed in the acute phase,
primary care physician and the option of a formalthere rehabilitation
are concerns about inducible ischaemia, an outpatient
program, either in-hospital or on an outpatient basis.
exercise-testing or stress-imaging test (using scintigraphy, echocar-
Current practice may also include early transfer diography
to a local hos- or magnetic resonance imaging) within 46 weeks is
pital following successful primary PCI. In selectedappropriate
low-risk (Table 9). Because of high availability and low cost,
patientsidentied as being asymptomatic without an anyexercise
arrhyth-ECG is commonly used. However, in patients with pre-
mia, haemodynamically stable, not requiring vasoactive
vious myocardial
or mechan- infarction, its accuracy is limited. Stress imaging
ical support and not scheduled for further revascularizationearly
tests are more accurate and allow localization of the ischaemia.
transfer (same day) under adequate monitoring and The supervision
most-validated tests are perfusion scintigraphy and stress
appears safe and feasible.214 echocardiography. In post-myocardial infarction patients, the
detection of residual ischaemia is challenging, due to existing
4.2Risk assessment and imaging wall-motion abnormalities. Computed tomography angiography is
a sensitive technique to detect coronary lesions but, as an anatom-
4.2.1 Indications and timing (Table 21) ical test, it does not assess ischaemia, which remains essential for
After reperfusion treatment, it is important to identify patients
therapeutic at
decisions. If the main concern is arrhythmia, additional
high risk of further events such as reinfarction orelectrophysiological
death, and hope- testing may be needed before discharge, and
fully to intervene in order to prevent these events. Because the

Table 21 Summary of indications for imaging and stress testing

Recommendations Class a Levelb Ref C

At presentation

In the acute phase,when diagnosis is uncertain,emergency echocardiography may be useful.However,if inconclusive or

unavailable and persistent doubt, emergency angiography should be considered. I C -

After the acute phase

All patients should have an echocardiography for assessment of infarct size and resting LV function, I B 220, 221

If echocardiography is not feasible, MRI may be used as an alternative. IIb C -

Before or after discharge
I A 4, 220, 222
For patients with multivessel disease, or in whom revascularization of other vessels is considered, stress testing or
imaging (e.g. using stress myocardial perfusion scintigraphy, stress echocardiography, positron emission tomography or
MRI) for ischaemia
Computed tomography and viability
angiography is indicated.
has no role in the routine management of STEMI patients. III C -

Echocardiography transthoracic echocardiography, or transoesophageal if required; LV left ventricular; MRI magnetic resonance imaging; STEMI ST-
segment elevation
myocardial infarction.
aClass of recommendation.
bLevel of evidence.
cReferences.
ESC Guidelines 2595

repeated assessment of LV ejection fraction afterundertaking.

discharge mayIn this regard, a close collaboration between the car-
be important for selecting candidates for implantation
diologistofand
a the primary care physician is critically important.
cardioverter-debrillator as primary prevention (see
Withbelow).
ever-shorter length of hospital stay in patients with STEMI,
All patients should have their metabolic risk markers
there ismeasured
no longer a clear distinction between acute and chronic
during the index admission, including total cholesterol,
therapies low-density
in STEMI. This chapter summarizes both lifestyle
lipoprotein (LDL) cholesterol, high-density lipoprotein
interventions
cholesterol,
and drug therapies that need to be considered and
fasting triglycerides and plasma glucose, as wellimplemented
as renal function.
before hospital discharge (Table 22).
Since LDL levels tend to decrease during the rst days after myo-
cardial infarction, they are best measured as soon as possible after
admission. 4.4.1 Lifestyle interventions and risk factor control
Key lifestyle interventions include cessation of smoking and tight
4.3Assessment of myocardial viability
blood pressure control, advice regarding diet and weight control,
LV dysfunction after acute myocardial infarctionand may the beencouragement
due to ne- of physical activity. Detailed recommenda-
crosis, to stunning of viable myocardium remainingtionsin arethe available
infarct from the ESC guidelines on prevention. 224 Even
territory, to hibernation of viable myocardium, orthough long-term management of this large group of patients will
to a combination
be the
of all three. Simple stunning should recover within responsibility
2 weeks of the of the primary care physician, these interven-
tions will have
acute ischaemic insult if ischaemia does not persist but, if it does, a higher chance of being implemented if initiated
during
then recurrent stunning may become hibernation and require the hospital stay. In addition, the benets and importance
revascularization for recovery of function. These concepts are of should be explained and proposed to the
of lifestyle changes
patientwho
most relevance in the patient with severely impaired is the key playerbefore discharge. However,
LV function
habits of
after infarction when the need for revascularization to improve a lifetime are not easily changed, and the implementation
and follow-up
function is considered (e.g. after successful brinolysis). of these changes are a long-term undertaking. In this
regard, a close
Multiple imaging techniques, including PET, single-photon emis-collaboration between the cardiologist and the
sion CT, and dobutamine stress echocardiography general
havepractitioner,
been eval- specialist rehabilitation nurses, pharmacists,
uated extensively for assessment of viability and dieticians,
prediction physiotherapists
of is critically important.
clinical outcome after myocardial revascularization. In general,
nuclear imaging techniques have a high sensitivity, whereas techni-
ques evaluating contractile reserve have a somewhat
4.4.1.1 lowerSmoking sensi-
cessation
tivity but higher specicity. MRI has a high diagnostic accuracy
Unselected ACS patients who are smokers are twice as likely to
for assessing transmural extent of myocardial scarpresenttissue,withbut its
a STEMI, compared with non-smokers, indicating a
ability to detect viability and predict recovery ofstrong
wall motion is
prothrombotic effect of smoking. Observational studies
not superior to other imaging techniques.223 The differences
show in
that patients who stop smoking reduce their mortality in
performance of the various imaging techniquesthe aresucceeding
small, and ex- years compared with continued smokers. Stopping
perience and availability commonly determine whichsmoking technique is
is potentially the most effective of all secondary preven-
used. Current evidence is mostly based on observational studies
tion measures,225 and much effort should be devoted to this
or meta-analyses, with the exception of two randomized
end. Patients clinical
do not smoke during the acute phase of a STEMI
trials, both relating to PET imaging.222 Patients with a substantial
and the convalescent period is ideal for health professionals to
amount of dysfunctional but viable myocardiumhelp are smokers
likely to to quit. However, resumption of smoking is
benet from myocardial revascularization and may common improve-
show after discharge, and continued support and advice are
ments in regional and global contractile function, symptoms,
needed duringexer-
rehabilitation. Nicotine replacement, buproprione
cise capacity and long-term prognosis. 220 and antidepressants may be useful. Nicotine patches have been
demonstrated to be safe in ACS patients.226 A randomized study
has also demonstrated the effectiveness of a nurse-directed pro-
gramme.227 A smoking cessation protocol should be adopted by
4.4Long-term therapies for ST-segment each hospital.
elevation myocardial infarction
Coronary heart disease is a chronic condition and patients who
have recovered from a STEMI are at high risk for new events
4.4.1.2 Diet and weight control
and premature death. In fact, in long-term cohorts, Currentmost patients on prevention recommend: 224 (i) eating a wide
guidelines
with STEMI who die do so after discharge from the index
variety of foods; (ii) adjustment of calorie intake to avoid obesity;
event.14 Several evidence-based interventions can improve prog-
(iii) increased consumption of fruit and vegetables, along with
nosis. Even though long-term management of this large
wholegrain group of and bread, sh (especially oily varieties), lean
cereals
patients will be the responsibility of the generalmeatpractitioner,
and low-fat dairy products; (iv) replacing saturated and
these interventions will have a higher chance oftrans being implemented
fats with monounsaturated and polyunsaturated fats from
if initiated during the hospital stay. In addition, vegetable
lifestyle changes
and marine sources, and to reduce total fats (of which
should be explained and proposed to the patient before
less than discharge.
one-third should be saturated) to ,30% of total
However, habits of a lifetime are not easily changedcalorie and the imple-
intake, and (v) to reduce salt intake if blood pressure is
mentation and follow-up of these changes are araised. long-termMany processed and prepared foods are high in salt and
in fat of doubtful quality. There is no evidence for the use of
 2596 ESC Guidelines

