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OFFICIAL JOURNAL OF THE EUROPEAN ASSOCIATION
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Guidelines on myocardial revascularization
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EUROPEAN JOURNAL OF
CARDIO-THORACIC
SURGERY
Official Journal of the European Association for Cardio-Thoracic Surgery and
the European Society of Thoracic Surgeons
Contents
Vol. 38 Suppl. 1 (September 2010)
Cited in: Current Contents/Clinical Medicine — EMBASE/Excerpta Medica — MEDLINE/Index Medicus — Sociedad
Iberoamericana de Información Cientı́fica (SIIC)
Guidelines on myocardial revascularization
The Task Force on Myocardial Revascularization of the
European Society of Cardiology (ESC) and the
European Association for Cardio-Thoracic Surgery (EACTS)
EUROPEAN JOURNAL OF
CARDIO-THORACIC
SURGERY
Official Journal of the European Association for Cardio-Thoracic Surgery and
the European Society of Thoracic Surgeons
EDITOR-IN-CHIEF
Ludwig K. von Segesser, Lausanne, Switzerland
ASSOCIATE EDITORS
PAST EDITORS
Manuel J. Antunes, Coimbra, Portugal (Valves)
Jean Bachet, Abu Dhabi, United Arab Emirates
(Thoracic Vascular)
Friedhelm Beyersdorf, Freiburg, Germany (Cardiac
General)
Robert Dion, Genk, Belgium (Coronary)
Axel Haverich, Hannover, Germany (Transplantation)
Erino A. Rendina, Rome, Italy (Thoracic General)
Pascal A. Thomas, Marseille, France (ESTS)
Jarle Vaage, Oslo, Norway (Experimental)
René Prêtre, Zürich, Switzerland (Congenital)
Alexander Wahba, Trondheim, Norway (Perfusion)
David J. Wheatley, Glasgow, UK (CME)
Hans G. Borst, Hannover, Germany
Marko Turina, Zurich, Switzerland
EDITORIAL BOARD
Ottavio R. Alfieri, Milan, Italy
Hendrick B. Barner, St. Louis, USA
Eugene Baudet, Bordeaux-Pessac, France
John R. Benfield, Los Angeles, USA
Robert S. Bonser, Birmingham, UK
Thierry P. Carrel, Berne, Switzerland
David J. Chambers, London, UK
Joel Dunning, Middlesbrough, UK
Joachim Hasse, Freiburg, Germany
François Lacour-Gayet, New York, USA
Philippe Menasché, Paris, France
Enrico Ferrari, Lausanne, Switzerland
Hendrik T. Tevaearai, Berne, Switzerland
Bruno J. Messmer, Aachen, Germany
James L. Monro, Southampton, UK
Bernard H. Nachbur, Ittigen, Switzerland
José L. Pomar, Barcelona, Spain
José M. Revuelta, Santander, Spain
Paul Sergeant, Leuven, Belgium
Freyja-Maria Smolle-Jüttner, Graz, Austria
Gaetano Thiene, Padova, Italy
James A. Ch. Thorpe, Leeds, UK
Gus J. Vlahakes, Boston, USA
ASSISTANT EDITORS
Burkhardt Seifert (Statistical Consultant), Zurich, Switzerland
Denis Berdajs, Lausanne, Switzerland
MANAGING EDITOR
EDITORIAL MANAGER
Ian Beecroft
Judy Gaillard
Editorial Office EJCTS, av. Grand-St.-Bernard 69B (app. 6), CH-1920 Martigny (VS), Switzerland
Tel.: +41 27 7236171; fax: +41 27 7236173; e-mail: info@ejcts.ch
Supported by the Speciality Societies for Cardio-thoracic Surgery of Austria, Great Britain and Ireland, Italy, The Netherlands, Poland, Portugal,
Scandinavia, and Spain, the French Society of Thoracic and Cardiovascular Surgery, as well as the Belgian Society of Cardio-thoracic Surgery.
The primary aim of the European Journal of Cardio-thoracic Surgery is to provide a medium for the publication of high-quality material
documenting progress made in experimental advances relating to surgery. The journal publishes reports of significant clinical and experimental
advances relating to surgery of the heart, the great vessels and the chest. Special emphasis will be placed on contributions from European
countries.
European Journal of Cardio-thoracic Surgery 38, S1 (2010) S1 S52
www.elsevier.com/locate/ejcts
Guidelines on myocardial revascularization
The Task Force on Myocardial Revascularization of the
European Society of Cardiology (ESC) and the
European Association for Cardio-Thoracic Surgery (EACTS)
Developed with the special contribution of the
European Association for Percutaneous Cardiovascular Interventions (EAPCI)‡
Authors/Task Force Members: Philippe Kolh (Chairperson) (Belgium)*, William Wijns
(Chairperson) (Belgium)*, Nicolas Danchin (France), Carlo Di Mario (UK), Volkmar Falk
(Switzerland), Thierry Folliguet (France), Scot Garg (The Netherlands), Kurt Huber
(Austria), Stefan James (Sweden), Juhani Knuuti (Finland), Jose Lopez-Sendon (Spain),
Jean Marco (France), Lorenzo Menicanti (Italy), Miodrag Ostojic (Serbia), Massimo F.
Piepoli (Italy), Charles Pirlet (Belgium), Jose L. Pomar (Spain), Nicolaus Reifart (Germany),
Flavio L. Ribichini (Italy), Martin J. Schalij (The Netherlands), Paul Sergeant (Belgium),
Patrick W. Serruys (The Netherlands), Sigmund Silber (Germany), Miguel Sousa Uva
(Portugal), David Taggart (UK)
ESC Committee for Practice Guidelines: Alec Vahanian (Chairperson) (France), Angelo Auricchio (Switzerland), Jeroen Bax
(The Netherlands), Claudio Ceconi (Italy), Veronica Dean (France), Gerasimos Filippatos (Greece), Christian Funck-Brentano
(France), Richard Hobbs (UK), Peter Kearney (Ireland), Theresa McDonagh (UK), Bogdan A. Popescu (Romania), Zeljko Reiner
(Croatia), Udo Sechtem (Germany), Per Anton Sirnes (Norway), Michal Tendera (Poland), Panos E. Vardas (Greece), Petr
Widimsky (Czech Republic)
EACTS Clinical Guidelines Committee: Philippe Kolh (Chairperson) (Belgium), Ottavio Alfieri (Italy), Joel Dunning (UK), Stefano
Elia (Italy), Pieter Kappetein (The Netherlands), Ulf Lockowandt (Sweden), George Sarris (Greece), Pascal Vouhe (France)
Document Reviewers: Peter Kearney (ESC CPG Review Coordinator) (Ireland), Ludwig von Segesser (EACTS Review Coordinator)
(Switzerland), Stefan Agewall (Norway), Alexander Aladashvili (Georgia), Dimitrios Alexopoulos (Greece), Manuel J. Antunes
(Portugal), Enver Atalar (Turkey), Aart Brutel de la Riviere (The Netherlands), Alexander Doganov (Bulgaria), Jaan Eha
(Estonia), Jean Fajadet (France), Rafael Ferreira (Portugal), Jerome Garot (France), Julian Halcox (UK), Yonathan Hasin
(Israel), Stefan Janssens (Belgium), Kari Kervinen (Finland), Gunther Laufer (Austria), Victor Legrand (Belgium), Samer A.M.
Nashef (UK), Franz-Josef Neumann (Germany), Kari Niemela (Finland), Petros Nihoyannopoulos (UK), Marko Noc (Slovenia),
* Corresponding authors (the two chairpersons contributed equally to this document): Philippe Kolh, Cardiovascular Surgery Department,
University Hospital (CHU, ULg) of Liege, Sart Tilman B 35, 4000 Liege, Belgium. Tel: +32 4 366 7163, Fax: +32 4 366 7164, E-mail:
philippe.kolh@chu.ulg.ac.be
William Wijns, Cardiovascular Center, OLV Ziekenhuis, Moorselbaan 164, 9300 Aalst, Belgium. Tel: +32 53 724 439, Fax: +32 53 724 185, E-mail:
william.wijns@olvz-aalst.be
‡ Other ESC entities having participated in the development of this document:
Associations: Heart Failure Association (HFA), European Association for Cardiovascular Prevention and Rehabilitation (EACPR), European Heart
Rhythm Association (EHRA), European Association of Echocardiography (EAE).
Working Groups: Acute Cardiac Care, Cardiovascular Surgery, Thrombosis, Cardiovascular Pharmacology and Drug Therapy.
Councils: Cardiovascular Imaging, Cardiology Practice.
Disclaimer. The ESC Guidelines represent the views of the ESC and were 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 patient’s guardian or carer. It is also
the health professional’s responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.
1010-7940/$ see front matter © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
doi: 10.1016/j.ejcts.2010.08.019
S2
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Jan J. Piek (The Netherlands), Jan Pirk (Czech Republic), Yoseph Rozenman (Israel), Manel Sabate (Spain), Radovan Starc
(Slovenia), Matthias Thielmann (Germany), David J. Wheatley (UK), Stephan Windecker (Switzerland), Marian Zembala
(Poland)
The disclosure forms of the authors and reviewers are available on the ESC website www.escardio.org/guidelines
Keywords: Bare metal stents; Coronary artery bypass grafting; Coronary artery disease; Drug-eluting stents; EuroSCORE;
Guidelines; Heart team; Myocardial infarction; Myocardial ischaemia; Myocardial revascularization; Optimal medical therapy;
Percutaneous coronary intervention; Recommendation; Risk stratification; Stable angina; SYNTAX score; Unstable angina
Table of Contents
Abbreviations and acronyms . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3. Scores and risk stratification, impact of comorbidity . . . .
4. Process for decision making and patient information . . . .
4.1. Patient information . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2. Multidisciplinary decision making (Heart Team) . . .
5. Strategies for pre-intervention diagnosis and imaging . . .
5.1. Detection of coronary artery disease . . . . . . . . . . . .
5.2. Detection of ischaemia . . . . . . . . . . . . . . . . . . . . . . . .
5.3. Hybrid/combined imaging . . . . . . . . . . . . . . . . . . . . . .
5.4. Invasive tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.5. Prognostic value . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.6. Detection of myocardial viability . . . . . . . . . . . . . . .
6. Revascularization for stable coronary artery disease . . . .
6.1. Evidence basis for revascularization . . . . . . . . . . . . .
6.2. Impact of ischaemic burden on prognosis . . . . . . . .
6.3. Optimal medical therapy vs. percutaneous coronary
intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.4. Percutaneous coronary intervention with drugeluting stents vs. bare metal stents . . . . . . . . . . . . .
6.5. Coronary artery bypass grafting vs. medical therapy
6.6. Percutaneous coronary intervention vs. coronary
artery bypass grafting . . . . . . . . . . . . . . . . . . . . . . . . . .
6.7. Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7. Revascularization in non-ST-segment elevation acute
coronary syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.1. Intended early invasive or conservative strategies
7.2. Risk stratification . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.3. Timing of angiography and intervention . . . . . . . . . .
7.4. Coronary angiography, percutaneous coronary
intervention, and coronary artery bypass grafting .
7.5. Patient subgroups . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8. Revascularization in ST-segment elevation myocardial
infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.1. Reperfusion strategies . . . . . . . . . . . . . . . . . . . . . . . . .
8.1.1. Primary percutaneous coronary
intervention . . . . . . . . . . . . . . . . . . . . . . . . . .
8.1.2. Fibrinolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.1.3. Delayed percutaneous coronary
intervention . . . . . . . . . . . . . . . . . . . . . . . . . .
8.1.4. Coronary artery bypass grafting . . . . . . . . .
8.2. Cardiogenic shock and mechanical complications .
8.2.1. Cardiogenic shock . . . . . . . . . . . . . . . . . . . . . .
8.2.2. Mechanical complications . . . . . . . . . . . . . . .
8.2.3. Circulatory assistance . . . . . . . . . . . . . . . . . .
9. Special conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9.1. Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9.1.1. Indications for myocardial revascularization
9.1.2. Type of intervention: coronary artery
bypass grafting vs. percutaneous coronary
intervention . . . . . . . . . . . . . . . . . . . . . . . . . .
9.1.3. Specific aspects of percutaneous coronary
intervention . . . . . . . . . . . . . . . . . . . . . . . . . .
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9.1.4. Type of coronary artery bypass grafting
intervention . . . . . . . . . . . . . . . . . . . . . . . . . .
9.1.5. Antithrombotic pharmacotherapy . . . . . . . .
9.1.6. Antidiabetic medications . . . . . . . . . . . . . . .
9.2. Myocardial revascularization in patients with
chronic kidney disease . . . . . . . . . . . . . . . . . . . . . . . . .
9.3. Myocardial revascularization in patients requiring
valve surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9.4. Associated carotid/peripheral arterial disease . . . .
9.4.1. Associated coronary and carotid artery
disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9.4.2. Associated coronary and peripheral arterial
disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9.5. Myocardial revascularization in chronic heart failure
9.6. Crossed revascularization procedures . . . . . . . . . . . .
9.6.1. Revascularization for acute graft failure . .
9.6.2. Revascularization for late graft failure . . .
9.6.3. Revascularization for acute failure after
percutaneous coronary intervention . . . . .
9.6.4. Elective revascularization for late failure
after percutaneous coronary intervention
9.6.5. Hybrid procedures . . . . . . . . . . . . . . . . . . . . .
9.7. Arrhythmias in patients with ischaemic
heart disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9.7.1. Atrial fibrillation . . . . . . . . . . . . . . . . . . . . . . .
9.7.2. Supraventricular arrhythmias other than
atrial fibrillation or flutter . . . . . . . . . . . . . .
9.7.3. Ventricular arrhythmias . . . . . . . . . . . . . . . .
9.7.4. Concomitant revascularization in heart
failure patients who are candidates for
resynchronization therapy . . . . . . . . . . . . . .