antioxidant supplements, low glycaemic index diets or homocyst-

dose-response effect between attendance rate in the group
eine-lowering therapies following STEMI. sessions and outcome rate.231
Obesity is an increasing problem in patients with STEMI.
Current ESC Guidelines dene a body mass index (BMI)
,25 kg/m2 as optimal, and recommend weight reduction when
the BMI is 30 kg/m2 or more, and when waist circumference is
.102 cm in men or .88 cm in women, because weight 4.4.1.6
lossExercise-based
can rehabilitation programme
improve many obesity-related risk factors. However, Exercise-based
it has not rehabilitation has been shown to be effective at
reducing
been established that weight reduction per se reduces all-cause mortality and the risk of reinfarction, as well
mortality.
as improving risk factors, exercise-based capacity and
health-related quality of life after myocardial infarction. 232,233
Yet these benets were established in the era preceding
4.4.1.3 Physical activity
modern treatment of STEMI and a recent British randomized
Exercise therapy has long been used for rehabilitation purposes
trialfailed to demonstrate benets of a rehabilitation programme
following STEMI and the benet of regular physical exercise in
on clinical outcomes or quality of life.234 In another larger rando-
stable CAD patients is also well established. It can reduce the
mized study, a long-term multifactorial, educational and behav-
anxiety associated with the life-threatening illness and improve
ioural intervention was proven to be feasible and sustainable
patient self-condence. Four mechanisms are considered to be im-
over a long period after myocardial infarction, and reduced
portant mediators of a reduced cardiac event rate: (i) improvement
some clinical outcomesparticularly re-infarctionand global
of endothelial function; (ii) reduced progression of coronary
cardiovascular risk.235 An additional benet of rehabilitation pro-
lesions; (iii) reduced thrombogenic risk and (iv) improved collater-
grammes is to help ensure proper titration and monitoring of
alization. In a large meta-analysis, exercise training as part of coron-
key, evidence-based therapies after STEMI. Nowadays, in patients
ary rehabilitation programmes was associated with a 26%
with an uncomplicated course, rehabilitation can often be per-
reduction in cardiac mortality rate in patients with CAD.228 It
formed on an outpatient basis with an efcacy similar to that
should be appreciated that, apart from its inuence on mortality,
of centre-based cardiac rehabilitation.236
exercise rehabilitation can have other benecial effects. Exercise
capacity, cardiorespiratory tness, and perception of well-being
have also been reported to improve, at least during the actual
training period, even in elderly patients. Thirty minutes of moder-
ate intensity aerobic exercise at least ve times per weekResumption
4.4.1.7 is recom- of activities
mended.224 Each step of increase in peak exercise Nocapacity is
generalizable recommendations can be made regarding the
associated with a reduction in all-cause mortalitydelay
risk intothe
resumption of daily activities. Decisions should be indivi-
range of 814%.229 dualized, based on left ventricular function, completeness of revas-
cularization and rhythm control. Extended sick leave is usually
negative and light-to-moderate physical activity after discharge
4.4.1.4 Blood pressure control should be encouraged. Sexual activity can be resumed early if
In hypertensive patients with STEMI, blood pressure adjusted
shouldtobe physical
well ability. Long distance air travel should be
controlled. Data from a retrospective analysis of the PRavastatinweeks if residual ischaemia or left ventricular
avoided for 46
dysfunction is present.
Or atorVastatin Evaluation and Infection TherapyThrombolysis
In Myocardial Infarction 22 (PROVE ITTIMI 22) trial suggest
that, after acute coronary syndromes, the blood pressure goal
should be a systolic ,140 mmHg but not ,110 mm4.4.2 Hg.230 The
Antithrombotic therapy
pharmacotherapy (beta-blockers, ACE inhibitors or ARBs) recom-
4.4.2.2 Aspirin
mended after STEMI, in addition to lifestyle modications
Given its (reduced
established benets in secondary prevention, 237 aspirin
salt intake, increased physical activity and weightshould
loss) usually
be usedhelps
indenitely in all patients with STEMI. The
achieve these goals. Additional drug therapy maydosage
be needed.
of aspirin is debated. In respect of the rst few days of
treatment, the Clopidogrel and aspirin Optimal Dose usage to
reduce recurrent eventsSeventh organization to assess strat-
4.4.1.5 Psychosocial factor interventions egies in ischaemic syndromes (CURRENT/OASIS 7) large, rando-
There is evidence that stress management is usefulmized trialsetting:
in this failed toindemonstrate a difference in hard clinical
outcomes when
a recent trial 362 patients, aged 75 years or younger, with acute comparing low doses (75100 mg/day) or rela-
tively high
myocardial infarction, PCI or CABG within the past 12 months, doses of 300325 mg/day.115 There were, however,
fewer gastro-intestinal
were randomized to receive traditional care or traditional care bleeds with lower doses. For the long
term, low
plus a cognitive behavioural therapy programme focussed on doses (70100 mg) are generally used. Platelet aggrega-
stress management. During a mean of 94 monthstion data suggest that rapid turnover of platelets in diabetic patients
of follow-up,
mayand
the intervention group had a 41% lower rate of fatal require higher doses or more frequent dosing of aspirin to
non-fatal
rst recurrent cardiovascular disease events (45% fewer recurrent inhibition,238,239 but there is no proof of clinical
achieve platelet
acute myocardial infarctions) and a non-signicantbenet of such
28% lower a strategy. Patients with a history of hypersensitivity
all-
to aspirin
cause mortality than the reference group after adjustment for can undergo desensitization and continue therapy indef-
initely.
other outcome-affecting variables. There was also a strong 240242 Patients who are truly intolerant to aspirin can
instead receive clopidogrel (75 mg/day) as long-term secondary
prevention.243
ESC Guidelines 2597

4.4.2.2 Duration of dual antiplatelet therapy and pharmacokinetic

antithrombotic interaction between proton pump inhibitors and
combination therapies after ST-segment elevation the myocardial
new potentinfarction
P2Y12 receptor inhibitors and no clear evidence
DAPT, combining aspirin and an ADP-receptor blockerthat the (clopido-
pharmacokinetic interaction of clopidogrel with some
grel, prasugrel or ticagrelor), is recommended in proton
patients pump with inhibitors has meaningful clinical consequences.257261
STEMI who are undergoing primary PCI (for up to In 12
anymonths),
case, the- benets ofavoidingorminimizingbleedinginpatients
brinolysis (for up to 12 months, although the data at high
available
risk outweigh
pertain the concerns raised by this pharmacokinetic
only to one month of DAPT) and in those patients interaction.
who have not
undergone reperfusion therapy (for at least 1 month The recent
and upAnti-Xa
to 12 Therapy to Lower cardiovascular events in
months). The choice of ADP-receptor blocker has Addition
been discussed
to Standard therapy in subjects with Acute Coronary
previously. While there are no trial data to support
SyndromeThrombolysis
extended In Myocardial Infarction 51 (ATLAS
DAPT, treatment for 12 months after stenting and ACSfor 2TIMI
912 51) trial tested the addition of rivaroxaban, a factor
months following STEMI has traditionally been recommended
Xa antagonist to byaspirin and clopidogrel following ACS. 262 In that
consensus in prior guidelines, regardless of whether
trial, aa low
stent dose of rivaroxaban (2.5 mg twice daily) reduced the
(BMS or DES) was used.1,4,244 Some studies have composite
suggested primary
that endpoint of cardiovascular death, myocardial
there is no benet in extended durations of DAPTinfarction
beyond 6and or stroke, but also all-cause mortality. Interestingly,
12 months after placement of a DES to preventstent ischaemicthrombosis
eventswas reduced by one third. This was associated
and stent thrombosis,245247 but these studies, evenwith when
threefold increases in non-CABG-related major bleeding,
pooled, include a relatively small number of STEMI and patients.
intracranial haemorrhage. Importantly, the high dose of rivar-
Several ongoing large trials, including the Dual oxaban
Antiplatelet(5 mg twice daily) was not associated with similar benets
Therapy (DAPT) study,248 are testing whether longerand was durations
associated with a major increase in the risk of bleeding.
of dual antiplatelet therapy following stenting areTheofATLAS
clinical ACS 2-TIMI 51 trial did not test a combination of riv-
benet. Clearly, after stenting for ACS, particularly
aroxaban
STEMI, with prasugrel or ticagrelor, which might be associated
extended DAPT reduces the risk of stent thrombosis,with even reinfarction
more bleeding. This trial suggests that, in selected
and cardiovascular mortality,249 and more potent patients
DAPT is atasso-
low bleeding risk, the 2.5 mg dose of rivaroxaban may
ciated with greater clinical benets post-ACS of anybe considered in patients who receive aspirin and clopidogrel
type.109,110,188 Pending the results of ongoing trials,
afteraSTEMI.
912 However, a phase III trial of another factor Xa antag-
months duration of DAPT is recommended, withonist a strict
(apixaban), the Apixaban for Prevention of Acute Ischemic
minimum of one month for patients who have receivedand Safety a BMSEvents (APPRAISE-2) trial,263 failed to nd similar ben-
and six months for those who received a DES. Itets is important
of adding atohigh dose of apixaban to single or DAPT in a
inform patients and their physicians about the needvery-high-risk
to avoid ACS population. Finally, darexaban and dabigatran
premature discontinuation of DAPT. were both tested in phase-II dose-ranging trials in post ACS
In patients with STEMI and with atrial brillationpatients,
and the264,265need with, in both cases, dose-dependent increases in
for permanent anticoagulation after primary PCImajor [based bleeding
on but no signal of added efcacy when adding anti-
Cardiac failure, Hypertension, Age, Diabetes, Stroke
coagulant(Doubled)
therapy to antiplatelet therapy in this setting. In conclu-
(CHADS2) or Cardiac failure, Hypertension, Age sion,e75 the role of novel anticoagulants in combination with DAPT in
(Doubled), Diabetes, Stroke (Doubled) VAScularsecondary
disease, Age prevention of STEMI remains under discussion. The
6574 and Sex category (Female) (CHA2DS2-VASc) substantial
scores of mortality
e benet seen with a low dose of rivaroxaban
2],250,251 triple therapy, combining aspirin, an ADP
combined
receptor with
an-aspirin and clopidogrel is intriguing but interpret-
tagonist and an oral anticoagulant, is recommended ation of to the
reducetotality of evidence for the class is difcult.
the burden of thromboembolic complications associated with
atrial brillation and minimize the risk of stent thrombosis.
4.4.3 Beta-blockers
4
However, it is also associated with an increase in The benet ofcompli-
bleeding long-term treatment with beta-blockers after STEMI
cationsand should therefore be used for the shortest
is wellpossible
established, dur- although mostly from trials pre-dating the
ation.252,253 This is an area of controversy, with advent
missingofevidence,
modern reperfusion therapy and pharmacotherapy.
and several consensus documents have tried toThe offerrolealgorithms
of routine early i.v. administration, on the other hand,
for decision-making.253255 Moreover, in STEMI patients
is less rmlywith established.
an Oral administration of beta-blockers
indication for anticoagulation, and in whom stents are needed,
appears se-
to be associated with benet, but high, early i.v. dosage
lection of BMS over DES would appear to minimize was the durationwith
associated of an early hazard and increased mortality in
triple therapy and therefore the risk of bleeding. theThese
largebenets
COMMIT trial.266 Thus, early i.v. use of beta-blockers is
should be weighed against the benets of DES incontraindicated
preventing in patients with clinical signs of hypotension or
restenosis.4,253 congestive heart failure. Early use may be associated with a
Gastric protection, preferably with a proton pumpmodest inhibitor,
benet in low-risk, haemodynamically stable patients. In
should be considered for patients with a historymost of gastrointestinal
patients, however, it is prudent to wait for the patient to sta-
bleeding and is appropriate for patients with multiple risk factors
bilize before starting a beta-blocker and to use oral, rather than i.v.,
for bleeding, such as advanced age, concurrentadministration.
use of anticoagu- In contemporary trials utilizing primary PCI, beta-
lants, steroids or non-steroidal anti-inammatoryblockers
drugs including
have not been investigated, although it is not unreason-
high dose aspirin, and Helicobacter pylori infection.
able256 to There is no their benet to this setting.
extrapolate
 2598 ESC Guidelines

4.4.4 Lipid-lowering therapy of dihydropyridines, on the other hand, have failed to show
The benets of statins in secondary prevention have benetbeenafterun- STEMI and they should therefore only be prescribed
equivocally demonstrated,267 and specic trials havefor clear
demonstrated
indications such as hypertension or angina. 278
the benet of early and intensive statin therapy. 268,269 The recent
meta-analysis of trials comparing more- vs. less-intensive
LDL-cholesterol lowering with statins indicated that, compared
with less-intensive regimes, more-intensive statin therapy pro-
duced reductions in the risks of cardiovascular 4.4.7
death, Angiotensin-converting
non-fatal enzyme inhibitors
and angiotensin
myocardial infarction, ischaemic stroke and coronary revasculariza- receptor blockers
It is well established
tion. For every 1.0 mmol/L reduction in LDL cholesterol, these that angiotensin-converting enzyme (ACE)
inhibitors
further reductions in risk were similar to the proportional reduc- should be given to patients with an impaired ejection
fraction (,40%)
tions in the trials of statin vs. control. Therefore, statins should or who have experienced heart failure in the
early phase.
be given to all patients with acute myocardial infarction, irrespect- A systematic overview of trials of ACE inhibition
early in STEMI
ive of cholesterol concentration. This treatment should be started indicated that this therapy is safe, well tolerated
and associated
early during admission, as this increases patient adherence after with a small but signicant reduction in 30-day mor-
tality, with
discharge, and given at high doses, as this is associated with earlymost of the benet observed in the rst week. 279 Opi-
nions
and sustained clinical benets.270 The treatment goal is an still differ as to whether to give ACE inhibitors to all patients
or to
LDL-cholesterol concentration of ,1.8 mmol/L (,70 mg/dL). high-risk patients only. Patients who do not tolerate an ACE
inhibitor
The use of lower-intensity statin therapy should be considered inshould be given an angiotensin receptor blocker
(ARB).280
patients at increased risk of side-effects from statins (e.g.Usetheof ACE inhibitors should be considered in all
patients
elderly, patients with hepatic or renal impairment, with previouswith atherosclerosis, but, given their relatively modest
effect, their long-term
side-effects of statins or the potential for interaction with essential use cannot be considered mandatory in
post-STEMI
concomitant therapy).270 Lipids should be re-evaluated 46 weeks patients who are normotensive, without heart
failure,
after the ACS, to determine whether the target levels have beenor have neither LV systolic dysfunction nor diabetes. Two
trials have
reached and regarding safety issues; the statin dose can then be evaluated ARBs, in the context of STEMI, as alternatives
to ACE inhibitors:
adjusted accordingly. Given trial results with high doses of atorvas- the Optimal Trial In Myocardial infarction with
the Angiotensin
tatin and simvastatin and the risks associated with high-dose sim- II Antagonist Losartan (OPTIMAAL) trial with
vastatin,271 the strongest trial data available solosartan
far favour (50 mg) failed to show either superiority or non-
atorvastatin at a dose of 80 mg daily, unless a high dose when
inferiority compared with captopril (50 mg three times
of statin
daily).
was poorly tolerated previously in that patient. In patients280 Conversely, the VALsartan In Acute myocardial iNfarc-
tion Trial with
known to be intolerant of any dose of statin, treatment compared
eze- valsartan alone (160 mg twice daily), full-dose
timibe should be considered. captopril (50 mg three times daily), or both (80 mg twice daily and
50 mg
The consumption of n-3 polyunsaturated fatty acids reduced three times daily).281 Mortality was similar in the three
groups but
mortality in survivors of myocardial infarction in one study, 272 discontinuations were more frequent in the groups re-
ceiving captopril.
but failed to affect clinical outcomes in two more recent trials Therefore valsartan, in the dosages used in the
trial, represents
using modern evidence-based prevention therapies and therefore an alternative to ACE inhibitors in patients who
cannot be recommended in routine practice.273,274 have clinical signs of heart failure and/or an ejection fraction
d40%, particularly in patients who do not tolerate ACE inhibitors.

4.4.5 Nitrates
The routine use of nitrates in STEMI has not been 4.4.8 Aldosterone
shown to be of antagonists
value and is not therefore recommended. Intravenous nitrates Post-AMI
The Eplerenone may Heart failure Efcacy and SUrvival Study
(EPHESUS) trial
be useful during the acute phase in patients with hypertension or randomized 6642 post-STEMI patients with LV
dysfunction (ejection
heart failure, provided there is no hypotension, right ventricular in- fraction ,40%) and heart failure or diabetes
to eplerenone,
farction or use of phosphodiesterase type 5 inhibitors in the pre- a selective aldosterone blocker, or placebo. 282
After a mean
vious 48 h. In the acute and stable phase, nitrates remain valuablefollow-up of 16 months, there was a 15% relative re-
agents to control anginal symptoms. duction in total mortality and a 13% reduction in the composite of
death and hospitalization for cardiovascular events. Serious hyper-
kalaemia was more frequent in the group receiving eplerenone.
4.4.6 Calcium antagonists The results suggest that aldosterone blockade may be considered
A meta-analysis of trials involving calcium antagonists early inpatients
for post-STEMI the with an ejection fraction d40% and heart
course of a STEMI showed a trend towards harm. 275 There is no
failure or diabetes, provided that the creatinine concentration is
case for using calcium antagonists for prophylactic
,221 purposes
mmol/L (2.5 in mg/dL) in men and ,177 mmol/L (2.0 mg/dL)
the acute phase. In the chronic phase, verapamil may be helpful
in women, and potassium is ,5.0 mEq/L. Routine monitoring of
to prevent reinfarction and death.276,277 Thus, in patients
serum with con-
potassium is warranted.
traindications to beta-blockers, particularly in the presence of ob-
structive airway disease, calcium antagonists are a reasonable
option for patients without heart failure, although caution has to
4.4.9Routine
be exercised in patients with impaired LV function. Magnesium,
use glucoseinsulinpotassium, lidocaine
There is no benet in the routine administration of magnesium,
glucoseinsulinpotassium, or lidocaine in patients with STEMI.
 ESC Guidelines 2599

Table 22 Routine therapies in the acute, subacute and long term phase of ST-segment elevation myocardial infarction

Recommendations Class a Level b Ref C

Active smokers with STEMI must receive counselling and be referred to a smoking cessation programme. I B 225

Each hospital participating in the care of STEMI patients must have a smoking cessation protocol. I C -
Exercise-based rehabilitation is recommended. I B 232, 233

Antiplatelet therapy with low dose aspirin (75100 mg) is indicated indenitely after STEMI. I A 237

In patients who are intolerant to aspirin, clopidogrel is indicated as an alternative to aspirin. I B 243
DAPT with a combination of aspirin and prasugrel or aspirin and ticagrelor is recommended (over aspirin and
clopidogrel) in patients treated with PCI. I A 109, 110

DAPT with aspirin and an oralADP receptor antagonist must be continued for up to 12 months after STEMI,with a
strict minimum of: I C
" 1 month for patients receiving BMS I C
245247,
283
" 6 months for patients receiving DES IIb B

In patients with left ventricular thrombus, anticoagulation should be instituted for a minimum of 3 months. IIa B 344346
In patients with a clear indication for oral anticoagulation (e.g.atrial brillation with CHA 2DS2-VASc Score e2 or
mechanical valve prosthesis), oral anticoagulation must be implemented in addition to antiplatelet therapy. I C -

If patients require triple antithrombotic therapy,combining DAPT and OAC,e.g.because of stent placement and an
obligatory indication for OAC, the duration of dual antiplatelet therapy should be minimized to reduce bleeding risk. I C -

In selected patients who receive aspirin and clopidogrel,low-dose rivaroxaban (2.5 mg twice daily) may be considered
if the patient is at low bleeding risk. IIb B 262

DAPT should be used up to 1 year in patients with STEMI who did not receive a stent. IIa C -

Gastric protection with a proton pump inhibitor should be considered for the duration of DAPT therapy in patients at
high risk of bleeding. IIa C 256

Oral treatment with beta-blockers should be considered during hospital stay and continued thereafter in all STEMI
patients without contraindications. IIa B 1, 266

Oral treatment with beta-blockers is indicated in patients with heart failure or LV dysfunction. I A 284288

Intravenous beta-blockers must be avoided in patients with hypotension or heart failure. III B 266
Intravenous beta-blockers should be considered at the time of presentation in patients without contraindications,with
high blood pressure, tachycardia and no signs of heart failure. IIa B 266