10. Procedural aspects of coronary artery bypass grafting . .
10.1. Pre-operative management . . . . . . . . . . . . . . . . . . . . .
10.2. Surgical procedures . . . . . . . . . . . . . . . . . . . . . . . . . . .
10.2.1. Coronary vessel . . . . . . . . . . . . . . . . . . . . . . . .
10.2.2. Bypass graft . . . . . . . . . . . . . . . . . . . . . . . . . . .
10.3. Early post-operative risk . . . . . . . . . . . . . . . . . . . . . . .
11. Procedural aspects of percutaneous coronary intervention
11.1. Impact of clinical presentation . . . . . . . . . . . . . . . . .
11.2. Specific lesion subsets . . . . . . . . . . . . . . . . . . . . . . . . .
11.3. Drug-eluting stents . . . . . . . . . . . . . . . . . . . . . . . . . . . .
11.4. Adjunctive invasive diagnostic tools . . . . . . . . . . . . .
12. Antithrombotic pharmacotherapy . . . . . . . . . . . . . . . . . . . . .
12.1. Elective percutaneous coronary intervention . . . . .
12.2. Non-ST-segment elevation acute coronary syndrome
12.3. ST-segment elevation myocardial infarction . . . . . .
12.4. Points of interest and special conditions . . . . . . . .
13. Secondary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
13.1. Background and rationale . . . . . . . . . . . . . . . . . . . . . .
13.2. Modalities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
13.3. Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
14. Strategies for follow-up . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Abbreviations and acronyms
ACC
ACE
ACEF
ACS
AF
AHA
AHF
AMI
aPTT
ASA
BiVAD
BMI
BMS
BTT
CABG
CAD
CAS
CEA
CHADS2
CHF
CI
CIN
CKD
CPB
CRT
CT
CTO
CVA
DAPT
DES
DT
EACTS
EBAC
ECG
ECMO
EF
EMS
ESC
ESRD
FFR
FMC
GFR
GIK
GP
GPIIb IIIa
HF
HR
IABP
ICD
ICU
ITA
i.v.
IVUS
LA
American College of Cardiology
angiotensin-converting enzyme
age, creatinine, ejection fraction
acute coronary syndrome
atrial fibrillation
American Heart Association
acute heart failure
acute myocardial infarction
activated partial thromboplastin time
acetylsalicylic acid
biventricular assist device
body mass index
bare metal stent
bridge to transplantation
coronary artery bypass grafting
coronary artery disease
carotid artery stenting
carotid endarterectomy
CHF, hypertension, age, diabetes, stroke
chronic heart failure
confidence interval
contrast-induced nephropathy
chronic kidney disease
cardiopulmonary bypass
cardiac resynchronization therapy
computed tomography
chronic total occlusion
cerebrovascular accident
dual antiplatelet therapy
drug-eluting stent
destination therapy
European Association for Cardio-Thoracic Surgery
European Board for Accreditation in Cardiology
electrocardiogram
extracorporeal membrane oxygenator
ejection fraction
emergency medical service
European Society of Cardiology
end stage renal disease
fractional flow reserve
first medical contact
glomerular filtration rate
glucose insulin potassium
general physician
glycoprotein IIb IIIa
heart failure
hazard ratio
intra-aortic balloon pump
implantable cardioverter defibrillator
intensive care unit
internal thoracic artery
intravenous
intravascular ultrasound
left atrium
LAD
LCx
LM
LMWH
LV
LVAD
LVEF
MACCE
MACE
MDCT
MI
MIDCAB
MPS
MR
MRI
MVD
NCDR
NPV
NSTE-ACS
NYHA
OCT
OMT
OR
PAD
PCI
PES
PET
PPV
RCA
RCT
s.c.
SCD
SES
SPECT
STEMI
SVG
SVR
TIA
TVR
UFH
VD
VSD
VT
ZES
S3
left anterior descending
left circumflex
left main
low molecular weight heparin
left ventricle
left ventricular assist device
left ventricular ejection fraction
major adverse cardiac and cerebral event
major adverse cardiac event
multidetector computed tomography
myocardial infarction
minimally invasive direct coronary artery bypass
myocardial perfusion stress
mitral regurgitation
magnetic resonance imaging
multivessel disease
National Cardiovascular Database Registry
negative predictive value
non-ST-segment elevation acute coronary
syndrome
New York Heart Association
optical coherence tomography
optimal medical therapy
odds ratio
peripheral arterial disease
percutaneous coronary intervention
paclitaxel-eluting stent
positron emission tomography
positive predictive value
right coronary artery
randomized clinical trial
subcutaneous
sudden cardiac death
sirolimus-eluting stent
single photon emission computed tomography
ST-segment elevation myocardial infarction
saphenous vein graft
surgical ventricular reconstruction
transient ischaemic attack
target vessel revascularization
unfractionated heparin
vessel disease
ventricular septal defect
ventricular tachycardia
zotarolimus-eluting stent
1. Preamble
Guidelines and Expert Consensus Documents summarize and
evaluate all available evidence with the aim of assisting
physicians in selecting the best management strategy for an
individual patient suffering from a given condition, taking
into account the impact on outcome and the risk benefit
ratio of diagnostic or therapeutic means. Guidelines are no
substitutes for textbooks and their legal implications have
been discussed previously. Guidelines and recommendations
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
should help physicians to make decisions in their daily
practice. However, the ultimate judgement regarding the
care of an individual patient must be made by his/her
responsible physician(s).
The recommendations for formulating and issuing ESC
Guidelines and Expert Consensus Documents can be found
on the ESC website (http://www.escardio.org/knowledge/
guidelines/rules).
Members of this Task Force were selected by the European
Society of Cardiology (ESC) and the European Association for
Cardio-Thoracic Surgery (EACTS) to represent all physicians
involved with the medical and surgical care of patients
with coronary artery disease (CAD). A critical evaluation
of diagnostic and therapeutic procedures is performed
including assessment of the risk benefit ratio. Estimates
of expected health outcomes for society are included,
where data exist. The level of evidence and the strength
of recommendation of particular treatment options are
weighed and graded according to predefined scales, as
outlined in Tables 1 and 2.
The members of the Task Force have provided disclosure
statements of all relationships that might be perceived as
real or potential sources of conflicts of interest. These
disclosure forms are kept on file at European Heart House,
headquarters of the ESC. Any changes in conflict of interest
that arose during the writing period were notified to the ESC.
The Task Force report received its entire financial support
from the ESC and EACTS, without any involvement of the
pharmaceutical, device, or surgical industry.
ESC and EACTS Committees for Practice Guidelines are
responsible for the endorsement process of these joint
Guidelines. The finalized document has been approved by all
the experts involved in the Task Force, and was submitted to
outside specialists selected by both societies for review. The
document is revised, and finally approved by ESC and EACTS
Table 1
Classes of recommendations
Classes of
recommendations
Definition
Class I
Evidence and/or general agreement that a given
treatment or procedure is beneficial, useful,
effective.
Conflicting evidence and/or a divergence of opinion
about the usefulness/efficacy of the given treatment
or procedure.
Weight of evidence/opinion is in favour of
usefulness/efficacy.
Usefulness/efficacy is less well established by
evidence/opinion.
Evidence or general agreement that the given
treatment or procedure is not useful/effective, and
in some cases may be harmful.
Class II
Class IIa
Class IIb
Class III
Table 2
Levels of evidence
Level of evidence A
Level of evidence B
Level of evidence C
Data derived from multiple randomized clinical
trials or meta-analyses.
Data derived from a single randomized clinical
trial or large non-randomized studies.
Consensus of opinion of the experts and/or
small studies, retrospective studies, registries.
and subsequently published simultaneously in the European
Heart Journal and the European Journal of Cardio-Thoracic
Surgery.
After publication, dissemination of the Guidelines is of
paramount importance. Pocket-sized versions and personal
digital assistant-downloadable versions are useful at the
point of care.
Some surveys have shown that the intended users are
sometimes unaware of the existence of guidelines, or simply
do not translate them into practice. Thus, implementation
programmes are needed because it has been shown that
the outcome of disease may be favourably influenced by the
thorough application of clinical recommendations.
2. Introduction
Myocardial revascularization has been an established
mainstay in the treatment of CAD for almost half a century.
Coronary artery bypass grafting (CABG), used in clinical
practice since the 1960s, is arguably the most intensively
studied surgical procedure ever undertaken, while percutaneous coronary intervention (PCI), used for over three
decades, has been subjected to more randomized clinical
trials (RCTs) than any other interventional procedure. PCI
was first introduced in 1977 by Andreas Gruentzig and by the
mid-1980s was promoted as an alternative to CABG. While
both interventions have witnessed significant technological
advances, in particular the use of drug-eluting stents (DES) in
PCI and of arterial grafts in CABG, their role in the treatment
of patients presenting with stable CAD is being challenged
by advances in medical treatment, referred to as optimal
medical therapy (OMT), which include intensive lifestyle and
pharmacological management. Furthermore, the differences
between the two revascularization strategies should be
recognized. In CABG, bypass grafts are placed to the midcoronary vessel beyond the ‘culprit’ lesion(s), providing
extra sources of nutrient blood flow to the myocardium
and offering protection against the consequences of further
proximal obstructive disease. In contrast, coronary stents
aim to restore the normal conductance of the native
coronary vasculature without offering protection against
new disease proximal to the stent.
Even with this fundamental difference in the mechanisms of action between the two techniques, myocardial
revascularization provides the best results when focusing
on the relief of ischaemia. In patients presenting with
unstable angina, non-ST-segment elevation acute coronary
syndrome (NSTE-ACS), and ST-segment elevation myocardial
infarction (STEMI), myocardial ischaemia is obvious and lifethreatening. Culprit coronary stenoses are easily identified
by angiography in the vast majority of cases. By contrast,
in patients with stable CAD and multivessel disease (MVD) in
particular, identification of the culprit stenosis or stenoses
requires anatomical orientation by angiography combined
with functional evaluation, obtained either by non-invasive
imaging before catheterization, or during the invasive
procedure using pressure-derived fractional flow reserve
(FFR) measurements.
Many conditions, stable or acute, can be treated in
different ways, including PCI or surgical revascularization.
The advances in technology imply that most coronary
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 3
Recommended risk stratification scores to be used in candidates for percutaneous coronary intervention or coronary artery bypass grafting
Score
Calculation
Number of variables
used to calculate risk
Clinical
Angiographic
EuroSCORE
SYNTAX score
www.euroscore.org/calc.html
www.syntaxscore.com
17
0
0
11 (per lesion)
Mayo Clinic Risk Score
NCDR CathPCI
Parsonnet score
STS score d
[7,8]
[5]
[9]
http://209.220.160.181/
STSWebRiskCalc261/
7
8
16
40
0
0
0
2
ACEF score
[Age/ejection fraction (%)] + 1
(if creatinine >2 mg/dL) [11]
2
0
Validated outcomes
Short- and long-term mortality
Quantify coronary artery disease
complexity
MACE and procedural death
In-hospital mortality
30-day mortality
Operative mortality, stroke, renal
failure, prolonged ventilation, deep
sternal infection, re-operation,
morbidity, length of stay <6 or >14
days
Mortality in elective CABG
Class a / Level b
PCI
CABG
IIb B
IIa B
IB
III B
IIb C
IIb B
III C
III B
IB
Ref. c
[2,3,6]
[4]
[5]
[9]
[10]
IIb C
a
Class of recommendation.
Level of evidence.
References.
d
The STS score is undergoing periodic adjustement which makes longitudinal comparisons difficult.
ACEF = age, creatinine, ejection fraction; CABG = coronary artery bypass grafting; MACE = major adverse cardiac event; NCDR = National Cardiovascular
Database Registry; PCI = percutaneous coronary intervention; STS = Society of Thoracic Surgeons.
b
c
lesions are technically amenable to PCI; however, technical
feasibility is only one element of the decision-making
process, which should incorporate clinical presentation,
severity of angina, extent of ischaemia, response to medical
therapy, and extent of anatomical disease by angiography.
Both revascularization methods carry procedure-related
risks that are different to some extent in nature, rate,
and time domain. Thus patients and physicians need to
‘balance short-term convenience of the less invasive PCI
procedure against the durability of the more invasive
surgical approach’ [1].
Formulation of the best possible revascularization approach, taking into consideration the social and cultural
context also, will often require interaction between
cardiologists and cardiac surgeons, referring physicians or
other specialists as desirable. Patients need help in taking
informed decisions about their treatment, and the most
valuable advice will likely be provided to them by the
Heart Team. Recognizing the importance of the interaction
between (interventional) cardiologists and cardiac surgeons,
the leadership of both the ESC and EACTS has given this Joint
Task Force, their respective Guideline Committee, and the
reviewers of this document the mission to draft balanced,
patient-centred, evidence-driven practice guidelines on
myocardial revascularization.
3. Scores and risk stratification, impact of
comorbidity
Myocardial revascularization is appropriate when the
expected benefits, in terms of survival or health outcomes
(symptoms, functional status, and/or quality of life), exceed
the expected negative consequences of the procedure.
Therefore, risk assessment is an important aspect of
contemporary clinical practice, being of value to clinicians
and patients. Over the long term, it allows quality control
and the assessment of health economics, while also serving
as a means for individual operators, institutions and
regulatory bodies to assess and compare performance.
Numerous different models have been developed for
risk stratification, and those in current clinical use are
summarized in Table 3. Comparative analyses of these
models are limited because available studies have largely
evaluated individual risk models in different patient
populations with different outcome measures reported at
various time points. These limitations restrict the ability to
recommend one specific risk model; however:
• The EuroSCORE validated to predict surgical mortality
was recently shown to be an independent predictor of
major adverse cardiac events (MACEs) in studies with
both percutaneous and surgical treatment arms [2,3].
Therefore, it can be used to determine the risk of
revascularization irrespective of, and even before, the
selection of treatment strategy. It has little role, however,
in determining optimal treatment.
• The SYNTAX score has been shown to be an independent
predictor of MACE in patients treated with PCI but not with
CABG [4]. Therefore it has a role in aiding the selection of
optimal treatment by identifying those patients at highest
risk of adverse events following PCI.
• The National Cardiovascular Database Registry (NCDR
CathPCI risk score) has been validated in PCI patients and
should only be used in this context [5].
• The Society of Thoracic Surgeons (STS) score, and the age,
creatinine, and ejection fraction (ACEF) score have been
validated in surgical patients, and therefore should only
be used to determine surgical risk.
It is important to acknowledge that no risk score can
accurately predict events in an individual patient. Moreover,
limitations exist with all databases used to build risk models,
and differences in definitions and variable content can
affect the performance of risk scores when they are applied
across different populations. Ultimately risk stratification
should be used as a guide, while clinical judgement and
multidisciplinary dialogue (Heart Team) remain essential.
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Table 4
Multidisciplinary decision pathways, patient informed consent, and timing of intervention
ACS
Stable MVD
Stable with
indication for
ad hoc PCI a
Required.
Required.
Written informed
consent d .
Written informed
consent d .
According to
predefined
protocols.
Written informed
consent d .
Urgency: time constraints
apply.
Elective:
no time constraints.
Elective:
no time constraints.
Proceed with intervention
based on best evidence/
availability. Non-culprit
lesions treated according
to institutional protocol.
Plan most
appropriate
intervention
allowing enough
time from
diagnostic
catheterization
to intervention.
Proceed with
intervention
according to
institutional
protocol defined by
local Heart Team.
Shock
STEMI
NSTE-ACS b
Other ACS c
Multidisciplinary
decision making
Not mandatory.
Not mandatory.
Informed
consent
Oral witnessed
informed consent
or family consent
if possible without
delay.
Time to
revascularization
Emergency:
no delay.
Oral witnessed
informed consent
may be sufficient
unless written
consent is legally
required.
Emergency:
no delay.
Not required for culprit
lesion but required for
non-culprit vessel(s).
Written informed
consent d (if time
permits).
Procedure
Proceed with
intervention
based on best
evidence/
availability.
Proceed with
intervention
based on best
evidence/
availability.
Urgency: within 24 h if
possible and no later
than 72 h.
Proceed with
intervention
based on best
evidence/availability.
Non-culprit lesions
treated according to
institutional protocol.
a
Potential indications for ad hoc PCI are listed in Table 5.
See also Table 12.
Other ACS refers to unstable angina, with the exception of NSTE-ACS.
d
This may not apply to countries that legally do not ask for written informed consent. ESC and EACTS strongly advocate documentation of patient consent for
all revascularization procedures.
ACS = acute coronary syndrome; MVD = multivessel disease; NSTE-ACS = non-ST-segment elevation acute coronary syndrome; PCI = percutaneous coronary
intervention; STEMI = ST-segment elevation myocardial infarction.
b
c
4. Process for decision making and patient
information
4.1. Patient information
Patient information needs to be objective and unbiased,
patient oriented, evidence based, up-to-date, reliable,
understandable, accessible, relevant, and consistent with
legal requirements. Informed consent requires transparency,
especially if there is controversy about the indication for a
particular treatment (PCI vs. CABG vs. OMT). Collaborative
care requires the preconditions of communication, comprehension, and trust. It is essential to realize that health care
decisions can no longer be based solely on research results
and our appraisal of the patient’s circumstances. Patients
taking an active role throughout the decision making process
have better outcomes. However, most patients undergoing
CABG or PCI have limited understanding of their disease
and sometimes unreasonable expectations with regard to
the proposed intervention, its complications, or the need
for late reintervention, especially after PCI.
Informing patients about treatment choices allows them
to reflect on the advantages and disadvantages associated
with either strategy. Patients can only weigh this information
properly in the light of their personal values and must have
the time to reflect on the trade-offs imposed by the estimates. The patient deserves to fully understand the risks,
benefits, and uncertainties associated with the condition
and its treatment. Avoiding incomprehensible jargon, and
consistent use of terminology that the patient understands,
are mandatory. Informed medical decision making should
consider short-term procedure-related benefits and risks as
well as expected long-term risks and benefits in terms of
survival, relief of angina, quality of life, and the potential
need for late reintervention. It is equally important that
any bias of stakeholders towards various treatment options
for CAD is made known to the patient. Specialty bias and
self-referral should not interfere with the decision process.
With the exception of unstable patients or candidates for
ad hoc PCI (Table 4), the patient should be offered enough
time, up to several days as required, between diagnostic
catheterization and intervention to reflect on the results of
the diagnostic angiogram, to seek a second opinion as desirable, or to discuss the findings and consequences with his or
her referring cardiologist and/or primary care physician. An
example of a suitable and balanced patient information document is provided in the Appendix of the online document.
There is growing public demand for transparency regarding
site and operator results. Anonymous treatment should be
avoided. It is the patient’s right to know who is about to
treat him or her and to obtain information on the level
of expertise of the operator and the volume load of the
centre. In addition, the patient should be informed whether
all treatment options are available at the site and whether
surgery is offered on site or not. Non-emergent high-risk
PCI procedures, including those performed for distal left
main (LM) disease, complex bifurcation stenosis involving
large side branches, single remaining coronary artery, and
complex chronic total occlusion (CTO) recanalization, should
be performed by adequately experienced operators at
centres that have access to circulatory support and intensive
care treatment, and have cardiovascular surgery on site.
For patients with stable CAD and multivessel or LM
disease, all relevant data should be reviewed by a
clinical/non-invasive cardiologist, a cardiac surgeon, and
an interventional cardiologist (Heart Team) to determine
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
the likelihood of safe and effective revascularization with
either PCI or CABG [4]. To ensure this review, myocardial
revascularization should in general not be performed at the
time of diagnostic angiography, thereby allowing the Heart
Team sufficient time to assess all available information,
reach a consensus, and clearly explain and discuss the
findings with the patient. Standard evidence-based interdisciplinary institutional protocols may be used for common
case scenarios, but complex cases should be discussed
individually to find the best solution for each patient.
The above obviously pertains to patients in a stable
condition who can make a decision without the constraints
of an emergency situation. If potential adverse events are
negligible compared with the expected treatment benefit
or there is no viable alternative to emergency treatment,
informed decision making may not be possible.
Patients considered for revascularization should also be
clearly informed of the continuing need for OMT including
antiplatelet agents, statins, b-blockers, and angiotensinconverting enzyme (ACE) inhibitors, as well as other
secondary prevention strategies (Section 13).
Table 5
Potential indications for ad hoc percutaneous coronary intervention vs.
revascularization at an interval
4.2. Multidisciplinary decision making
(Heart Team)
Table 6
Recommendations for decision making and patient information
The process for medical decision making and patient information is guided by the ‘four principles’ approach to healthcare ethics: autonomy, beneficience, non-maleficience, and
justice. The informed consent process should therefore not
be looked at solely as a necessary legal requirement but
should be used as an opportunity to optimize objective
decision making. Awareness that other factors such as sex,
race, availability, technical skills, local results, referral
patterns, and patient preference, which sometimes contradict evidentiary best practice, may have an impact on the
decision making process, independently of clinical findings,
is mandatory. The creation of a Heart Team serves the
purpose of a balanced multidisciplinary decision process [4].
Additional input may be needed from general practitioners,
anaesthesiologists, geriatricians, or intensivists. Hospital
teams without a cardiac surgical unit or with interventional
cardiologists working in an ambulatory setting should
refer to standard evidence-based protocols designed in
collaboration with an expert interventional cardiologist and
a cardiac surgeon, or seek their opinion for complex cases.
Consensus on the optimal revascularization treatment should
be documented. Standard protocols compatible with the current Guidelines may be used to avoid the need for systematic
case-by-case review of all diagnostic angiograms.
Ad hoc percutaneous coronary intervention
Ad hoc PCI is defined as a therapeutic interventional
procedure performed immediately (with the patient still on
the catheterization table) following the diagnostic procedure as opposed to a staged procedure performed during a
different session. Ad hoc PCI is convenient for the patient,
associated with fewer access site complications, and often
Ad hoc PCI
Haemodynamically unstable patients (including cardiogenic shock).
Culprit lesion in STEMI and NSTE-ACS.
Stable low-risk patients with single or double vessel disease (proximal LAD
excluded) and favourable morphology (RCA, non-ostial LCx, mid- or distal
LAD).
Non-recurrent restenotic lesions.
Revascularization at an interval
Lesions with high-risk morphology.
Chronic heart failure.
Renal failure (creatinine clearance <60 mL/min), if total contrast volume
required >4 mL/kg.
Stable patients with MVD including LAD involvement.
Stable patients with ostial or complex proximal LAD lesion.
Any clinical or angiographic evidence of higher periprocedural risk with
ad hoc PCI.
LAD = left anterior descending; LCx = left circumflex; MVD = multivessel
disease; NSTE-ACS = non-ST-segment elevation acute coronary syndrome;
PCI = percutaneous coronary intervention; RCA = right coronary artery;
STEMI = ST-segment elevation myocardial infarction.
It is recommended that patients be adequately informed
about the potential benefits and short- and long-term
risks of a revascularization procedure. Enough time
should be spared for informed decision making.
The appropriate revascularization strategy in patients
with MVD should be discussed by the Heart Team.
Class a
Level b
I
C
I
C
a
Class of recommendation.
Level of evidence.
MVD = multivessel disease.
b
cost-effective. However, in a review of >38 000 patients
undergoing ad hoc PCI, 30% of patients were in categories
that were regarded as potential candidates for CABG.
Ad hoc PCI is therefore reasonable for many patients,
but not desirable for all, and should not automatically
be applied as a default approach. Institutional protocols
designed by the Heart Team should be used to define
specific anatomical criteria and clinical subsets that can or
cannot be treated ad hoc. Based on resources and settings,
geographical differences can be expected. Table 5 lists
potential indications for ad hoc PCI. All other pathologies
in stable patients, including lesions of the LM or proximal
left anterior descending (LAD) artery and MVD involving the
LAD artery, should be discussed by a Heart Team before a
deferred revascularization procedure (PCI or CABG). Table 6
lists the recommendations for decision making and patient
information.
5. Strategies for pre-intervention
diagnosis and imaging
Exercise testing and cardiac imaging are used to confirm
the diagnosis of CAD, to document ischaemia in patients
with stable symptoms, to risk stratify patients with stable
angina and an acute coronary syndrome (ACS), and to
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 7
Indications of different imaging tests for the diagnosis of obstructive coronary artery disease and for the assessment of prognosis in subjects without
known coronary artery disease a
Asymptomatic
(screening)
Anatomical test
Invasive angiography
MDCT angiography
MRI angiography
Functional test
Stress echo
Nuclear imaging
Stress MRI
PET perfusion
Symptomatic
Pretest likelihood b of obstructive disease
Low
Intermediate
High
III A
III B c
III B
III A
IIb B
III B
IIb A
IIa B
III B
IA
III B
III B
III
III
III
III
III
III
III
III
IA
IA
IIa B
IIa B
III
III
III
III
A
A
B
B
A
A
C
C
Ad
Ad
Bd
Bd
Prognostic value of
positive result a
Prognostic value of
negative result a
References
IA
IIb B
III C
IA
IIa B
III C
[12]
[17 20]
[22]
IA
IA
IIa B
IIa B
IA
IA
IIa B
IIa B
[12]
[12]
[12,23 25]
[26]
a
For the prognostic assessment of known coronary stenosis, functional imaging is similarly indicated.
The pretest likelihood of disease is calculated based on symptoms, sex, and risk factors.
c
This refers to MDCT angiography, not calcium scoring.
d
In patients with obstructive CAD documented by angiography, functional testing may be useful in guiding the revascularization strategy based on the extent,
severity, and localisation of ischaemia.
CAD = coronary artery disease; MDCT = multidetector computed tomography; MRI = magnetic resonance imaging; PET = positron emission tomography.
b
help choose treatment options and evaluate their efficacy.
In practice, diagnostic and prognostic assessments are
conducted in tandem rather than separately, and many of
the investigations used for diagnosis also offer prognostic
information [12]. In elective cases, the pre-test likelihood
of disease is calculated based on symptoms, sex, and
risk factors. Patients with an intermediate likelihood of
obstructive CAD will undergo exercise testing while patients
with a high likelihood undergo direct invasive examination.
Boundaries defining intermediate likelihood of CAD are
usually set at 10 90% or 20 80%. Because of high availability
and low costs, an exercise electrocardiogram (ECG) is
the most commonly used test to confirm the anginal
nature of the symptoms and to provide objective evidence
of inducible ischaemia. Its accuracy is limited however,
especially in women [12]. Many of the patients with
an intermediate likelihood of CAD post-exercise ECG are
reclassified into higher or lower likelihood groups after noninvasive functional imaging.
The target of revascularization therapy is myocardial
ischaemia, not the epicardial coronary disease itself.
Revascularization procedures performed in patients with
documented ischaemia reduce total mortality [13] through
reduction of ischaemic burden [14]. Discrepancies between
the apparent anatomical severity of a lesion and its
functional effects on myocardial blood supply are common,
especially in stable CAD. Thus, functional assessment, noninvasive or invasive, is essential for intermediate stenoses.
Revascularization of lesions without functional significance
can be deferred [15].
Another indication for non-invasive imaging before
revascularization is the detection of myocardial viability
in patients with poor left ventricle (LV) function. Patients
who have viable but dysfunctional myocardium are at
higher risk if not revascularized, while the prognosis of
patients without viable myocardium is not improved by
revascularization [16,17].
The current evidence supporting the use of various tests
for the detection of CAD is based on meta-analyses and
multicentre studies (Table 7). Few RCTs have assessed health
outcomes for diagnostic testing and the available evidence
has been derived largely from non-randomized studies. On
many occasions the choice of the test is based on local
expertise and availability of the test. Although several tests
can be used, it is important to avoid unnecessary diagnostic
steps.
When considering any test to detect CAD one must
also take into account the risks associated with the test
itself. The risks of exercise, pharmacological stressors,
contrast agents, invasive procedures, and cumulative
ionizing radiation must be weighed against the risk of disease
or delayed diagnosis.
In summary, documentation of ischaemia using functional
testing is strongly recommended before elective invasive
procedures, preferably using non-invasive testing before
invasive angiography.
5.1. Detection of coronary artery disease
There are two non-invasive angiographic techniques that can
directly image coronary arteries: multidetector computed
tomography (MDCT) and magnetic resonance imaging (MRI).
Multidetector computed tomography coronary
angiography
The studies and meta-analyses of MDCT to detect CAD
have generally shown high negative predictive values (NPVs),
suggesting that MDCT is excellent in excluding significant
CAD [18,19], while positive predictive values (PPVs) were
only moderate. In the two multicentre trials published, one
was consistent with the results of prior meta-analyses [20]
but the other showed only moderate NPV (83 89%) [21]. Only
about half of the stenoses classified as significant by MDCT
are associated with ischaemia [22] indicating that MDCT
angiography cannot accurately predict the haemodynamic
significance of coronary stenosis.
In summary, MDCT is reliable for ruling out significant
CAD in patients with stable and unstable anginal syndromes
and in patients with low to moderate likelihood of CAD.
However, MDCT angiography typically overestimates the
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
severity of atherosclerotic obstructions and decisions for
patient management require further functional testing.
Magnetic resonance imaging coronary angiography
Data suggest that MRI coronary angiography has a lower
success rate and is less accurate than MDCT for the detection
of CAD [18].