A fasting lipid prole must be obtained in all STEMI patients,as soon as possible after presentation. I C -
It is recommended to initiate or continue high dose statins early after admission in all STEMI patients without
contraindication or history of intolerance, regardless of initial cholesterol values. I A 267

Reassessment of LDL-cholesterol should be considered after 46 weeks to ensure that a target value of d1.8 mmol/L
(70 mg/dL) has been reached. IIa C 270

Verapamil may be considered for secondary prevention in patients with absolute contraindications to beta-blockers
and no heart failure. IIb B 276

ACE inhibitors are indicated starting within the rst 24 h of STEMI in patients with evidence of heart failure,LV
systolic dysfunction, diabetes or an anterior infarct. I A 279

AnARB,preferably valsartan,is an alternative toACE inhibitors in patients with heart failure or LV systolic dysfunction,
particularly those who are intolerant to ACE inhibitors. I B 280, 281

ACE inhibitors should be considered in all patients in the absence of contraindications. IIa A 289, 290
Aldosterone antagonists,e.g.eplerenone,are indicated in patients with an ejection fraction d40% and heart failure or
diabetes, provided no renal failure or hyperkalaemia. I B 282

ACE angiotensin-converting enzyme; ACS acute coronary syndrome; ARB angiotensin receptor blocker; BMS bare metal stent; DAPT dual
antiplatelet therapy;
DES drug-eluting stent; LDL low-density lipoprotein; LV left ventricular; STEMI ST-segment elevation myocardial infarction.
aClass of recommendation.
bLevel of evidence.
cReferences.
 2600 ESC Guidelines

evaluated early by transthoracic echocardiography/Doppler. Echo-

5.Complications following cardiography is the key diagnostic tool and should be performed to
assess LV function and volumes, valvular function, extent of myo-
ST-segment elevation myocardial
cardial damage, and to detect mechanical complications. Doppler
infarction evaluation permits assessment of ow, gradients, diastolic function
and lling pressures. Chest X-ray will assess the extent of pulmon-
ary congestion and detect other important conditions such as
5.1Haemodynamic disturbances pulmonary infection, chronic lung disease and pleural effusion.
5.1.1 Heart failure Unexpected deterioration of the patients clinical status, with
Myocardial dysfunction frequently occurs during the evidence
acute andof haemodynamic
sub- compromise, should trigger a re-
acute phases following STEMI. Rapid improvement evaluation with a repeat echocardiographic examination, specical-
in ventricular
function is usually seen following successful earlylyrevascularization
searching for evidence of progressive LV dysfunction or mechan-
of the infarct-related artery by PCI or thrombolysis.ical complications.
However, if
In selected
the STEMI results in transmural injury and/or microvascular ob-patients who do not respond adequately to conven-
tionalwith
struction, especially of the anterior wall, pump failure measuresand
patho- who have evidence of ongoing ischaemia,
logical remodellingand the clinical symptoms andpersistent
signs of heartST elevation or new LBBBthe need for further revas-
failuremay complicate the acute phase and resultcularization
in chronic should be considered.
Patients
heart failure. Heart failure may also be the consequence of with
sus- extensive myocardial injury during the acute phase
tained arrhythmias or mechanical complications of may develop the symptoms and signs of chronic heart failure. This
STEMI.
diagnosis
The diagnosis of clinical heart failure during the acute and requires
sub- management according to guidelines for the
acute phases of STEMI is based on typical symptoms treatment
such as ofdys-
chronic heart failure.284 Selected patients with symp-
pnoea, signs such as sinus tachycardia, a third hearttomatic,
sound chronic
or heart failure and a reduced ejection fraction or
pulmonary rales, and some objective evidence of electrical dyssynchrony, as evidenced by QRS prolongation, may
cardiac dysfunc-
satisfy criteria
tion, such as LV dilatation and reduced ejection fraction. Natriuret-for implantation of a cardioverter-debrillator,
cardiac resynchronization therapy (CRT), or a cardiac resynchroni-
ic peptides [B-type natriuretic peptide (BNP) and N-terminal
pro-BNP] rise in response to increased myocardialzation therapy debrillator. These criteria are presented in a
wall stress
and have been shown to be useful biomarkers in the recent guideline focusing on device therapy. 291
management
of patients with chronic heart failure. Evidence has established their
role in diagnosing, staging, making admission/discharge decisions
and identifying patients at risk for adverse clinical5.1.1.1
events. Normal
Hypotension
levels have strong negative predictive value. Their value
Hypotensionin acute
is dened as persistent systolic blood pressure
heart failure following MI is less well established, ,90
duemmHg.
to the It may be due to heart failure but also to correctable
abrupt changes in LV systolic and diastolic function that follow treatable rhythm disturbance or mechanical compli-
hypovolaemia,
MI and the relatively long half-lives of these peptides.
cations.Importantly,
If prolonged, hypotension may cause renal dysfunction,
conditions such as LV hypertrophy, tachycardia, ischaemia,
acute tubular renalnecrosis and reduced urinary output.
dysfunction, advanced age, obesity and treatment may inuence
levels. There are no denitive cut-off values in patients with signs
5.1.1.2 Pulmonary congestion
and symptoms of heart failure following acute MI, and levels
Pulmonary congestion is characterized by dyspnoea with basal
should be interpreted in conjunction with the patients clinical
pulmonary rales, reduced arterial oxygen saturation, pulmonary
condition.281
congestion on chest X-ray and clinical response to diuretic and/
LV dysfunction is the single strongest predictor of mortality fol-
or vasodilator therapy.
lowing STEMI. The mechanisms responsible for LV dysfunction in
the acute phase include myocardial loss and remodelling due to in-
5.1.1.3
farction, ischaemic dysfunction (stunning), atrial and Low output states
ventricular
arrhythmias and valvular dysfunction (pre-existing or new). states combine signs of poor peripheral perfusion and
Low output
hypotension,
There is frequently evidence of both systolic and diastolic renal dysfunction and reduced urinary output.
dysfunc-
Echocardiography
tion. Co-morbidities such as infection, pulmonary disease, renal may reveal poor left ventricular function, a
mechanical
dysfunction, diabetes or anaemia often contribute to the clinical complication or right ventricular infarction.
picture. The degree of heart failure following myocardial infarction
5.1.1.4Class
may be categorized according to the Killip classication: Cardiogenic
I, no shock
Cardiogenic
rales or third heart sound; Class II, pulmonary congestion withshock complicates 610% of all cases of STEMI and
rales over ,50% of the lung elds, sinus tachycardia remains
or thirda leading cause of death, with hospital mortality rates
heart sound; Class III, pulmonary oedema with rales approaching
over 50% 50%. of 292 Although shock often develops early after
the lung elds and Class IV, cardiogenic shock. the onset of acute myocardial infarction, it is typically not diag-
Haemodynamic assessment should be based on nosed thorough on hospital
phys- presentation.292 In the SHould we emergently
ical examination, continuous ECG telemetry of heart revascularize
and rhythm, Occluded coronaries for Cardiogenic shocK
oxygen saturation, blood pressure monitoring and(SHOCK) trial registry,293 of the patients who eventually devel-
hourly urinary
output. Patients suspected of having heart failureopedshould shock
be during hospitalization, this occurred within 6 h in
about 50% and within 24 h in 75%. There is a wide spectrum of
ESC Guidelines 2601