5.2. Detection of ischaemia
The tests are based on either reduction of perfusion
or induction of ischaemic wall motion abnormalities
during exercise or pharmacological stress. The most wellestablished stress imaging techniques are echocardiography
and perfusion scintigraphy. Both may be used in combination
with either exercise stress or pharmacological stress.
Newer stress imaging techniques also include stress MRI,
positron emission tomography (PET) imaging, and combined
approaches. The term hybrid imaging refers to imaging
systems in which two modalities [MDCT and PET, MDCT and
single photon emission computed tomography (SPECT)] are
combined in the same scanner, allowing both studies to be
performed in a single imaging session.
Stress imaging techniques have several advantages over
conventional exercise ECG testing, including superior
diagnostic performance [12], the ability to quantify and
localize areas of ischaemia, and the ability to provide
diagnostic information in the presence of resting ECG
abnormalities or when the patient is unable to exercise.
For these reasons, stress imaging techniques are preferred
in patients with previous PCI or CABG. In patients with
angiographically confirmed intermediate coronary lesions,
evidence of ischaemia is predictive of future events.
Stress echocardiography
Stress echocardiography is an established diagnostic test
and is more accurate than exercise ECG test in the detection
of ischaemia [12].
The most frequently used method is a physical exercise
test typically using a bicycle ergometer, but pharmacological
stressors such as dobutamine and less frequently dipyridamole can also be used. The technique requires adequate
training and experience since it is more user dependent than
other imaging techniques. Pooled sensitivity and specificity
of exercise echocardiography are reported as 80 85% and
84 86%, respectively [12].
Recent technical improvements involve the use of contrast
agents to facilitate identification of regional wall motion
abnormalities and to image myocardial perfusion. These
agents improve the interpretability of the images, but the
technique of perfusion imaging is not yet established.
Perfusion scintigraphy
SPECT perfusion is an established diagnostic test. It
provides a more sensitive and specific prediction of the
presence of CAD than exercise ECG [12]. The reported
sensitivity and specificity of exercise scintigraphy when
compared with invasive angiography range between 85 90%
and 70 75%, respectively [12].
Newer SPECT techniques with ECG gating improve
diagnostic accuracy in various patient populations, including
S9
women, diabetics, and elderly patients [23]. Adding
information from a simultaneously performed calcium score
using MDCT may further increase the accuracy [24].
Cardiovascular magnetic resonance imaging
Cardiac MRI stress testing with pharmacological stressors
can be used to detect wall motion abnormalities induced
by dobutamine infusion or perfusion abnormalities induced
by adenosine. Cardiac MRI has been applied only recently
in clinical practice and therefore fewer data have been
published compared with other established non-invasive
imaging techniques [12].
A recent meta-analysis showed that stress-induced wall
motion abnormalities from MRI had a sensitivity of 83%
and a specificity of 86% in patient-based analysis, and
perfusion imaging demonstrated 91% sensitivity and 81%
specificity [25]. When evaluated prospectively at multiple
sites, the diagnostic performance of stress perfusion MRI
shows similarly high sensitivity but lower specificity.
Multidetector computed tomography perfusion
MDCT can be used for perfusion imaging, but data obtained
in clinical settings are scarce.
Positron emission tomography
Studies with myocardial perfusion PET have reported
excellent diagnostic capabilities in the detection of CAD.
The comparisons of PET perfusion imaging have also favoured
PET over SPECT [26].
Meta-analysis of data obtained with PET demonstrated
92% sensitivity and 85% specificity for CAD detection,
superior to myocardial perfusion SPECT. Myocardial blood
flow in absolute units (mL/g/min) measured by PET further
improves diagnostic accuracy, especially in patients with
MVD, and can be used to monitor the effects of various
therapies.
5.3. Hybrid/combined imaging
The combination of anatomical and functional imaging
has become appealing because the spatial correlation
of structural and functional information of the fused
images may facilitate a comprehensive interpretation of
coronary lesions and their pathophysiological relevance.
This combination can be obtained either with image
coregistration or with devices that have two modalities
combined (MDCT and SPECT, MDCT and PET).
Single-centre studies evaluating the feasibility and
accuracy of combined imaging have demonstrated that
MDCT and perfusion imaging provide independent prognostic
information. No large or multicentre studies are currently
available.
5.4. Invasive tests
In common practice, many patients with intermediate
or high pretest CAD likelihood are catheterized without
prior functional testing. When non-invasive stress imaging
is contraindicated, non-diagnostic, or unavailable, the
measurement of FFR or coronary flow reserve is helpful.
Even experienced interventional cardiologists cannot predict
accurately the significance of most intermediate stenoses
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
on the basis of visual assessment or quantitative coronary
angiography [27,28]. Deferral of PCI [15,28] or CABG [27]
in patients with FFR >0.80 is safe and clinical outcome
is excellent. Thus, FFR is indicated for the assessment of
the functional consequences of moderate coronary stenoses
when functional information is lacking.
5.5. Prognostic value
Normal functional imaging results are linked with excellent
prognosis while documented ischaemia is associated with
increased risk for MACE. Prognostic information obtained
from MDCT imaging is becoming available.
5.6. Detection of myocardial viability
The prognosis of patients with chronic ischaemic systolic LV
dysfunction is poor, despite advances in various therapies.
Non-invasive assessment of myocardial viability should guide
patient management. Multiple imaging techniques including
PET, SPECT, and dobutamine stress echocardiography have
been extensively evaluated for assessment of viability
and prediction of clinical outcome after myocardial
revascularization. In general, nuclear imaging techniques
have a high sensitivity, whereas techniques evaluating
contractile reserve have somewhat lower sensitivity but
higher specificity. MRI has a high diagnostic accuracy to
assess transmural extent of myocardial scar tissue, but
its ability to detect viability and predict recovery of wall
motion is not superior to other imaging techniques [16].
The differences in performance of the various imaging
techniques are small, and experience and availability
commonly determine which technique is used. Current
evidence is mostly based on observational studies or metaanalyses, with the exception of two RCTs, both relating
to PET imaging [17]. Patients with a substantial amount
of dysfunctional but viable myocardium are likely to
benefit from myocardial revascularization and may show
improvements in regional and global contractile function,
symptoms, exercise capacity, and long-term prognosis [16].
6. Revascularization for stable coronary
artery disease
Depending on its symptomatic, functional, and anatomical
complexity, stable CAD can be treated by OMT only or
combined with revascularization using PCI or CABG. The
main indications for revascularization are persistence of
symptoms despite OMT and/or prognosis. Over the last
two decades significant advances in all three treatment
modalities have reduced many previous trials to historic
value.
6.1. Evidence basis for revascularization
The evidence basis for CABG and PCI is derived from RCTs
and large propensity-matched observational registries; both
have important strengths, but also limitations.
By eliminating bias, individual RCTs and their subsequent
meta-analyses [29 31] constitute the highest hierarchical
form of evidence-based medicine. However, their extrapolation to routine clinical practice is complicated by the fact
that their patient populations are often not representative
of those encountered in normal clinical practice (e.g. most
RCTs of PCI and CABG in ‘multivessel’ CAD enrolled <10%
of potentially eligible patients, most of whom actually had
single or double vessel CAD). Analysis on an intention-totreat basis is problematic when many patients cross over
from medical therapy to revascularization or from PCI to
CABG. Limited duration of follow-up (usually <5 years)
incompletely depicts the advantages of CABG, which initially
accrue with time but which may also eventually be eroded
by progressive vein graft failure.
In contrast, by capturing data on all interventions, large
observational registries may more accurately reflect routine
clinical practice. In the absence of randomization, however,
their fundamental limitation is that they cannot account for
all confounding factors, which may influence both the choice
and the outcome of different interventions. Propensity
matching for both cardiac and non-cardiac comorbidity
can only partially mitigate this problem. Accepting this
limitation, independent registries have consistently reported
that an initial strategy of CABG rather than PCI in propensitymatched patients with MVD or LM CAD improved survival over
a 3- to 5-year period by ~5%, accompanied by a four- to
seven-fold reduction in the need for reintervention [32 37].
The differing populations in RCTs and registries may partly
explain the apparent differences in the respective efficacies
of the two procedures, at least in patients with the most
severe CAD.
6.2. Impact of ischaemic burden on prognosis
The adverse impact of demonstrable ischaemia on clinical
outcome [death, myocardial infarction (MI), ACS, occurrence
of angina] has been well recognized for over two
decades [13,38]. While symptomatic patients with no or
little evidence of ischaemia have no prognostic benefit from
revascularization, asymptomatic patients with a significant
mass of ischaemic myocardium do [13,38]. Most recently,
in a small nuclear substudy of the COURAGE trial (which
reported no overall survival benefit of PCI over OMT),
involving just over 300 patients, 100 patients with >10%
ischaemic myocardium had a lower risk of death or MI with
revascularization [14].
6.3. Optimal medical therapy vs. percutaneous
coronary intervention
The efficacy of PCI (with or without stenting) vs. OMT
has been addressed in several meta-analyses [29,30,39 42]
and a large RCT [43]. Most meta-analyses reported no
mortality benefit, increased non-fatal periprocedural MI, and
reduced need for repeat revascularization with PCI. One
meta-analysis [41] reported a survival benefit for PCI over
OMT (respective mortalities of 7.4% vs. 8.7% at an average
follow-up of 51 months), but this study included patients
with recent MI and CABG patients in the revascularized
group. Another meta-analysis reported reduced mortality for
PCI vs. OMT, even after exclusion of MI patients [hazard ratio
(HR) 0.82, 95% confidence interval (CI) 0.68 0.99] [30].
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
The COURAGE RCT [43] randomized 2287 patients with
known significant CAD and objective evidence of myocardial
ischaemia to OMT alone or to OMT + PCI. At a median followup of 4.6 years, there was no significant difference in
the composite of death, MI, stroke, or hospitalization for
unstable angina. Freedom from angina was greater by 12%
in the PCI group at 1 year but was eroded by 5 years, by
which time 21% of the PCI group and 33% of the OMT group
had received additional revascularization (P < 0.001). The
authors concluded that an initial strategy of PCI in stable
CAD did not reduce the risk of death, MI, or MACE when
added to OMT. The severity of CAD in COURAGE was, at most,
moderate, with the relative proportions of one-, two- and
three-vessel CAD being 31%, 39%, and 30%, while only 31%
of patients had proximal LAD disease. Furthermore, patients
with LM disease were excluded and most patients had normal
LV function.
6.4. Percutaneous coronary intervention with
drug-eluting stents vs. bare metal stents
Brophy et al. [44], in an analysis of 29 trials involving
9918 patients, reported no difference between bare metal
stent (BMS) and balloon angioplasty in terms of death, MI,
or the need for CABG, but an ~5% absolute reduction in
restenosis with stenting. Subsequent meta-analyses [45] of
RCTs comparing DES with BMS reported similar rates of
death, cardiac death, and non-fatal MI, but a significant
reduction in the need for subsequent or repeat target
vessel revascularization (TVR) with DES. In contrast, Kirtane
et al. [46], in an unadjusted analysis of 182 901 patients in 34
observational studies of BMS and DES, reported a significant
reduction in mortality (HR 0.78, 95% CI 0.71 0.86) and MI
(HR 0.87, 95% CI 0.78 0.97) with DES. After multivariable adjustment, the benefits of DES were significantly attenuated
and the possibility that at least some of the clinical benefit of
DES might be due to concomitant dual antiplatelet therapy
(DAPT) could not be excluded. In a network meta-analysis
restricted to patients with non-acute CAD, sequential
advances in PCI techniques were not associated with
incremental mortality benefit in comparison with OMT [42].
6.5. Coronary artery bypass grafting vs.
medical therapy
The superiority of CABG to medical therapy in the management of specific subsets of CAD was firmly established
in a meta-analysis of seven RCTs [31], which is still the
major foundation for contemporary CABG. It demonstrated
a survival benefit of CABG in patients with LM or threevessel CAD, particularly when the proximal LAD coronary
artery was involved. Benefits were greater in those with
severe symptoms, early positive exercise tests, and impaired
LV function. The relevance of these findings to current
practice is increasingly challenged as medical therapy used
in the trials was substantially inferior to current OMT.
However, a recent meta-analysis reported a reduction in
the HR for death with CABG vs. OMT (HR 0.62, 95% CI
0.50 0.77) [30]. In addition, the benefits of CABG might
actually be underestimated because:
• most patients in the trials had a relatively low severity of
CAD;
S11
• analysis was conducted on an intention-to-treat basis
(even though 40% of the medical group crossed over to
CABG);
• only 10% of CABG patients received an internal thoracic
artery (ITA); however the most important prognostic
component of CABG is the use of one [47,48] or preferably
two [49] ITAs.
6.6. Percutaneous coronary intervention vs.
coronary artery bypass grafting
Isolated proximal left anterior descending artery
disease
There are two meta-analyses of >1900 [50] and >1200 [51]
patients, both of which reported no significant difference in
mortality, MI, or cerebrovascular accident (CVA), but a threefold increase in recurrent angina and a five-fold increase in
repeat TVR with PCI at up to 5 years of follow-up.
Multivessel disease (including SYNTAX trial)
There have been >15 RCTs of PCI vs. CABG in MVD [52] but
only one of OMT vs. PCI vs. CABG (MASS II) [53]. Most patients
in these RCTs actually had normal LV function with single
or double vessel CAD and without proximal LAD disease.
Meta-analyses of these RCTs reported that CABG resulted in
up to a five-fold reduction in the need for reintervention,
with either no or a modest survival benefit or a survival
benefit only in patients >65 years old (HR 0.82) and those
with diabetes (HR 0.7) [29]. The 5-year follow-up of the
MASS II [53] study of 611 patients (underpowered) reported
that the composite primary endpoint (total mortality,
Q-wave MI, or refractory angina requiring revascularization)
occurred in 36% of OMT, 33% of PCI and 21% of CABG patients
(P = 0.003), with respective subsequent revascularization
rates of 9%, 11% and 4% (P = 0.02).
The SYNTAX trial
In contrast to the highly selective patient populations
of previous RCTs, SYNTAX is a 5-year ‘all comers’ trial
of patients with the most severe CAD, including those
with LM and/or three-vessel CAD, who were entered into
either the trial or a parallel nested registry if ineligible
for randomization [4]. By having two components, SYNTAX
therefore captured real treatment decisions in a trial of
1800 patients randomized to PCI or CABG and in a registry of
1077 CABG patients (whose complexity of CAD was deemed
to be ineligible for PCI) and 198 PCI patients (considered
to be at excessive surgical risk). At 1 year, 12.4% of CABG
and 17.8% of PCI patients reached the respective primary
composite endpoint (P < 0.002) of death (3.5% vs. 4.4%;
P = 0.37), MI (3.3% vs. 4.8%; P = 0.11), CVA (2.2% vs. 0.6%;
P = 0.003), or repeat revascularization (5.9% vs. 13.5%;
P < 0.001) [4]. Unpublished data at 2 years showed major
adverse cardiac and cerebral event (MACCE) rates of
16.3% vs. 23.4% in favour of CABG (P < 0.001). Because PCI
failed to reach the pre-specified criteria for non-inferiority,
the authors concluded at both 1 [4] and 2 years that ‘CABG
remains the standard of care for patients with three-vessel
or LM CAD although the difference in the composite primary
endpoint was largely driven by repeat revascularization’.
Whether the excess of CVA in the CABG group in the
first year was purely periprocedural or also due to lower
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
use of secondary preventive medication (DAPT, statins,
antihypertensive agents, and ACE inhibitors) is not known.
Failure to reach criteria for non-inferiority therefore
means that all other findings are observational, sensitive to
the play of chance, and hypothesis generating. Nevertheless,
in 1095 patients with three-vessel CAD, the MACCE rates
were 14.4% vs. 23.8% in favour of CABG (P < 0.001). Only in
the tercile of patients with the lowest SYNTAX scores (<23)
was there no significant difference in MACCE between the
two groups. It is also noteworthy that the mortality and
repeat revascularization rates were similar in the 1077 CABG
registry patients, even though these patients had more
complex CAD.
Taking together all 1665 patients with three-vessel CAD
(1095 in the RCT and 570 in the registry), it appears that
CABG offers significantly better outcomes at 1 and 2 years
in patients with SYNTAX scores >22 (79% of all patients
with three-vessel CAD). These results are consistent with
previous registries [32 37] reporting a survival advantage
and a marked reduction in the need for repeat intervention
with CABG in comparison with PCI in patients with more
severe CAD.
Left main stenosis
CABG is still conventionally regarded as the standard of
care for significant LM disease in patients eligible for surgery,
and the CASS registry reported a median survival advantage
of 7 years in 912 patients treated with CABG rather than
medically [54]. While ESC guidelines on PCI state that ‘Stenting for unprotected LM disease should only be considered
in the absence of other revascularization options’ [55],
emerging evidence, discussed below, suggests that PCI
provides at least equivalent if not superior results to CABG
for lower severity LM lesions at least at 2 years of follow-up
and can justify some easing of PCI restrictions. However, the
importance of confirming that these results remain durable
with longer term follow-up (at least 5 years) is vital.
While LM stenosis is a potentially attractive target for
PCI because of its large diameter and proximal position in
the coronary circulation, two important pathophysiological
features may mitigate against the success of PCI: (i) up to
80% of LM disease involves the bifurcation known to be
at particularly high risk of restenosis; and (ii) up to 80%
of LM patients also have multivessel CAD where CABG, as
already discussed, may already offer a survival advantage.
The most ‘definitive’ current account of treatment of LM
disease by CABG or PCI is from the hypothesis-generating
subgroup analysis of the SYNTAX trial. In 705 randomized
LM patients, the 1-year rate of death (4.4% vs. 4.2%;
P = 0.88), CVA (2.7% vs. 0.3%; P = 0.009), MI (4.1% vs. 4.3%;
P = 0.97), repeat revascularization (6.7% vs. 12.0%; P = 0.02)
and MACCE (13.6% vs. 15.8%; P = 0.44) only favoured CABG
for repeat revascularization, but at a higher risk of CVA.
By SYNTAX score terciles, MACCE rates were 13.0% vs. 7.7%
(P = 0.19), 15.5% vs. 12.6% (P = 0.54), and 12.9% vs. 25.3%
(P = 0.08) for CABG vs. PCI in the lower (0 22), intermediate
(23 32), and high (33) terciles, respectively. Unpublished
data at 2 years show respective mortalities of 7.9% and 2.7%
(P = 0.02) and repeat revascularization rates of 11.4% and
14.3% (P = 0.44) in the two lower terciles, implying that PCI
may be superior to CABG at 2 years. Of note, among the
1212 patients with LM stenosis included in the registry or in
the RCTs, 65% had SYNTAX scores 33.
Support for the potential of PCI at least in lower risk
LM lesions comes from several other sources. In a metaanalysis of 10 studies, including two RCTs and the large
MAIN-COMPARE registry, of 3773 patients with LM stenosis,
Naik et al. [56] reported that there was no difference
between PCI and CABG in mortality or in the composite
endpoint of death, MI, and CVA up to 3 years, but up
to a four-fold increase in repeat revascularization with
PCI. These results were confirmed at 5 years in the MAINCOMPARE registry [57].
6.7. Recommendations
The two issues to be addressed are:
(i) the appropriateness of revascularization (Table 8);
(ii) the relative merits of CABG and PCI in differing patterns
of CAD (Table 9).
Current best evidence shows that revascularization can be
readily justified:
(i) on symptomatic grounds in patients with persistent
limiting symptoms (angina or angina equivalent) despite
OMT and/or
(ii) on prognostic grounds in certain anatomical patterns
of disease or a proven significant ischaemic territory
(even in asymptomatic patients). Significant LM stenosis,
and significant proximal LAD disease, especially in the
presence of multivessel CAD, are strong indications
for revascularization. In the most severe patterns of
CAD, CABG appears to offer a survival advantage as
well as a marked reduction in the need for repeat
revascularization, albeit at a higher risk of CVA,
especially in LM disease.
Table 8
Indications for revascularization in stable angina or silent ischaemia
Subset of CAD by anatomy
Left main >50% d
Any proximal LAD >50% d
2VD or 3VD with impaired
LV function d
Proven large area of
ischaemia (>10% LV)
Single remaining patent
vessel >50% stenosis d
1VD without proximal LAD
and without >10% ischaemia
For symptoms Any stenosis >50% with
limiting angina or angina
equivalent, unresponsive to
OMT
Dyspnoea/CHF and >10% LV
ischaemia/viability supplied
by >50% stenotic artery
No limiting symptoms with
OMT
For prognosis
a
Class a
Level b
Ref. c
I
I
I
A
A
B
[30,31,54]
[30 37]
[30 37]
I
B
[13,14,38]
I
C
III
A
[39,40,53]
I
A
[30,31,
39 43]
IIa
B
[14,38]
III
C
Class of recommendation.
Level of evidence.
c
References.
d
With documented ischaemia or FFR <0.80 for angiographic diameter stenoses
50 90%.
CAD = coronary artery disease; CHF = chronic heart failure; FFR = fractional
flow reserve; LAD = left anterior descending; LV = left ventricle; OMT = optimal
medical therapy; VD = vessel disease.
b
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 9
Indications for coronary artery bypass grafting vs. percutaneous coronary
intervention in stable patients with lesions suitable for both procedures
and low predicted surgical mortality
Ref. a
Subset of CAD by anatomy
Favours
CABG
Favours
PCI
1VD or 2VD non-proximal LAD
1VD or 2VD proximal LAD
3VD simple lesions, full functional
revascularization achievable with
PCI, SYNTAX score 22
3VD complex lesions, incomplete
revascularization achievable with
PCI, SYNTAX score >22
Left main (isolated or 1VD,
ostium/shaft)
Left main (isolated or 1VD, distal
bifurcation)
Left main + 2VD or 3VD,
SYNTAX score 32
Left main + 2VD or 3VD,
SYNTAX score 33
IIb C
IA
IA
IC
IIa B
IIa B
[30,31,50,51]
[4,30 37,53]
IA
III A
[4,30 37,53]
IA
IIa B
[4,54]
IA
IIb B
[4,54]
IA
IIb B
[4,54]
IA
III B
[4,54]
a
References.
CABG = coronary artery bypass grafting; CAD = coronary artery disease;
LAD = left anterior descending; PCI = percutaneous coronary intervention;
VD = vessel disease.
Recognizing that visual attempts to estimate the severity
of stenoses on angiography may either under- or overestimate the severity of lesions, the increasing use of
FFR measurements to identify functionally more important
lesions is a significant development (Section 5.4).
It is not feasible to provide specific recommendations
for the preferred method of revascularization for every
possible clinical scenario. Indeed it has been estimated
that there are >4000 possible clinical and anatomical permutations. Nevertheless, in comparing outcomes between
PCI and CABG, Tables 8 and 9 should form the basis of
recommendations by the Heart Team in informing patients
and guiding the approach to informed consent. However,
these recommendations must be interpreted according to
individual patient preferences and clinical characteristics.
For example, even if a patient has a typical prognostic
indication for CABG, this should be modified according to
individual clinical circumstances such as very advanced age
or significant concomitant comorbidity.
7. Revascularization in non-ST-segment
elevation acute coronary syndromes
NSTE-ACS is the most frequent manifestation of ACS and
represents the largest group of patients undergoing PCI.
Despite advances in medical and interventional treatments,
the mortality and morbidity remain high and equivalent to
that of patients with STEMI after the initial month. However,
patients with NSTE-ACS constitute a very heterogeneous
group of patients with a highly variable prognosis. Therefore,
early risk stratification is essential for selection of medical
as well as interventional treatment strategies. The ultimate
goals of coronary angiography and revascularization are
mainly two-fold: symptom relief, and improvement of
prognosis in the short and long term. Overall quality of
life, duration of hospital stay, and potential risks associated
S13
with invasive and pharmacological treatments should also be
considered when deciding on treatment strategy.
7.1. Intended early invasive or conservative
strategies
RCTs have shown that an early invasive strategy reduces
ischaemic endpoints mainly by reducing severe recurrent
ischaemia and the clinical need for rehospitalization and
revascularization. These trials have also shown a clear
reduction in mortality and MI in the medium term, while the
reduction in mortality in the long term has been moderate
and MI rates during the initial hospital stay have increased
(early hazard) [58]. The most recent meta-analysis confirms
that an early invasive strategy reduces cardiovascular death
and MI at up to 5 years of follow-up [59].
7.2. Risk stratification
Considering the large number of patients and the heterogeneity of NSTE-ACS, early risk stratification is important to
identify patients at high immediate and long-term risk of
death and cardiovascular events, in whom an early invasive
strategy with its adjunctive medical therapy may reduce
that risk. It is equally important, however, to identify
patients at low risk in whom potentially hazardous and costly
invasive and medical treatments provide little benefit or in
fact may cause harm.
Risk should be evaluated considering different clinical
characteristics, ECG changes, and biochemical markers.
Risk score models have therefore been developed. The
ESC Guidelines for NSTE-ACS recommend the GRACE
risk score (http://www.outcomes-umassmed.org/grace) as
the preferred classification to apply on admission and
at discharge in daily clinical practice [60]. The GRACE
risk score was originally constructed for prediction of
hospital mortality but has been extended for prediction
of long-term outcome across the spectrum of ACS and for
prediction of benefit with invasive procedures [61].
A substantial benefit with an early invasive strategy has
only been proved in patients at high risk. The recently
published meta-analysis [59] including the FRISC II [62],
the ICTUS [63], and the RITA III [64] trials showed
a direct relationship between risk, evaluated by a set
of risk indicators including age, diabetes, hypotension,
ST depression, and body mass index (BMI), and benefit from
an early invasive approach.
Troponin elevation and ST depression at baseline appear to
be among the most powerful individual predictors of benefit
from invasive treatment. The role of high sensitivity troponin
measurements has yet to be defined.
7.3. Timing of angiography and intervention
The issue of the timing of invasive investigation has been
a subject of discussion. A very early invasive strategy, as
opposed to a delayed invasive strategy, has been tested in
five prospective RCTs (Table 10).
A wealth of data supports a primary early invasive
strategy over a conservative strategy. There is no evidence
that any particular time of delay to intervention with
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 10
Randomized clinical trials comparing different invasive treatment strategies
Early invasive / conservative
Early / late invasive
Trials
FRISC
TRUCS
TIMI 18
VINO
RITA-3
ICTUS
ELISA
ISARCOOL
OPTIMA
TIMACS
ABOARD
Patients
Enrolment period
Time to angio (h) a
Mean age (year)
Women (%)
Diabetes (%)
Troponin ↑ at
inclusion (%)
Invasive (%) a,b
PCI/CABG (%) a,b
Primary outcome
2456
1996 98
96/408
66
30
12
55
148
1997 98
48/120
62
27
29
NA
2220
1997 99
22/79
62
34
28
54
131
1998 2000
6.2/1464
66
39
25
100
1810
1997 2002
48/1020
62
38
13
75
1199
2001 03
23/283
62
27
14
67
220
2000 01
6/50
63
30
14
68
410
2000 02
2.4/86
70
33
29
67
142
2004 07
0.5/25
62
32
20
46
3031
2003 08
14/50
65
35
27
77
352
2006 08
1.2/21
65
28
27
74
78/45
30/27
D/MI
6 months
+
100/61
43/16
D/MI/H
64/45
36/19
D/MI/A
6 months
+
73/39
50/27
D/MI
6 months
+
57/28
26/17
D/MI
12 months
+
79/54
51/10
D/MI/A
12 months
74/77
54/15
Infarct size
LDH
+
78/72
68/8
D/MI
1 month
+
100/99
99/0
D/MI/UR
30 days
74/69
57/28
D/MI/S
6 months
91/81
63/2
Troponin
release
Endpoint met
a
At the time the primary endpoint was reported.
Early invasive/conservative and early/late invasive, respectively.
A = hospital readmission; D = death; H = duration of hospitalization; MI = myocardial infarction; S = stroke; UR = unplanned revascularization.
b
Table 11
Indicators predicting high thrombotic risk or high-risk for progression to
myocardial infarction, which indicate emergent coronary angiography
Ongoing or recurrent ischaemia.
Dynamic spontaneous ST changes (>0.1 mV depression or transient
elevation).
Deep ST depression in anterior leads V2 V4 indicating ongoing posterior
transmural ischaemia.
Haemodynamic instability.
Major ventricular arrhythmia.
upstream pharmacological treatment, including intensive
antithrombotic agents, would be superior to providing
adequate medical treatment and performing angiography as
early as possible [65]. Ischaemic events as well as bleeding
complications tend to be lower and hospital stay can be
shortened with an early as opposed to a later invasive
strategy. In high-risk patients with a GRACE risk score
>140, urgent angiography should be performed within 24 h if
possible [66].
Patients at very high risk were excluded from all
RCTs so that life-saving therapy was not withheld.