clinical symptoms, signs and haemodynamic ndings of thethatpatients

dene the haemodynamic status. It is essential to detect and
presence and severity of cardiogenic shock and are manage
directly atrial
related
and ventricular dysrhythmias, valvular dysfunction,
to short-term outcome.294296 Patients typically present
post-infarction
with ischaemia and hypertension. Co-morbidities, such
hypotension, evidence of low cardiac output (restingas infection,
tachycardia, pulmonary disease, renal dysfunction, diabetes,
altered mental status, oliguria, cool peripheries) anaemia
and pulmonary or other laboratory abnormalities often contribute to
congestion. The haemodynamic criteria for cardiogenic
the clinical
shock picture.
are Patients with heart failure usually require
a cardiac index of ,2.2 L/min/m2 and an increasedoxygenwedgetherapy
pressure and monitoring of oxygen saturation by oximeter
of .18 mmHg. Additionally, diuresis is usually ,20with
mL/h. a target
Shock .95% is (90% in chronic obstructive pulmonary disease
also considered present if i.v. inotropes and/or anpatients)
IABP is needed
and periodic blood gas assessment. Care should be taken,
to maintain a systolic blood pressure .90 mmHg. in It patients
is usuallywith asso-serious obstructive airways disease, to avoid hyper-
ciated with extensive LV damage, but may occurcapnia.in rightIn ventricular
hypotensive patients, volume loading should be
infarction. Both short- and long-term mortality appear
attemptedto bein asso-
patients without evidence of volume overload or
ciated with initial LV systolic dysfunction and thecongestion.
severity of mitralMost patients require diuretic therapy, and an im-
regurgitation.295 The presence of right ventricularprovement
dysfunction in ondyspnoea supports the diagnosis.
early echocardiography is also an important predictor In mildof anheart failure (Killip Class II), i.v. loop diuretics and/
adverse prognosis, especially in the case of combined
or i.v. left-
nitrates
andare usually effective in achieving preload reduction
right ventricular dysfunction. 296 Baseline and follow-up
and alleviating
stroke congestion and dyspnoea. Hypertension, if
volume index and follow-up stroke work index appear present, to beshould
the be treated promptly to prevent further decompen-
most powerful haemodynamic predictors of 30-day sation.
mortality
ACE inhibitors/ARBs
in and aldosterone antagonists improve
patients in cardiogenic shock and are more useful dyspnoea,
than traditional
attenuate the remodelling process, improve survival
haemodynamic variables.297 Therefore, cardiogenic andshock
may be charac-
initiated early in the absence of hypotension, hypovol-
terization and management do not necessarily need aemia invasive
or renal meas-
dysfunction.
urement of LV lling pressure and cardiac output through
In moderate
a heart failure with pulmonary oedema
pulmonary catheter but LV ejection fraction and associated
(Killip Classmech- III), i.v. morphine reduces dyspnoea and relieves
anical complications should be evaluated urgently anxiety.
by two- Intravenous loop diuretics and/or i.v. vasodilators are indi-
dimensional Doppler echocardiography. 295298 cated for dyspnoea in patients without hypotension (blood pres-
Management of cardiogenic shock complicatingsure acute.90myocar-
mmHg). In patients who tolerate the apparatus,
dial infarction includes haemodynamic stability, achieved
non-invasive withventilation with continuous positive airway pressure
medical therapy or mechanical circulatory support, therapy
and emergent
is effective in treating pulmonary oedema. Endotracheal
revascularization by means of PCI or CABG surgery. intubation
Drug treat- and ventilatory support may be required in patients
ment of cardiogenic shock complicating STEMI includes
unable to antithrom-
achieve adequate oxygenation, or with evidence of
botics, uids, vasopressors and inotropes. Antithrombotics
hypercapnia shoulddue to respiratory exhaustion. Systolic arterial blood
be given as routinely indicated in STEMI patients,pressure
although (SBP)
clopido-
should determine the choice of inotropic or vaso-
grel, prasugrel or ticagrelor should be deferred until
pressor
angiography,
agent. In hypotensive patients with signs and symptoms of
because immediate CABG surgery may be necessary. heart Fluid
failure admin-
and poor organ perfusion (SBP , 90 mmHg), dopa-
istration is often used on a pathophysiological basis,
minealthough
(inotropic/vasopressor)
it has should be considered. In patients
not been analysed in randomized trials. In other with
formssignsof shock,
and symptoms of heart failure and adequate blood pres-
however, early uid support improves survival. Similarly,
sure (BPvasopres-
.90 mm Hg) dobutamine (inotropic) or levosimendan
sors and inotropes are used due to their favourable (inotropic/vasodilator)
haemodynamic may be preferable. Noradrenaline (vaso-
effects, but none have produced consistent symptomatic
pressor) may improve-be preferable in patients with hypotension and
ment and many induced a reduction in survival that signs mayof cardiogenic
be asso- shock or septicaemia. The inotropic effect of
ciated with the deleterious cellular effects of these
levosimendan
drugs. 299 A is independent of beta-adrenergic stimulation and
recent randomized trial compared norepinephrine represents
with dopamine an alternative for patients on chronic beta-blocker
in 1679 patients with shock, including 280 with cardiogenic
therapy. In patients
shock. with an SBP ,100 mmHg, initiation of
Dopamine was associated with higher mortality in therapy
the cardiogenic
without a bolus is recommended.284 Ultraltration to
shock subgroup and more adverse eventsmainlyreduce arrhythmic uid overload refractory to diuretics may be useful, espe-
eventsfor the overall cohort.300 Therefore, when blood
cially in pres-
patients with hyponatraemia.
sure is low, norepinephrine should be the rst choice. In severe
It should heart failure with cardiogenic shock (Killip
be used at the lowest possible dose and titrated Class
until theIV) systolic
it is essential to detect alternative causes of hypotension
arterial pressure rises to at least 80 mmHg. Subsequentlyand
such as hypovolaemia, drug-induced hypotension, arrhythmias,
because its beta-2-adrenergic effectdobutamine tamponade,
can be givenmechanical complications or right ventricular infarc-
simultaneously to improve contractility. tion. Intravenous inotropes/vasopressors are usually required to
maintain an SBP .90 mmHg and adequate cardiac output and
renal perfusion.
5.1.2 Management of heart failure following ST-segment
elevation myocardial infarction (Table 23) Invasive haemodynamic assessment with a pulmonary artery
General measures include: taking a thorough history,catheter may permit
including pre- careful adjustment of lling pressures and as-
vious medical therapy, and a physical examination sessment of cardiac output. In selected patients who are not
with assessment
 2602 ESC Guidelines

Table 23 Treatment of heart failure and left ventricular dysfunction

Recommendations Class a Levelb Ref C

Treatment of mild heart failure (Killip class II)

Oxygen is indicated to maintain a saturation >95%. I C -

Loop diuretics,e.g.furosemide:2040 mg i.v.,is recommended and should be repeated at 14 h intervals if necessary. I C -

i.v. nitrates or sodium nitroprusside should be considered in patients with elevated systolic blood pressure. IIa C -
AnACE inhibitor is indicated in all patients with signs or symptoms of heart failure and/or evidence of LV dysfunction
in the absence of hypotension, hypovolaemia, or renal failure. I A 309312

AnARB (valsartan) is an alternative toACE inhibitors particularly ifACE inhibitors are not tolerated. I B 281

An aldosterone antagonist (epleronone) is recommended in all patients with signs or symptoms of heart failure and/or
evidence of LV dysfunction provided no renal failure or hyperkalaemia. I B 282

Hydralazine and isosorbide dinitrate should be considered if the patient is intolerant to bothACE inhibitors andARBs. IIa C 313

Treatment of moderate heart failure (Killip class III)

Oxygen is indicated. I C -
Ventilatory support should be instituted according to blood gasses. I C -

Loop diuretics,e.g.furosemide:2040 mg i.v.,are recommended and should be repeated at 14 h intervals if necessary. I C -

Morphine is recommended.Respiration should be monitored.Nausea is common and an antiemetic may be required.
Frequent low-dose therapy is advisable. I C -

Nitrates are recommended if there is no hypotension. I C -

Inotropic agents:
" Dopamine IIa C -

" Dobutamine (inotropic) IIa C -

" Levosimendan (inotropic/vasodilator). IIb C -

An aldosterone antagonist such as spironolactone or eplerenone must be used if LVEF d40%. I B 282, 314

Ultraltration should be considered. IIa B 315

Early revascularization must be considered if the patient has not been previously revascularized. I C -
Treatment of cardiogenic shock (Killip class IV)

Oxygen/mechanical respiratory support is indicated according to blood gasses. I C -

Urgent echocardiography/Doppler must be performed to detect mechanical complications,assess systolic function and
loading conditions. I C -

High-risk patients must be transferred early to tertiary centres. I C -

Emergency revascularization with either PCI or CABG in suitable patients must be considered. I B 100
Fibrinolysis should be considered if revascularization is unavailable. IIa C -

Intra-aortic balloon pumping may be considered. IIb B 1, 98, 305

LV assist devices may be considered for circulatory support in patients in refractory shock. IIb C -
Haemodynamic assessment with balloon oating catheter may be considered. IIb B 316

Inotropic/vasopressor agents should be considered:

" Dopamine IIa C -

" Dobutamine IIa C -

" Norepinephrine (preferred over dopamine when blood pressure is low). IIb B 300, 317

ACE angiotensin-converting enzyme; ARB angiotensin receptor blocker; CABG coronary artery bypass graft; i.v. intravenous; LV left ventricular;
LVEF left
ventricular ejection fraction; PCI percutaneous coronary intervention.
aClass of recommendation.
bLevel of evidence.
cReferences.
ESC Guidelines 2603

responding adequately to conventional measures thereandwaswho noexhibit

improvement in 30-day mortality. 306 Based on these
evidence of ongoing ischaemia, persistent ST elevation
results, percutaneous
or new LVADs cannot be recommended as rst-line
LBBB, early revascularization with brinolysis, PCI treatment
or CABG in cardiogenic shock but may be considered on an indi-
should be considered. A strategy of early revascularizationpref-
vidual basis, taking into account the experience of the group, as
erably at a tertiary care centrehas demonstrated wellbenets
as patient
in age and co-morbidities. Similarly, in settings other
terms of improved functional status and long-term thansurvival.
STEMI, such The as transplant candidates not responding to stand-
SHOCK trial demonstrated that STEMI patients ard withtherapy,
cardiogenic surgical implantable LVADs307 or extracorporeal life
shock, undergoing emergency revascularizationsupport with PCI involving
or membrane oxygenators 308 have been used as
CABG surgery, have substantially improved long-termdestinationsurvival,
therapy or a bridge to transplant. Again, the evidence
compared with patients having initial intensive for medical
benettherapy
is still limited.
fol-
lowed by no- or late in-hospital revascularization: a nding consist-
ent with observations from registries.100,293 Despite
5.1.3longer time toand conduction disturbances
Arrhythmias
treatment, transferred patients are a selected population
in the acute with
phase
similar adjusted in-hospital mortality, and benet from emergency
Arrhythmias and conduction disturbances are common during the
revascularization in the same way as direct-admit earlypatients. 301 Rec-
hours after myocardial infarction. According to recordings
ognizing patients at highest risk for development from of cardiac
shock may monitors implanted within 11 +5 days of an acute
facilitate the early transfer of high-risk patientsmyocardial
before the infarction,
onset the incidence is 28% for new-onset atrial b-
of haemodynamic instability. Cardiogenic shockrillation,
is the one circum-
13% for non-sustained ventricular tachycardia, 10% for
stance in which it may be acceptable to embark on emergency
high-degree atrioventricular block (d30 beats per minute lasting
revascularization of multivessel disease.100,302 for e8 s), 7% for sinus bradycardia (d30 beats per minute
IABP counterpulsation is the most widely usedlasting
mechanical
for e8 s), 5% for sinus arrest (e5 s), 3% for sustained ven-
support for the treatment of cardiogenic shock,tricular
based on the
tachycardia, and 3% for ventricular brillation. 318 The long-
benecial effect of aortic diastolic ination and rapid
termsystolic
prognosticdea- signicance of early (,48 h) VF or sustained ven-
tion, improving myocardial and peripheral perfusiontricular and reducing (VT) in patients with acute myocardial infarc-
tachycardia
afterload and myocardial oxygen consumption.tion Evidence
is still regarding
controversial. In patients with acute myocardial
its efcacy, in the setting of acute myocardial infarction
infarction, compli-
early VF/VT identied those at increased risk for
cated by cardiogenic shock, has been reviewed30-day recently for
mortality (22% vs. 5%) as compared to those without VF/
patients in the prebrinolytic, the brinolytic and VT.
the319primary
ACE inhibitors/ARBs reduced the 30-day mortality in
PCI eras.98 Owing to the lack of randomized trials,theseonly registries
patients. Other studies have conrmed that beta-blocker
were evaluated, and showed conicting results for the three
therapy, given eras,in the rst 24 h after AMI in patients with early sus-
with mortality risk differences of 29% and 18% tained
in favour of IABP
VF/VT, wasinassociated with decreased early mortality
the prethrombolytic and thrombolytic eras, andwithoutan increase of 6% heart failure.320 Prospective randomized
worsening
in mortality with IABP in the primary PCI era. Concordantly, the
studies are warranted to clarify the clinical implications of
Treat angina with Aggrastat and determine Costearly-onset
of Therapyventricular
with an In-arrhythmias in this setting.
vasive or Conservative Strategy (TACTICS) trial,303 which investigated
Arrhythmias after the early reperfusion period may be a
the efcacy of counterpulsation in thrombolysedmanifestation
STEMI patients of a serious underlying condition, such as continu-
with hypotension, possible cardiogenic shock oring heart failure, ischaemia, pump failure, altered autonomic tone,
myocardial
showed no benet in terms of mortality from adding IABPand
hypoxia, to electrolyte- (e.g. hypokalaemia) and acid-base dis-
thrombolysis for the overall study cohort, but showed a favourable
turbances, all of which require attention and corrective mea-
decrease in 6-month mortality for patients withsures.more High-degree
severe atrioventricular block was a more powerful
haemodynamic impairment allocated to IABP. Similarly,
predictoranother
of cardiac death than tachyarrhythmias in patients
small pilot trial in 40 patients with cardiogenic shock,
with left who were
ventricular ejection fraction ,40% after myocardial
undergoing primary PCI, showed benecial effects infarction.318 the
on BNP for
IABP group, but no benet in terms of the primary trial outcome
[change in serial Acute Physiology And Chronic Health Evaluation
II (APACHE-II) scoring].304 Another recent meta-analysis suggests
5.1.3.1 Supraventricular
a survival benet from IABP in patients with cardiogenic shock. 305 arrhythmias
Atrial brillation
Overall, despite common use in clinical practice, there is somewhat complicates some 628% of myocardial infarctions
and is frequently
conicting evidence with respect to the benet of IABP in cardio- associated with severe LV damage and heart
failure. 318,321 Episodes may last from minutes to hours and are
genicshock, whichis probably largely relatedto the difcultyofper-
forming randomized trials in this setting. often repetitive. In many cases, the arrhythmia is well tolerated
Mechanical LV assist devices (LVADs) have been andused
no specic treatment is required, other than anticoagulation
in patients
(Table 24).
not responding to standard therapy, including inotropes, uids and 250 In some instances, the fast ventricular rate contri-
butes Atorecent
IABP, but evidence regarding their benets is limited. heart failure, requiring prompt treatment. Adequate
meta-analysis examined three randomized trials comparingisaimportant
rate control per- in order to reduce myocardial oxygen
demand,
cutaneous LVAD vs. IABP in a total of 100 patients. Although and can be accomplished by administration of beta-
blockers
the LVAD appeared safe and demonstrated better haemodynamics, or possibly calcium antagonists, either orally or intraven-
ously (see recommendations below). In patients with extensive myo-
cardial damage or severe LV dysfunction, rate control is more
 2604 ESC Guidelines

Table 24 Management of atrial brillation

Recommendations Class a Level b Ref C

Rhythm control should be considered in patients with atrial brillation secondary to a trigger or substrate that has
been corrected (e.g. ischaemia). IIa C -

Acute rate control of atrial brillation

Intravenous beta-blockers or non-dihydropyridine CCB (e.g.diltiazem,verapamil) d are indicated if there are no clinical
signs of acute heart failure. I A 323

Amiodarone or i.v. digitalis is indicated in case of rapid ventricular response in the presence of concomitant acute
heart failure or hypotension. I B 324

Cardioversion I C -
Immediate electrical cardioversion is indicated when adequate rate control cannot be achieved promptly with
pharmacological agents in
Intravenous amiodarone is patients
indicatedwith atrial brillation
for conversion and on-going
to sinus rhythm inischaemia,severe haemodynamic
stable patients with recent onset compromise
atrial or
heart failure.
brillation and structural heart disease. I A 250

Digoxin (LoEA),verapamil,sotalol,metoprolol (LoE B) and other beta-blocking

III A B C agents
250 (LoE C) are ineffective in
converting recent onset atrial brillation to sinus rhythm and should not be used for rhythm control (although beta
blockers or digoxin may be used for rate control).

Recommended doses of anti-arrhythmic agents are given in Guidelines for management of patients with atrial brillation. 250
CCB calcium-channel blocker; i.v. intravenous; LoA level of evidence; LV left ventricular.
aClass of recommendation.
bLevel of evidence.
cReferences.
dCalcium antagonists should be used cautiously or avoided in patients with heart failure because of their negative inotropic effects.

safely achieved with i.v. digoxin with or without concomitant

5.1.3.2 Ventricular
ad- arrhythmias (Table 25)
ministration of i.v. amiodarone, related to the negativeVentricular
inotropicpremature beats are almost universal on the rst day
effect of beta-blockers or calcium antagonists. Urgent of theelectrical
acute phase and complex arrhythmias (multiform com-
cardioversion may be considered in patients presenting plexes,with
short runs or the R-on-T phenomenon) are common.
atrial brillation and intractable ischaemia or haemodynamic
Their valuein-as predictors of VF is questionable. No specic
stability. Several,321,322 but not all,318 studies have therapy
suggested is required.
that
development of atrial brillation in the setting of acute Ventricular
myocardial tachycardia should be differentiated from acceler-
infarction is an independent predictor of all-cause atedmortality,
idioventricular
irre- rhythma consequence of reperfusion that
spective of the treatment given. Atrial brillation not is only
usually harmlessin which the ventricular rate is ,120 beats
increased the risk for ischaemic stroke during the hospitalization
per minute. Runs of non-sustained VT (lasting ,30 s) are not re-
but also during follow-up, even paroxysmal atrial brillation
liable predictive
(AF) markers for early VF and may be well tolerated,
that has reversed to sinus rhythm at the time of discharge.
not necessarily
321 requiring treatment. More prolonged episodes
Patients with atrial brillation and risk factors for thromboembol-
may cause hypotension and heart failure and may degenerate
ism should therefore be adequately treated with oral intoanticoagula-
VF. Since there is no evidence that suppression of asymptom-
tion. Because AF will generally require anticoagulation,atic non-sustained
when VT prolongs life, there is no indication to treat
choosing a stent in these patients, the benets of DES non-sustained
on resten- VT, unless it is associated with haemodynamic in-
osis should be weighed carefully against the substantialstability.
bleeding
Sustained and/or haemodynamically unstable VT requires
risks that are associated with the prolonged combinationsuppressive
of therapy, summarized below and outlined in the guide-
triple antithrombotic therapy. Specic guidance withlines respect
for ventricular
to se- arrhythmias.325 Electrical cardioversion (which
lection of a rhythm- or rate control strategy, as well requires
as on thesedation
type in conscious patients) is indicated if any VT per-
of stent and combination antiplatelet and anticoagulant sists andtherapy,
always indicated if the patient is haemodynamically un-
has been given in the recent guidelines on the management
stable.326 Itofis the safest method for termination of sustained VT
atrial brillation.250 in acute STEMI. If the patient appears haemodynamically stable,
Other supraventricular tachycardias are rare and i.v. are amiodarone,
usually self- sotalol or lidocaine (if the VT is thought to be
limited. They may respond to vagal manoeuvres. Intravenous
related to ongoing
ad- myocardial ischaemia) may be initiated for its
enosine may be considered in this setting, if atrial termination,
utter is ruledbut conversion rates are low. Amiodarone is the
out and the haemodynamic status is stable; the ECG only should
anti-arrhythmic
be agent without severe pro-arrhythmic effects
monitored during administration. If not contraindicated,in patients
beta-with reduced LV function, and is therefore the drug
blockers may be effective. Electrical cardioversionof should
choice bein patients with reduced left ventricular function. In a
employed if the arrhythmia is poorly tolerated. cohort of patients (in whom the majority had CAD) with stable
 ESC Guidelines 2605

Table 25 Management of ventricular arrhythmias and conduction disturbances in the acute phase

Recommendations Class a Levelb Ref C

Direct current cardioversion is indicated for sustainedVT andVF. I C -

Sustained monomorphicVT that is recurrent or refractory to direct current cardioversion:
should be considered to be treated with i.v. amiodarone.d IIa C -

may be treated with i.v. lidocaine or sotalol. e IIb C -

Transvenous catheter pace termination should be considered ifVT is refractory to cardioversion or frequently
recurrent despite antiarrhythmic medication. IIa C -

Repetitive symptomatic salvoes of non-sustained monomorphicVT should be considered for either conservative
management (watchful waiting) or treated with i.v.beta-blocker, e or sotalol,e or amiodarone.d IIa C -