Accordingly, patients with ongoing symptoms and marked
ST depression in anterior leads (particularly in combination
with troponin elevation) probably suffer from posterior
transmural ischaemia and should undergo emergency
coronary angiography (Table 11). Moreover, patients with a
high thrombotic risk or high risk of progression to MI should
be investigated with angiography without delay.
In lower risk subsets of NSTE-ACS patients, angiography
and subsequent revascularization can be delayed without
increased risk but should be performed during the same
hospital stay, preferably within 72 h of admission.
7.4. Coronary angiography, percutaneous
coronary intervention, and coronary
artery bypass grafting
An invasive strategy always starts with angiography. After
defining the anatomy and its associated risk features,
a decision about the type of intervention can be
made. The angiography in combination with ECG changes
often identifies the culprit lesion with irregular borders,
eccentricity, ulcerations, and filling defect suggestive of
intraluminal thrombi. For lesions with borderline clinical
significance and in patients with MVD, FFR measurement
provides important information for treatment decision
making [28]. Angiography should be performed urgently
for diagnostic purposes in patients at high risk and in
whom the differential diagnosis of other acute clinical
situations is unclear. Particularly in patients with ongoing
symptoms or marked troponin elevation, but in the absence
of diagnostic ECG changes, the identification of acute
thrombotic occlusion (primarily of the circumflex artery) is
important.
All trials that have evaluated early vs. late or invasive vs.
medical management have included PCI and CABG at the
discretion of the investigator. No prospective RCT has
specifically addressed the selection of mode of intervention
in patients with NSTE-ACS. In stabilized patients after an
episode of ACS, however, there is no reason to interpret
differently the results from RCTs comparing the two
revascularization methods in stable CAD. The mode of
revascularization should be based on the severity and
distribution of the CAD.
If PCI is desirable it should be recommended to identify
the culprit lesion with the help of angiographic determinants
and with ECG guidance, and to intervene on this lesion first.
In case of multiple angiographically significant non-culprit
stenoses or lesions whose severity is difficult to assess,
liberal use of FFR measurement is recommended in order to
decide on the treatment strategy [28]. Multivessel stenting
for suitable significant stenoses rather than stenting the
culprit lesion only has not been evaluated appropriately in a
randomized fashion. The optimal timing of revascularization
is different for PCI and for CABG. While the benefit from
PCI in patients with NSTE-ACS is related to its early
performance, the benefit from CABG is greatest when
patients can undergo surgery after several days of medical
stabilization.
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
7.5. Patient subgroups
Although subgroups of patients such as women and the
elderly may be at higher risk of bleeding, there are no
data supporting the suggestion that they should be treated
differently from other patients included in RCTs. A metaanalysis of eight RCTs showed that biomarker-positive
women derived a benefit from an early invasive strategy
comparable to that of men [67]. However, biomarkernegative women tended to have a higher event rate with
an early invasive procedure. Thus, early invasive procedures
should be avoided in low-risk, troponin-negative, female
patients.
Age is one of the most important risk indicators, yet
elderly patients experience a similar or greater benefit from
early invasive procedures [59]. Among the oldest patients,
one should prioritize relief of symptoms and avoidance of
bleeding complications.
Table 12 lists the recommendations for revascularization
in NSTE-ACS.
Table 12
Recommendations for revascularization in non-ST-segment elevation acute
coronary syndrome
a
b
c
Specification
Class a Level b Ref. c
An invasive strategy is indicated in patients with:
• GRACE score >140 or at least one high-risk
criterion.
• Recurrent symptoms.
• Inducible ischaemia at stress test.
An early invasive strategy (<24 h) is indicated in
patients with GRACE score >140 or multiple other
high-risk criteria.
A late invasive strategy (within 72 h) is indicated
in patients with GRACE score <140 or absence of
multiple other high-risk criteria but with recurrent
symptoms or stress-inducible ischaemia.
Patients at very high ischaemic risk (refractory
angina, with associated heart failure, arrhythmias
or haemodynamic instability) should be considered
for emergent coronary angiography (<2 h).
An invasive strategy should not be performed in
patients:
• At low overall risk.
• At a particular high-risk for invasive diagnosis or
intervention.
I
A
[64,
68 70]
I
A
I
A
[63,
64,66,
70 72]
[59,66,
68]
IIa
C
III
A
[59,68]
Class of recommendation.
Level of evidence.
References.
8. Revascularization in ST-segment
elevation myocardial infarction
8.1. Reperfusion strategies
8.1.1. Primary percutaneous coronary intervention
Primary PCI is defined as percutaneous intervention in the
setting of STEMI without previous or concomitant fibrinolytic
treatment. RCTs and meta-analyses comparing primary PCI
with in-hospital fibrinolytic therapy in patients within 6 12 h
after symptom onset treated in high-volume, experienced
centres have shown more effective restoration of vessel
patency, less re-occlusion, improved residual LV function,
and better clinical outcome with primary PCI [73]. Cities
and countries switching from fibrinolysis to primary PCI have
observed a sharp decrease in mortality after STEMI [74,75].
S15
American College of Cardiology/American Heart Association (ACC/AHA) guidelines specify that primary PCI should
be performed by operators who perform >75 elective
procedures per year and at least 11 procedures for STEMI
in institutions with an annual volume of >400 elective and
>36 primary PCI procedures [76]. Such a policy decision is
justified by the strong inverse volume-outcome relationship
observed in high-risk and emergency PCI. Therefore,
tolerance of low-volume thresholds for PCI centres for the
purpose of providing primary PCI is not recommended.
It is essential to make every effort to minimize all
time delays, especially within the first 2 h after onset of
symptoms, by the implementation of a system of care
network. As illustrated in Figure 1, the preferred pathway
is immediate transportation of STEMI patients to a PCIcapable centre offering an uninterrupted primary PCI service
by a team of high-volume operators. Patients admitted
to hospitals without PCI facilities should be transferred
to a PCI-capable centre and no fibrinolytics should be
administered if the expected time delay between first
medical contact (FMC) and balloon inflation is <2 h. If the
expected delay is >2 h (or >90 min in patients <75 years old
with large anterior STEMI and recent onset of symptoms),
patients admitted to a non-PCI centre should immediately
receive fibrinolysis and then be transferred to a PCI-capable
centre where angiography and PCI should be performed in a
time window of 3 24 h [77 80].
8.1.2. Fibrinolysis
Despite its frequent contraindications, limited effectiveness in inducing reperfusion, and greater bleeding risk,
fibrinolytic therapy, preferably administered as a prehospital treatment [81], remains an important alternative to
mechanical revascularization. In Europe, 5 85% of patients
with STEMI undergo primary PCI, a wide range that reflects
the variability or allocation of local resources and capabilities [82]. Even with an optimal network organization,
transfer delays may be unacceptably long before primary PCI
is performed, especially in patients living in mountain or rural areas or presenting to non-PCI centres. The incremental
benefit of primary PCI, over timely fibrinolysis, is jeopardized
when PCI-related delay exceeds 60 120 min, depending on
age, duration of symptoms, and infarct location [83,84].
Facilitated PCI, or pharmaco-mechanical reperfusion, is
defined as elective use of reduced or normal-dose fibrinolysis
combined with glycoprotein IIb IIIa (GPIIb IIIa) inhibitors
or other antiplatelet agents. In patients undergoing PCI
90 120 min after FMC, facilitated PCI has shown no
significant advantages over primary PCI. The use of
tenecteplase and aspirin as facilitating therapy was shown to
be detrimental compared with primary PCI, with increased
ischaemic and bleeding events, and a trend towards excess
mortality [85]. The combination of half-dose lytics with
GPIIb IIIa inhibitors showed a non-significant reduction in
adverse events at the price of excess bleeding [86].
Pre-hospital full-dose fibrinolysis has been tested in the
CAPTIM trial [81], using an emergency medical service (EMS)
able to perform pre-hospital diagnosis and fibrinolysis, with
equivalent outcome to primary PCI at 30 days and 5 years.
Following pre-hospital fibrinolysis, the ambulance should
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Symptoms of STEMI
EMS
Self-referral
GP/cardiologist
Pre-hospital
diagnosis & care
Private transportation
Ambulance
to Cath
Non-primary PCI
-capable centre
Primary PCI
-capable centre
PCI possible in <2 h
Immediate transfer to Cath Lab
YES
Primary PCI
NO
Rescue PCI
NO
Successful
fibrinolysis?
Transfer to ICU
of PCI-capable centre
Immediate
fibrinolysis
YES
Coronary angiography
3 – 24 h after FMC
Delayed PCI as required
EMS = emergency medical service; FMC = first medical contact; GP = general physician;
ICU = intensive care unit; PCI = percutaneous coronary intervention;
STEMI = ST-segment elevation myocardial infarction.
Fig. 1. Organization of ST-segment elevation myocardial infarction patient pathway describing pre- and in-hospital management and reperfusion strategies within
12 h of first medical contact.
transport the patient to a 24 h a day/7 days a week PCI
facility.
ischaemia and proven viability in a large myocardial territory
are candidates for mechanical revascularization.
8.1.3. Delayed percutaneous coronary intervention
In cases of persistent ST-segment elevation after fibrinolysis,
defined as more than half of the maximal initial elevation in
the worst ECG lead, and/or persistent ischaemic chest pain,
rapid transfer to a PCI centre for rescue angioplasty should
be considered [80,87]. Re-administration of a second dose
of fibrinolysis was not shown to be beneficial.
In the case of successful fibrinolysis, patients are
referred within 24 h for angiography and revascularization
as required [77 79].
Patients presenting between 12 and 24 h and possibly up to
60 h from symptom onset, even if pain free and with stable
haemodynamics, may still benefit from early coronary angiography and possibly PCI [88,89]. Patients without ongoing
chest pain or inducible ischaemia, presenting between 3 and
28 days with persistent coronary artery occlusion, did not
benefit from PCI [90,91]. Thus, in patients presenting days
after the acute event with a fully developed Q-wave MI, only
patients with recurrent angina and/or documented residual
8.1.4. Coronary artery bypass grafting
Emergent coronary artery bypass grafting
In cases of unfavourable anatomy for PCI or PCI failure,
emergency CABG in evolving STEMI should only be considered
when a very large myocardial area is in jeopardy and
surgical revascularization can be completed before this area
becomes necrotic (i.e. in the initial 3 4 h).
Urgent coronary artery bypass grafting
Current evidence points to an inverse relationship
between surgical mortality and time elapsed since STEMI.
When possible, in the absence of persistent pain or
haemodynamic deterioration, a waiting period of 3 7 days
appears to be the best compromise [92]. Patients with
MVD receiving primary PCI or urgent post-fibrinolysis PCI on
the culprit artery will need risk stratification and further
mechanical revascularization with PCI or surgery. Older age,
impaired LV function, and comorbidity are associated with a
higher surgical risk.
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
8.2. Cardiogenic shock and mechanical
complications
8.2.1. Cardiogenic shock
Cardiogenic shock is the leading cause of in-hospital
death for MI patients. Optimal treatment demands early
reperfusion as well as haemodynamic support to prevent
end-organ failure and death. Definitions of cardiogenic
shock, the diagnostic procedures as well as the medical,
interventional, and surgical treatment are discussed in
previous ESC Guidelines [93,94]. No time limit should be
set between onset of symptoms and invasive diagnosis
and revascularization in patients with cardiogenic shock,
whether or not they previously received fibrinolytic
treatment. In these patients, complete revascularization
has been recommended, with PCI performed in all critically
stenosed large epicardial coronary arteries [95].
8.2.2. Mechanical complications
Echocardiography should always be performed in acute
heart failure (AHF) to assess LV function and to rule out
life-threatening mechanical complications that may require
surgery such as acute mitral regurgitation (MR) secondary
to papillary muscle rupture, ventricular septal defect (VSD),
free wall rupture, or cardiac tamponade. The natural history
of these conditions is characterized by a rapid downhill
course and medical treatment alone results in close to 100%
mortality.
Free wall rupture requires prompt recognition and immediate pericardial drainage at the bedside. The incidence
of post-MI VSD is 0.2%. With persistent haemodynamic
deterioration despite the presence of an intra-aortic balloon
pump (IABP), surgery should be performed as soon as
possible [92]. Other than feasibility, there is limited
evidence to support percutaneous attempts at defect
closure either transiently using balloons or durably with
implantation of closure devices. Acute MR due to papillary
muscle rupture usually results in acute pulmonary oedema
and should be treated by immediate surgery.
Whenever possible, pre-operative coronary angiography
is recommended. Achieving complete revascularization in
addition to correcting the mechanical defect improves the
clinical outcome.
8.2.3. Circulatory assistance
The use of an IABP is recommended only in the presence
of haemodynamic impairment [96,97]. The IABP should be
inserted before angiography in patients with haemodynamic
instability (particularly those in cardiogenic shock and with
mechanical complications) [92]. The benefits of an IABP
should be balanced against device-related complications,
mostly vascular and more frequently observed in small
stature patients and/or females, patients with peripheral
arterial disease (PAD), and diabetics. An IABP should not
be used in patients with aortic insufficiency or aortic
dissection.
Mechanical circulatory assistance other than an IABP
can be offered at tertiary centres with an institutional
programme for mechanical assist therapy if the patient
continues to deteriorate and cardiac function cannot
maintain adequate circulation to prevent end-organ failure
(Figure 2). Extracorporeal membrane oxygenator (ECMO)
implantation should be considered for temporary support
in patients with AHF with potential for functional
recovery following revascularization [98]. If the heart
does not recover, the patient should undergo a thorough
neurological assessment (especially in the setting of a
pre-admittance out-of-hospital resuscitation or prolonged
periods with low cardiac output). The patient may be
considered for a surgical left ventricular assist device
(LVAD) or biventricular assist device (BiVAD) therapy
in the absence of permanent neurological deficits. In
young patients with no contraindication for transplant,
LVAD/BiVAD therapy as a bridge to transplant may be
indicated [99]. In some patients, total implantable assist
devices may be applied as a destination (or permanent)
therapy.
Several mechanical assist devices that can be implanted
percutaneously have been tested with disappointing results.
The use of percutaneous centrifugal pumps (Tandem
Heart) has not resulted in improved outcome after
STEMI [97]. Despite early haemodynamic recovery, secondary
complications have resulted in similar 30-day mortality
rates. The use of a microaxial propeller pump (Impella)
resulted in better haemodynamics but similar mortality after
30 days [100]. A meta-analysis summarizing the data from
three RCTs (100 patients) showed no difference in 30-day
mortality and a trend for more adverse events, such as
bleeding and vascular complications in the group receiving
percutaneous assist devices [101].