PolymorphicVT
" must be treated by i.v.beta-blocker e I B 320, 336
" or i.v.amiodarone d I C -
" urgent angiography must be performed when myocardial ischaemia cannot be excluded I C -
" may be treated with i.v.lidocaine IIb C 330
" must prompt assessment and correction of electrolyte disturbances consider magnesium. I C -
" should be treated with overdrive pacing using a temporary transvenous right ventricular lead or isoprotenerol
infusion. IIa C -

In cases of sinus bradycardia associated with hypotension, AV block II (Mobitz 2) or AV block III with bradycardia that causes hypotension
or heart failure:
" intravenous atropine is indicated I C -
" temporary pacing is indicated in cases of failure to respond to atropine. I C -
" urgent angiography with a view to revascularization is indicated if the patient has not received prior reperfusion
therapy. I C -

Management of ventricular arrhythmias and risk evaluation for sudden death on long term
Specialized electrophysiological evaluation of ICDI implantation
A for secondary prevention of sudden cardiac death is
333
indicated in patients with signicant LV dysfunction,who suffer from haemodynamically unstable sustainedVT or who
are resuscitated from VF occurring beyond the initial acute phase.
Secondary preventive ICD therapy is indicated to reduce mortality in patients with signicant LV dysfunction,and
haemodynamically unstable sustainedVT or survivedVF,not occurring within the initial acute phase. I A 333

Risk evaluation for sudden cardiac death should be performed to assess indication for primary preventive ICD therapy
by assessing LVEF (from echocardiography) at least 40 days after the acute event in patients with LVEF d40%. I A 333

Recommendeddoses ofanti-arrhythmic agentsaregivenintheGuidelinesfor management of patientswith ventriculararrhythmiasandthe prevention ofsudden

cardiacdeath.325
AV atrioventricular; i.v. intravenous; ICD implantable cardioverter debrillator; LVEF left ventricular ejection fraction; VF ventricular brillation; VT
ventricular
tachycardia.
aClass of recommendation.
bLevel of evidence.
cReferences.
dQT-prolonging agents should not be used if baseline QT is prolonged.
eIntravenous sotalol or other beta-blockers should not be given if ejection fraction is low.

sustained VT (but without acute myocardial infarction),

retrospective
both i.v.analysis of STEMI patients who developed sustained
amiodarone and procainamide were relatively ineffective,
VT/VF (n with
1126, 5.9%) in the GUSTO IIB and III trials, all-cause
25% and 30% conversion rates for amiodarone and deathprocainamide,
was compared among those receiving amiodarone (n 50,
respectively. Clinically important hypotensive reactions
4.4%), led
lidocaine
to ces-(n 664, 59.0%) or no anti-arrhythmic (n
sation of amiodarone and procainamide infusion or 302,immediate
26.8%). Among patients who survived 3 h, amiodarone was
direct current cardioversion in 6% and 19% of patients,
associated with increased mortality at 30 days and 6 months but
respectively.327 lidocaine was not, an observation that reinforces the need for ran-
Ventricular brillation: immediate debrillation should
domized
be per-
trials in this population.330
formed according to recommendations outlined in Sustained
the internation-
VT or VF, developing beyond the initial acute phase
al guidelines for cardiopulmonary resuscitation and (provided
emergency
the ventricular tachyarrhythmia is not due to a revers-
cardiovascular care.326,328 Even though it has been ibledemonstrated
cause, such as electrolyte disturbance or transient ischaemia/
that lidocaine can reduce the incidence of VF in thereinfarction),
acute phase are liable to recur and are associated with a high
of myocardial infarction, this drug increases the risk
riskofofasystole.
death. Although myocardial ischaemia should always be
A meta-analysis of 14 trials showed a trend towards ruledhigher
out inmortal-
case of ventricular arrhythmias, it should be empha-
ity in lidocaine-treated patients than in controls, which
sized that
is whyrevascularization is unlikely to prevent recurrent
routine prophylactic use of the drug is not justied.cardiac
329 In a arrest in patients with markedly abnormal LV function or
 2606 ESC Guidelines

sustained monomorphic VT, even if the original arrhythmia

spontaneously and rarely require intervention. AV block associated
appeared to result from transient ischaemia.331,332with Among survi-wall myocardial infarction is usually infra-Hisian, i.e.
anterior
vors of VF or sustained VT causing severe symptoms, ICD below the AV node, associated with an unstable, wide
located
therapy is associated with signicant mortality reduction,
QRS and com-low escape rhythm, and has a high mortality rate (up
pared with antiarrhythmic drug therapy (mainly amiodarone).
to 80%) due333 to the extensive myocardial necrosis. The develop-
With the exception of beta-blockers, antiarrhythmic drugs
ment of have
a new bundle branch block or hemiblock usually indicates
not shown to be effective as rst-line management extensive
of patientsanterior infarction. There is then a high likelihood of
with life-threatening ventricular arrhythmias and should not beboth a complete AV block and pump failure.
developing
used for the prevention of sudden death. An ICD is therefore
Asystole may follow AV block, bifascicular or trifascicular block,
recommended as secondary preventive therapy toor reduce mortal-
electrical countershock. If a pacing electrode is in place, pacing
ity in patients with signicant LV dysfunction, who present
should with
be attempted. Otherwise, chest compression and ventila-
haemodynamically unstable sustained VT or who are tionresuscitated
should be initiated, and transthoracic pacing started.
from VF that does not occur within the rst 2448 h.291A Suchtransvenous pacing electrode should be inserted in the pres-
patients should be subject to specialized electrophysiological
ence of advanced AV block with a low escape rhythm, as described
evaluation before discharge for placement of an implantable
above, and considered if bifascicular or trifascicular block develops.
cardioverter-debrillator (ICD) for secondary prevention of
The subclavian route should be avoided following brinolysis or in
sudden cardiac death.325,333 the presence of anticoagulation. Alternative sites should be chosen
Primary preventive ICD therapy has been shown to inreduce all-
this situation. Indications for pacing are outlined in detail in the
cause mortality in patients with reduced left ventricular ejection
ESC Guidelines for cardiac pacing and cardiac resynchronization
fraction (EF ,40%) as a result of an infarction that occurred
therapy.291 at Permanent pacing is indicated in patients with persist-
least 40 days earlier.333,334 In general, ICD implantation should
ent third-degree AV block, in patients with persistent second-
be deferred until at least 40 days after the acute event.
degree Evaluation
AV block associated with bundle branch block, and in tran-
of the need for a primary preventive ICD and implantation
sient Mobitzmay,II in
or complete heart block associated with new onset
some cases, be postponed until 3 months after revascularization
bundle branch block.291
procedures, to allow adequate time for recovery of LV function.
Patients may be evaluated for CRT and ICD treatment whenever
5.2Cardiac
stunning of viable myocardium can be excluded, indications for complications
which are outlined in guidelines.335 Certain demographic characteristics and procedural aspects dene
patients at higher risk for complications, who may require
extended monitoring. Advanced age, Killip II-IV symptoms,
3-vessel disease, anterior wall infarction, prolonged ischaemic
5.1.3.3 Sinus bradycardia and heart block
time or reduced TIMI ow are frequently cited. 213 Several mechan-
Sinus bradycardia is common in the rst hours of STEMI, espe-
ical complications may occur acutely in the rst days following
cially in inferior infarction. In some cases, opioids are responsible.
STEMI, although their incidence has fallen with the increase in
It often requires no treatment. If accompanied by severe hypoten-
the provision of prompt and effective reperfusion therapy. They
sion, sinus bradycardia should be treated by i.v. atropine, starting
are all life-threatening and need prompt detection and manage-
with a dosage of 0.250.5 mg, repeated up to a total of 1.5
ment. Repeated clinical examination (at least twice daily) may
2.0 mg. Occasionally it may be associated with hypotension at a
pick up a new cardiac murmur, suggestive of mitral regurgitation
later stage. If it then fails to respond to atropine, temporary
or ventricular septal defect, which then needs to be conrmed
pacing is advised.
or ruled out by immediate echocardiography. CABG should gener-
First-degree heart block needs no treatment.
ally be performed, if appropriate, at the time of surgery in patients
Second-degree Type I (Mobitz I or Wenckebach) atrioven-
requiring emergency surgery for serious mechanical complications.
tricular (AV) block is usually associated with inferior infarction
and seldom causes adverse haemodynamic effects. Should it do
5.2.1
so, however, atropine should be given rst. If this fails, Mitral valve regurgitation
pacing
Mitral
should be instituted. Agents that slow AV conduction (such valve
as regurgitation may occur during the subacute phase due
to LV
beta-blockers, digitalis, verapamil or amiodarone) should be dilatation, papillary muscle dysfunction or rupture of the tip
withheld. of the papillary muscle or chordae tendinae. It usually presents as
sudden
Second-degree Type II (Mobitz II) AV block and complete haemodynamic deterioration with acute dyspnoea and pul-
monary congestion
AV block may be indications for the insertion of a pacing electrode, and a new systolic murmur, which may be
certainly if bradycardia causes hypotension or heart underappreciated
failure. If the in this context. The diagnosis is suspected by
haemodynamic disturbance is severe, consideration clinical
should examination
be and should be immediately conrmed by
emergency
given to AV sequential pacing. Revascularization should always be echocardiography. Pulmonary oedema and cardiogenic
shock may
considered urgently in patients who have not yet received reperfu- occur rapidly. Treatment is based on afterload reduc-
sion therapy. tion to reduce regurgitant volume and pulmonary congestion, if
blood pressure
AV block associated with inferior wall infarction is usually supra- allows. Intravenous diuretic and vasodilator/ino-
tropic support,
Hisian, i.e. located above the His bundle, and associated with tran- as well as IABP, may stabilize patients in prepar-
ation
sient bradycardia with a narrow QRS escape rhythmabove 40 for angiography and surgery. Emergency surgical repair or
valve
beats per minuteand has low mortality. They usually resolve replacement is required. 337
ESC Guidelines 2607

5.2.2 Cardiac rupture pericardial rub may conrm the diagnosis but is often absent, espe-
Rupture of the LV free wall may occur during the subacute
cially withphasesubstantial pericardial effusion. Echocardiography will
following transmural infarction, and may present detect
as sudden and pain
quantify the size of effusion, if present, and rule out
and cardiovascular collapse with electromechanical haemorrhagic
dissociation.effusion with tamponade. The pain usually responds
The development of haemopericardium and tamponade to high-doseis usually
aspirin, paracetamol or colchicine. Steroids and long-
rapidly fatal. The diagnosis is conrmed by echocardiography.
term non-steroidal Sub- anti-inammatory drugs should be avoided due
acute free wall rupture, due to sealing of the site tobythe
thrombus
risk of scar
for- thinning with aneurysm development or rupture.
mation, if recognized, may permit time for pericardiocentesis
Pericardiocentesis and is rarely required, but should be performed in
immediate surgery. the presence of haemodynamic compromise with signs of tampon-
ade. When pericardial effusion is present, anticoagulant therapy, if
5.2.3 Ventricular septal rupture present (e.g. for prophylaxis of venous thrombo-embolism),
should beclinical
Ventricular septal rupture usually presents as rapid-onset interrupted unless absolutely indicated.
deterioration with acute heart failure and a loud systolic murmur
occurring during the subacute phase. The diagnosis is conrmed
by echocardiography, which will differentiate this5.2.6
from Left
acute ventricular aneurysm
mitral regurgitation and locate and quantify the rupture.
Patients338 Thea large transmural infarctionespecially of the an-
with
consequent left-to-right shunt may result in signsterolateral
and symptoms wallmay undergo infarct expansion with subsequent
of acute, new-onset right heart failure. An IABP may stabilize of LV aneurysm. This remodelling processof LV
development
patients in preparation for angiography and surgery. Intravenous
dilatation and aneurysm formation with volume overload
diuretics and vasodilators should be used with caution
resultsininhypoten-
combined systolic and diastolic dysfunction and, fre-
sive patients. Surgical repair is required urgently,quently,
but there is noregurgitation. Doppler echocardiography will
mitral
agreement on the optimal timing for surgery. 339 Early surgery
assess LV volume, is ejection fraction, the extent and degree of wall-
associated with a high mortality rate and a high risk of recurrent
motion abnormalities, and detect mural thrombus necessitating
ventricular rupture, while delayed surgery allows anticoagulation.
easier septal ACE inhibitors/ARBs and aldosterone antagonists
repair in scarred tissue but carries the risk of rupture
haveextension,
been shown to attenuate the remodelling process in trans-
tamponade and death while waiting for surgery. Mortality
mural infarction and improve survival, and should be administered
remains high in all patients and is higher in patients
earlywith inferobasal
following haemodynamic stabilization. Patients will frequently
defects as opposed to anteroapical location. develop the symptoms and signs of chronic heart failure and should
be treated according to guidelines for heart failure. 284
5.2.4 Right ventricular infarction
Right ventricular infarction may occur in isolation or, far more fre-
quently, in connection with inferior wall STEMI. It 5.2.7
frequently pre-
Left ventricular thrombus
sents with the triad of hypotension, clear lung elds and raised
The frequency of mural LV thrombus has decreased, largely
jugular venous pressure. Elevation of the ST-segment becausee1 mV in progress made in reperfusion therapy, the wide-
of the
V1 and V4R is suggestive of right ventricular infarction and
spread use of multiple antithrombotic agents in STEMI, and the
should routinely be sought in patients with inferior STEMI and
limitation of myocardial infarct size produced by effective, early
hypotension. Doppler echocardiography typically myocardial
demonstrates reperfusion.341,342 Although some studies suggest that
right ventricular dilatation, low pulmonary arterialup pressure,
to a quarter of anterior MIs have detectable LV thrombi, 343
dilated hepatic veins and varying degrees of inferior wall injury.
LV thrombi are associated with poor prognosis because of their as-
Despite the jugular distension, uid loading that maintains
sociationright with extensive infarcts, particularly anterior infarcts with
ventricular lling pressure is a key therapy in avoiding
apical orinvolvement,
treating and a risk of systemic embolism. Relatively old
hypotension. In addition, diuretics and vasodilators trials had be
should shown that anticoagulation in patients with large anterior
avoided, as they may aggravate hypotension. Maintenance
wall motionofabnormalities reduced the occurrence of mural
sinus rhythm and atrioventricular synchrony is important
thrombi.344346and Anticoagulation should therefore be considered
atrial brillation or atrioventricular block should beintreated
patients early.
with such large anterior wall motion abnormalities, if
they are at low risk of bleeding, to prevent the development of
5.2.5 Pericarditis thrombi. Consensus is that mural thrombi, once diagnosed,
The incidence of pericarditis after STEMI has decreased
requirewithoral the
anticoagulant therapy with vitamin K antagonists for
advent of modern, effective reperfusion therapy. 340 Pericarditis
up to 6 months. However, this has not been revisited in the era
manifests as recurrent chest pain, usually characteristically
of stenting sharp
and DAPT. Combining oral anticoagulation and DAPT
and, in contradistinction to recurrent ischaemia, related to therapy increases bleeding risks. The optimal duration
into a triple
posture and respiration. It may be associated withofST-segment
such triple antithrombotic therapy is unknown and should take
re-elevation. However, ST-segment re-elevation isintousually mildthe relative risks of bleeding and stent thrombosis.
account
and progressive, which helps distinguish it from the abrupt imaging of the left ventricle after 3 months of therapy
Repeated
ST-segment re-elevation seen in cases of coronary mayre-occlusion
allow discontinuation of anticoagulation earlier than 6
resulting from, for example, stent thrombosis. A continuous
months, if evidence of thrombus is no longer present, particularly
if there is recovery of apical wall motion.
 2608 ESC Guidelines

dening the optimal management strategy for non-culprit

6.Gaps in the evidence and areas
vessels in patients successfully treated with prior primary PCI
of the culprit artery.
for future research there is a need to dene the optimal long-term antithrombotic
regimen for patients receiving stents and who have an indication
There remain many important areas of uncertainty in forthe manage-
oral anticoagulants (e.g. due to high-risk atrial brillation,
ment of STEMI that offer opportunities for future research:
prosthetic heart valve or LV thrombus).
new antithrombotic agents in addition to aspirin and/or ADP re-
ceptor inhibitors have reduced ischaemic events, but with
increased
developing strategies to minimize early cardiac arrest may bebleeding risk. However, the optimal combination of
associated with large gains in survival. anticoagulant and antiplatelet therapies remains to be proven.
given
improving patients and public awareness of symptoms poten- the increased bleeding risk related to potent dual and
triple antithrombotic
tially related to STEMI and the need to call the EMS directly, therapy, it would be desirable to test
simpler
preferably via a unique centralized telephone number, is an combinations
im- and clarify the optimal duration of treat-
portant tool for shortening patient delay. ment for prevention of repeated ischaemic/thrombotic events.
in patients
investigating whether pre-hospital thrombolysis still has a role inwith known diabetes or acute hyperglycaemia, the
optimal
the management of patients seen early after symptom onset glucose management strategy in the acute and post-
discharge
and who otherwise have access to primary PCIis an important phases remains unclear, both in terms of optimal
medication
issue currently being tested in the ongoing Strategic Reperfusion choice and goals of therapy.
development
Early After Myocardial Infarction (STREAM) randomized clinical of percutaneous techniques for managing ven-
trial. tricular septal defects may permit avoidance or delay of surgical
while selected centres and geographic areas have made tremen-providing potentially life-saving therapy to these
repair, while
very
dous progress in ensuring high-quality rapid care for high-risk patients.
patients
the effectiveness
with STEMI, there remains a denite need for streamlining of and safety of cell therapy to replace myocar-
dium,
pre-hospital and hospital management, in order to shorten or minimize the consequences of myocardial injury,
needs
time to diagnosis and treatment in a homogeneous fashion to be established.
worldwide. Designing optimized clinical pathways the optimal therapeutic strategy to minimize risk of sudden
for ensuring
high-quality and homogeneous early STEMI diagnosis andin patients who develop VT or VF during or after
death
management at a national level is important. STEMI is not entirely clear.
more
reducing or minimizing myocardial injury and LV dysfunction evidence is needed on effective strategies to achieve and
maintain
following STEMI also remains a crucial goal. Several strategies long-term effective risk factor control.
are being tested, using a variety of pharmacological and
non-pharmacological approaches.

The CME text ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation is accredited by the European
Board for Accreditation in
Cardiology (EBAC). EBAC works according to the quality standards of the European Accreditation Council for Continuing Medical Education (EACCME), which is an
institution of
the European Union of Medical Specialists (UEMS). In compliance with EBAC/EACCME guidelines, all authors participating in this programme have disclosed any
potential conicts of
interest that might cause a bias in the article. The Organizing Committee is responsible for ensuring that all potential conicts of interest relevant to the
programme are declared to
the participants prior to the CME activities.
CME questions for this article are available at: European Heart Journal http://www.oxforde-learning.com/eurheartj and European Society of Cardiology
http://www.escardio.org/
guidelines. Badimon L, Bertrand M, Botker HE, Collet JP, Crea F, Danchin N, Falk E,
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