Table 13 lists the recommendations for reperfusion strategies in STEMI patients, Table 14 lists the recommendations
for PCI in STEMI, and Table 15 lists the recommendations
for the treatment of patients with AHF in the setting of
acute MI (AMI).
Table 13
Recommendations for reperfusion strategies in ST-segment elevation
myocardial infarction patients
Class a Level b Ref. c
Implementation of a well-functioning network
based on pre-hospital diagnosis, and fast
transport to the closest available primary
PCI-capable centre is recommended.
Primary PCI-capable centres should deliver
24 h per day/7 days per week on-call service,
be able to start primary PCI as soon as
possible and within 60 min from the initial
call.
In case of fibrinolysis, pre-hospital initiation
by properly equipped EMS should be
considered and full dose administered.
With the exception of cardiogenic shock, PCI
(whether primary, rescue, or post-fibrinolysis)
should be limited to the culprit stenosis
In PCI-capable centres, unnecessary
intermediate admissions to the emergency
room or the intensive care unit should be
avoided.
The systematic use of balloon
counterpulsation, in the absence of
haemodynamic impairment, is not
recommended.
a
I
A
[74,75]
I
B
[76,82,
102 105]
IIa
A
[81]
IIa
B
[96,106,
107]
III
A
[94,108,
109]
III
B
[96,97]
Class of recommendation.
Level of evidence.
References.
EMS = emergency medical service; PCI = percutaneous coronary intervention.
b
c
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Medical therapy
Inotropic support
Ventilatory support
IABP
Reperfusion
Revascularization
Patient stable
Patient unstable
ECMO support
Weaning
Cardiac function
recovers
No recovery
of cardiac
function
Cardiac function
recovers
Weaning
Assess neurological /
end organ function
Standard therapy
Irreversible neurological
deficit
Weaning
Normal neurological
function
Consider LVAD/BiVAD therapy
(BTT/DT)
BiVAD = biventricular assist device; BTT = bridge to transplantation; DT = destination therapy; ECMO = extracorporeal membrane oxygenator;
IABP = intra-aortic balloon pump; LVAD = left ventricular assist device
Fig. 2. Treatment algorithms for acute heart failure and cardiogenic shock. After failure of initial therapy including reperfusion and revascularization to stabilize
haemodynamics, temporary mechanical support using an extracorporeal membrane oxygenator should be considered. If weaning from the extracorporeal
membrane oxygenator fails or heart failure persists, left ventricular assist device/biventricular assist device therapy may be considered if neurological function
is not permanently impaired.
Table 14
Recommendations for percutaneous coronary intervention in ST-segment elevation myocardial infarction
Indication
Primary PCI
Is recommended in patients with chest pain/discomfort <12 h + persistent ST-segment elevation or
previously undocumented left bundle branch block.
Should be considered in patients with ongoing chest pain/discomfort >12 h + persistent ST-segment
elevation or previously undocumented left bundle branch block.
May be considered in patients with history of chest pain/discomfort >12 h and <24 h + persistent
ST-segment elevation or previously undocumented left bundle branch block.
PCI after fibrinolysis
Routine urgent PCI is indicated after successful fibrinolysis (resolved chest pain/discomfort and
ST-segment elevation).
Rescue PCI should be considered in patients with failed fibrinolysis.
Elective PCI/CABG
Is indicated after documentation of angina/positive provocative tests.
Not recommended in patients with fully developed Q wave MI and no further symptoms/signs of
ischaemia or evidence of viability in the infarct related territory.
a
Time from FMC
Class a
Level b
Ref. c
As soon as possible
and at any rate
<2 h from FMC d
As soon as possible
I
A
[83,84,94]
IIa
C
As soon as possible
IIb
B
[88,89]
Within 24 h e
I
A
[77 79]
As soon as possible
IIa
A
[80,87]
Evaluation prior to
hospital discharge
Patient referred >24 h
I
B
[36,41 43]
III
B
[90,91]
Class of recommendation.
Level of evidence.
References.
d
<90 min if patient presents <2 h from symptoms onset and has large infarct and low bleeding risk.
e
In order to reduce delay for patients with no reperfusion, transfer to PCI centre of all post-fibrinolysis patients is recommended.
CABG = coronary artery bypass grafting; FMC = first medical contact; MI = myocardial infarction; PCI = percutaneous coronary intervention.
b
c
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 15
Recommendations for treatment of patients with acute heart failure in the
setting of acute myocardial infarction
Patients with NSTE-ACS or STEMI
and unstable haemodynamics should
immediately be transferred for
invasive evaluation and target vessel
revascularization.
Immediate reperfusion is indicated in AHF
with ongoing ischaemia.
Echocardiography should be performed to
assess LV function and exclude mechanical
complications.
Emergency angiography and
revascularization of all critically narrowed
arteries by PCI/CABG as appropriate is
indicated in patients in cardiogenic shock.
IABP insertion is recommended in patients
with haemodynamic instability (particularly
those in cardiogenic shock and with
mechanical complications).
Surgery for mechanical complications of AMI
should be performed as soon as possible
with persistent haemodynamic deterioration
despite IABP.
Emergent surgery after failure of PCI or
of fibrinolysis is only indicated in patients
with persistent haemodynamic instability
or life-threatening ventricular arrhythmia
due to extensive ischaemia (LM or severe
3-vessel disease).
If the patient continues to deteriorate
without adequate cardiac output to prevent
end-organ failure, temporary mechanical
assistance (surgical implantation of
LVAD/BiVAD) should be considered.
Routine use of percutaneous centrifugal
pumps is not recommended.
Class a
Level b
Ref. c
I
A
[60,73,93,
94]
I
B
[60,93,94]
I
C
I
B
I
C
I
B
I
C
[95]
[92]
IIa
C
[98,99]
III
B
[97,100,
101]
a
Class of recommendation.
Level of evidence.
c
References.
AHF = acute heart failure; AMI = acute myocardial infarction; BiVAD =
bi-ventricular assist device; CABG = coronary artery bypass grafting;
IABP = intra-aortic balloon pump; LM = left main; LV = left ventricle; LVAD = left
ventricular assist device; NSTE-ACS = non-ST-segment elevation acute coronary
syndrome; PCI = percutaneous coronary intervention; STEMI = ST-segment
elevation myocardial infarction.
b
9. Special conditions
9.1. Diabetes
Diabetic patients represent an increasing proportion of CAD
patients, many of whom are treated with revascularization
procedures [110]. They are at increased risk, including longterm mortality, compared with non-diabetic patients [29],
whatever the mode of therapy used, and they may pose
specific problems, such as higher restenosis and occlusion
rates after PCI and CABG.
9.1.1. Indications for myocardial revascularization
The BARI 2D trial specifically addressed the question of
myocardial revascularization in diabetic patients with mostly
stable CAD [111]. The Heart Team reviewed the coronary
angiograms and judged whether the most appropriate
revascularization technique would be PCI or CABG. The
patients were then randomized to either OMT only, or
revascularization in addition to OMT. Of note, 4623 patients
S19
were screened for participation in the trial, of which ~50%
were included. Overall there was no difference after 5 years
in the rates of death, MI, or stroke between OMT (12.2%)
and revascularization (11.7%). In the PCI stratum, there was
no outcome difference between PCI and OMT. In the surgical
stratum, survival free of MACCE was significantly higher with
CABG (77.6%) than with medical treatment only (69.5%,
P = 0.01); survival, however, was not significantly different
(86.4% vs. 83.6%, P = 0.33).
In NSTE-ACS patients, there is no interaction between
the effect of myocardial revascularization and diabetic
status [62,63,69]. In both the FRISC-2 and TACTICS-TIMI 18
trials [62,69], an early invasive strategy was associated with
improved outcomes; in TACTICS-TIMI 18 [69], the magnitude
of the benefit in diabetic patients was greater than in nondiabetics.
In STEMI patients, the PCAT-2 [112] collaborative analysis
of 19 RCTs showed a similar benefit of primary PCI over
fibrinolytic treatment in diabetic and non-diabetic patients.
The odds ratio (OR) for mortality with primary PCI was 0.49
for diabetic patients (95% CI 0.31 0.79). Late PCI in patients
with a completely occluded coronary artery after STEMI past
the acute stage offered no benefit over medical therapy
alone, both in diabetic and non-diabetic patients [90].
9.1.2. Type of intervention: coronary artery bypass
grafting vs. percutaneous coronary intervention
All RCTs have shown higher rates of repeat revascularization
procedures after PCI, compared with CABG, in diabetic
patients [29]. A recent meta-analysis on individual data
from 10 RCTs of elective myocardial revascularization [29]
confirms a distinct survival advantage for CABG over PCI
in diabetic patients. Five-year mortality was 20% with
PCI, compared with 12.3% with CABG (OR 0.70, 95% CI
0.56 0.87), whereas no difference was found for nondiabetic patients; the interaction between diabetic status
and type of revascularization was significant. The AWESOME
trial [113] randomized high-risk patients (one-third with
diabetes) to PCI or CABG. At 3 years, there was no significant
difference in mortality between PCI-treated and CABGtreated diabetic patients. Finally, in diabetic patients from
the SYNTAX trial [4], the MACCE rate at 1 year was twice as
high with PCI using paclitaxel-eluting stent (PES), compared
with CABG, a difference driven by repeat revascularization.
Though admittedly underpowered, the CARDia trial [114]
is the only trial reported to date that was specifically
designed to compare PCI using BMS (31%) or DES (69%)
with CABG in diabetic patients. At 1 year, the combined
incidence of death, MI, or stroke was 10.5% in the CABG
arm and 13.0% in the PCI arm (HR 1.25, 95% CI 0.75 2.09).
Repeat revascularization was 2.0% vs. 11.8%, respectively
(P < 0.001).
Besides RCTs, registry data, such as the New York
registry [34], show a trend to improved outcomes in diabetic
patients treated with CABG compared with DES (OR for
death or MI at 18 months 0.84, 95% CI 0.69 1.01).
9.1.3. Specific aspects of percutaneous coronary
intervention
A large collaborative network meta-analysis has compared
DES with BMS in 3852 diabetic patients [115]. Mortality
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
appeared significantly (P = 0.02) higher with DES compared
with BMS when the duration of DAPT was <6 months (eight
trials); in contrast, no difference in mortality and the
combined endpoint death or MI was found when DAPT
duration was 6 months (27 trials). Whatever the duration of
DAPT, the need for repeat TVR was considerably less with DES
than BMS [OR 0.29 for sirolimus-eluting stent (SES); 0.38 for
PES], similar to the restenosis reduction observed in nondiabetic patients. There are no robust data to support the
use of one DES over another in patients with diabetes.
9.1.4. Type of coronary artery bypass grafting
intervention
Diabetic patients usually have extensive CAD and require
multiple grafts. There is no direct randomized evidence
regarding the use of only one vs. two ITA conduits in diabetic
patients. Currently, only observational evidence suggests
that using both arterial conduits improves outcomes, without
compromising sternal stability [49]. A non-randomized comparison of bilateral ITA surgery with PCI in diabetic patients
showed improved outcomes with the use of bilateral arterial
grafts, though 5-year survival was not significantly different
from that of PCI-treated patients [116]. Although diabetes
is a risk factor for wound infection and mediastinitis, the
impact of the use of bilateral ITA on these complications is
debated.
has not been confirmed with the use of newer pancreaticspecific sulfonylureas.
Glitazones
Thiazolidinediones may be associated with lower restenosis rates after PCI with BMS; however, they are associated
with an increased risk of heart failure.
Insulin
No trial has shown improved PCI outcome after STEMI with
the administration of insulin or glucose insulin potassium
(GIK) [117 119]. After CABG, the incidence of secondary
endpoints, such as atrial fibrillation (AF), myocardial injury,
wound infection, or hospital stay, was reduced after GIK
infusion [120,121]. However, the NICE-SUGAR trial [122]
assessed the impact of insulin therapy with tight blood
glucose control in patients admitted to the intensive care
unit for various clinical and surgical conditions. An increase
in severe hypoglycaemic episodes was noted in the tighter
blood glucose control arm of the trial, and 90-day mortality
was increased.
Table 16 shows specific recommendations for revascularization in diabetic patients.
Table 16
Specific recommendations for diabetic patients
In patients presenting with STEMI,
primary PCI is preferred over fibrinolysis if
it can be performed within recommended
time limits.
In stable patients with extensive CAD,
revascularization is indicated in order to
improve MACCE-free survival.
Use of DES is recommended in order to
reduce restenosis and repeat TVR.
In patients on metformin, renal function
should be carefully monitored after
coronary angiography/PCI.
CABG should be considered, rather than
PCI, when the extent of the CAD justifies a
surgical approach (especially MVD), and the
patient’s risk profile is acceptable.
In patients with known renal failure
undergoing PCI, metformin may be stopped
48 h before the procedure.
Systematic use of GIK in diabetic patients
undergoing revascularization is not
indicated.
9.1.5. Antithrombotic pharmacotherapy
There is no indication that antithrombotic pharmacotherapy
should differ between diabetic vs. non-diabetic patients
undergoing elective revascularization. In ACS trials, there is
no indication that the antithrombotic regimen should differ
between diabetic and non-diabetic patients [65,85,86].
Although an interaction between diabetic status and efficacy
of GPIIb IIIa inhibitors was noted in earlier trials without
concomitant use of thienopyridines, this was not confirmed
in the more recent Early-ACS trial [65]. In the current
context of the use of high-dose oral antiplatelet agents,
diabetic patients do not benefit from the routine addition
of GPIIb IIIa inhibitors.
9.1.6. Antidiabetic medications
There have been only a few specific trials of antidiabetic
medications in patients undergoing myocardial revascularization.
Class a
Level b
Ref. c
I
A
[112]
I
A
[111]
I
A
[115]
I
C
IIa
B
IIb
C
III
B
[29,34,
113,116]
[117,118,
122]
a
Metformin
Because of the risk of lactic acidosis in patients receiving
iodinated contrast media, it is generally stated that
metformin should be interrupted before angiography or PCI,
and reintroduced 48 h later, only after assessment of renal
function. However, there is no convincing evidence for such a
recommendation. Checking renal function after angiography
in patients on metformin and stopping metformin when renal
function deteriorates might be an acceptable alternative
to suspension of metformin in all patients. In patients
with renal failure, metformin should preferably be stopped
before the procedure.
Sulfonylureas
Observational data have reported concern about the use
of sulfonylureas in patients treated with primary PCI. This
Class of recommendation.
Level of evidence.
References.
CABG = coronary artery bypass grafting; CAD = coronary artery disease;
DES = drug-eluting stent; GIK = glucose insulin potassium; MACCE = major
adverse cardiac and cerebral event; MVD = multivessel disease; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial
infarction; TVR = target vessel revascularization.
b
c
9.2. Myocardial revascularization in patients
with chronic kidney disease
Cardiovascular disease is the main cause of mortality in patients with severe chronic kidney disease (CKD), particularly
in combination with diabetes. Cardiovascular mortality is
much higher among patients with CKD than in the general
population, and CAD is the main cause of death among
diabetic patients after kidney transplantation. Myocardial
S21
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
revascularization procedures may therefore significantly
improve survival of patients with CKD. However, the use of
contrast media during diagnostic and interventional vascular
procedures represents the most common cause of acute
kidney injury in hospitalized patients. The detection of a
minimum serum creatinine rise (5 10% from baseline), 12 h
after angiography or PCI, may be a very simple and early
indicator of contrast-induced nephropathy (CIN). CABG can
also cause acute kidney injury or worsen CIN.
Definition of chronic kidney disease
Estimation of glomerular renal function in patients
undergoing revascularization requires calculation of the
glomerular filtration rate (GFR) and cannot be based on
serum creatinine levels. Normal GFR values are ~100
130 mL/min/1.73 m2 in young men, and 90 120 mL/min/
1.73 m2 in young women, depending on age, sex, and body
size. CKD is classified into five different stages according to
the progressive GFR reduction and evidence of renal damage. The cut-off GFR value of 60 mL/min/1.73 m2 correlates
significantly with MACE. In diabetic patients, the diagnosis
of proteinuria, independently of GFR values, supports the
diagnosis of CKD with similar prognostic implications due
to diabetic macroangiopathy. Cystatin-c is an alternative
marker of renal function and may be more reliable than
serum creatinine in elderly patients (>75 years old).
Patients with mild or moderate chronic kidney
disease
For patients with mild (60 GFR < 90 mL/min/1.73 m2 )
or moderate (30 GFR < 60 mL/min/1.73 m2 ) CKD, there is
consistent evidence supporting CABG as a better treatment
than PCI, particularly when diabetes is the cause of the
CKD. An off-pump approach may be considered when surgical
revascularization is needed. When there is an indication
for PCI, there is only weak evidence suggesting that DES
are superior to BMS in terms of reduced recurrence of
ischaemia. The potential benefit of DES should be weighed
against the risk of side effects that derive from the need for
prolonged DAPT, increased risk of late thrombosis, increased
restenosis propensity of complex calcified lesions, and a
medical condition often requiring multiple diagnostic and
therapeutic procedures. Available data refer to the use of
SESs and PESs, with no robust evidence favouring either one
or any of the newer generation DES in this subset.
Patients with severe chronic kidney and end stage
renal disease or in haemodialysis
In the subset of patients with severe CKD (GFR
<30 mL/min/1.73 m2 ) and end stage renal disease (ESRD)
or those in haemodialysis, differences in favour of surgery
over PCI are less consistent. Surgery confers a better eventfree survival in the long term, but in-hospital mortality and
complication rates are higher, while the opposite is true
for PCI. Selection of the most appropriate revascularization
strategy must therefore account for the general condition of
the patient and his or her life expectancy, the least invasive
approach being more appropriate in the most fragile and
compromised patient. DES has not been proved superior to
BMS and should not be used indiscriminately. Indeed, it has
well been established that CKD is an independent predictor
of (very) late DES thrombosis with HR between 3.1 and 6.5.
Candidates for renal transplantation must be screened
for myocardial ischaemia and those with significant CAD
should not be denied the potential benefit of myocardial
revascularization. PCI using BMS should be considered if
subsequent renal transplantation is likely within 1 year.
Prevention of CIN
All patients with CKD undergoing diagnostic catheterization should receive preventive hydration with isotonic saline
to be started at least 12 h before angiography and continued
for at least 24 h afterwards, in order to reduce the risk of CIN
(Table 17). OMT before exposure to contrast media should
Table 17
Recommendations for prevention of contrast-induced nephropathy
Intervention
Dose
All patients with CKD
OMT (including statins, b-blockers, and ACE inhibitors or According to clinical indications.
sartans) is recommended.
Hydration with isotonic saline is recommended.
1 mL/kg/h 12 h before and continued for 24 h after the procedure
(0.5 mL/kg/h if EF <35% or NYHA >2).
N-Acetylcysteine administration may be considered.
600 1200 mg 24 h before and continued for 24 h after the procedure.
Infusion of sodium bicarbonate 0.84% may be
1 h before: bolus = body weight in kg × 0.462 mEq
considered.
i.v. infusion for 6 h after the procedure = body weight in kg ×
0.154 mEq per hour.
Patients with mild, moderate, or severe CKD
Use of LOCM or IOCM is recommended.
<350 mL or <4 mL/kg
Patients with severe CKD
Prophylactic haemofiltration 6 h before complex PCI
should be considered.
Elective haemodialysis is not recommended as a
preventive measure.
a
Fluid replacement rate 1000 mL/h without weight loss and saline
hydration, continued for 24 h after the procedure.
Class a
Level b
Ref. c
I
A
[123]
I
A
IIb
IIb
A
A
[127
130]
[128,129]
[127,128,
130]
Id
Ad
[124,
131 133]
IIa
B
[134,135]
III
B
[136]
Class of recommendation.
Level of evidence.
c
References.
d
Recommendation pertains to the type of contrast.
ACE = angiotensin-converting enzyme; CKD = chronic kidney disease; EF = ejection fraction; IOCM = iso-osmolar contrast media; i.v. = intravenous; LOCM = low
osmolar contrast media; NYHA = New York Heart Association; OMT = optimal medical therapy; PCI = percutaneous coronary intervention.
b
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
include statins, ACE inhibitors or sartans, and b-blockers as
recommended [123].
Although performing diagnostic and interventional procedures separately reduces the total volume exposure to
contrast media, the risk of renal atheroembolic disease
increases with multiple catheterizations. Therefore, in CKD
patients with diffuse atherosclerosis, a single invasive
approach (diagnostic angiography followed by ad hoc PCI)
may be considered, but only if the contrast volume can
be maintained below 4 mL/kg. The risk of CIN increases
significantly when the ratio of contrast volume to GFR
exceeds 3.7 [124].
For patients undergoing CABG, the effectiveness of the
implementation of pharmacological preventive measures
such as clonidine, fenoldopam, natriuretic peptides,
N-acetylcysteine [125] or elective pre-operative haemodialysis remain unproved [126].
Table 18 lists the specific recommendations for patients
with mild to moderate CKD.
Table 18
Specific recommendations for patients with mild to moderate chronic kidney
disease
Class a
CABG should be considered, rather than IIa
PCI, when the extent of the CAD justifies
a surgical approach, the patient’s risk
profile is acceptable, and life expectancy
is reasonable.
Off-pump CABG may be considered,
IIb
rather than on-pump CABG.
For PCI, DES may be considered, rather
IIb
than BMS.
Level b
Ref. c
B
[32,137 139]
B
[140]
C
a
Class of recommendation.
Level of evidence.
References.
BMS = bare metal stent; CABG = coronary artery bypass grafting;
CAD = coronary artery disease; DES = drug-eluting stent; PCI = percutaneous
coronary intervention.
b
c
Table 19
Recommendations for combined valve surgery and coronary artery bypass
grafting
Combined valve surgery and:
CABG is recommended in patients with a primary
indication for aortic/mitral valve surgery and coronary
artery diameter stenosis 70%.
CABG should be considered in patients with a primary
indication for aortic/mitral valve surgery and coronary
artery diameter stenosis 50 70%.
Combined CABG and:
Mitral valve surgery is indicated in patients with a
primary indication for CABG and severe c ischaemic
mitral regurgitation and EF >30%.
Mitral valve surgery should be considered in patients
with a primary indication for CABG and moderate
ischaemic mitral regurgitation provided valve repair is
feasible, and performed by experienced operators.
Aortic valve surgery should be considered in patients
with a primary indication for CABG and moderate
aortic stenosis (mean gradient 30 50 mmHg or Doppler
velocity 3 4 m/s or heavily calcified aortic valve even
when Doppler velocity 2.5 3 m/s).
Class a
Level b
I
C
IIa
C
I
C
IIa
C
IIa
C
a
Class of recommendation.
Level of evidence.
c
Definition of severe mitral regurgitation is available in the ESC
Guidelines on Valvular Heart Disease. Eur Heart J 2007;28:230 268 and
www.escardio.org/guidelines.
CABG = coronary artery bypass grafting; EF = ejection fraction.
b
replacement and CABG may represent too high a risk for a
single combined operation. Alternative treatments include
using ‘hybrid’ procedures, which involve a combination
of both scheduled surgery for valve replacement and
planned PCI for myocardial revascularization. At present,
however, the data on hybrid valve/PCI procedures are very
limited, being confined to case reports and small case
series [143]. Another option that may be considered in
these high-risk surgical patients is transcatheter aortic valve
implantation [144].
9.3. Myocardial revascularization in patients
requiring valve surgery
9.4. Associated carotid/peripheral arterial
disease
Coronary angiography is recommended in all patients with
valvular heart disease requiring valve surgery, apart from
young patients (men <40 years and pre-menopausal women)
with no risk factors for CAD, or when the risks of
angiography outweigh the benefits, e.g. in cases of aortic
dissection [141]. Overall, 40% of patients with valvular heart
disease will have concomitant CAD. The indications for
combining valve surgery with CABG in these patients are
summarized in Table 19. Of note, in those patients undergoing aortic valve replacement who also have significant CAD,
the combination of CABG and aortic valve surgery reduces
the rates of perioperative MI, perioperative mortality, late
mortality and morbidity when compared with patients
not undergoing simultaneous CABG [142]. This combined
operation, however, carries an increased risk of mortality
of 1.6 1.8% over isolated aortic valve replacement.
Overall the prevalence of valvular heart disease is rising as
the general population ages. Accordingly, the risk profile of
patients undergoing surgery is increasing. The consequence
of this change is that some patients requiring valve
9.4.1. Associated coronary and carotid artery disease
The incidence of significant carotid artery disease in patients
scheduled for CABG depends on age, cardiovascular risk
factors, and screening method. The aetiology of postCABG stroke is multifactorial and the main causes are
atherosclerosis of the ascending aorta, cerebrovascular
disease, and macroembolism of cardiac origin. Carotid
bifurcation stenosis is a marker of global atherosclerotic
burden that, together with age, cardiovascular risk factors,
previous stroke or transient ischaemic attack (TIA),
rhythm and coagulation disturbances, increases the risk of
neurological complications during CABG. Conversely, up to
40% of patients undergoing carotid endarterectomy (CEA)
have significant CAD and may benefit from pre-operative
cardiac risk assessment [123].
Risk factors for stroke associated with myocardial
revascularization
The incidence of perioperative stroke after on-pump
CABG varies from 1.5% to 5.2% in prospective studies
S23
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 20
Carotid artery screening before planned myocardial revascularization
Duplex ultrasound scanning is recommended in
patients with previous TIA/stroke or carotid bruit on
auscultation.
Duplex ultrasound scanning should be considered in
patients with LM disease, severe PAD, or 75 years.
MRI, CT, or digital subtraction angiography may be
considered if carotid artery stenosis by ultrasound
is >70% c and myocardial revascularization is
contemplated.
Class a
Level b
I
C
IIa
C
IIb
C
a
Class of recommendation.
Level of evidence.
c
Supplementary data associated with this article can be found, in the online
version, at doi:10.1016/j.ejcts.2010.08.019 and also at www.eacts.org.
CT = computed tomography; LM = left main; MRI = magnetic resonance
imaging; PAD = peripheral arterial disease; TIA = transient ischaemic attack.
stroke rate can be reliably documented to be <3% and life
expectancy is >5 years. In women with asymptomatic carotid
disease or patients with a life expectancy of <5 years,
the benefit of carotid revascularization is dubious [145].
In the absence of clear proof that staged or synchronous
CEA or carotid artery stenting (CAS) is beneficial in patients
undergoing CABG, all patients should be assessed on an
individual basis, by a multidisciplinary team including a
neurologist. This strategy is also valid for patients scheduled
for PCI. For carotid revascularization in CABG patients see
Table 21; for PCI patients see Table 22.
b
Table 21
Carotid revascularization in patients scheduled for coronary artery bypass
grafting
Class a
and from 0.8% to 3.2% in retrospective studies. The most
common single cause of post-CABG stroke is embolization of
atherothrombotic debris from the aortic arch, and patients
with carotid stenosis also have a higher prevalence of
aortic arch atherosclerosis. Although symptomatic carotid
artery stenosis is associated with an increased stroke
risk, 50% of strokes after CABG do not have significant
carotid artery disease and 60% of territorial infarctions
on computed tomography (CT) scan/autopsy cannot be
attributed to carotid disease alone. Furthermore, only 45%
of strokes after CABG are identified within the first day
after surgery while 55% of strokes occur after uneventful
recovery from anaesthesia and are attributed to AF, low
cardiac output, or hypercoagulopathy resulting from tissue
injury. Intraoperative risk factors for stroke are duration
of cardiopulmonary bypass (CPB), manipulation of the
ascending aorta, and arrhythmias. Off-pump CABG has been
shown to decrease the risk of stroke, especially when the
ascending aorta is diseased, and particularly if a no-touch
aorta technique is used.
In patients with carotid artery disease undergoing
PCI, although the risk of stroke is low (0.2%), ACS,
heart failure (HF), and widespread atherosclerosis are
independent risk factors. Recommendations for carotid
artery screening before myocardial revascularization are
listed in Table 20.
Carotid revascularization in patients scheduled for
coronary artery bypass grafting or percutaneous
coronary intervention
In patients with previous TIA or non-disabling stroke and a
carotid artery stenosis (50 99% in men and 70 99% in women)
the risk of stroke after CABG is high, and CEA by experienced
teams may reduce the risk of stroke or death [145] (see
figure in Appendix for methods of measuring carotid artery
stenosis). There is no guidance on whether the procedures
should be staged or synchronous. On the other hand, in
asymptomatic unilateral carotid artery stenosis, isolated
myocardial revascularization should be performed due to
the small risk reduction in stroke and death rate obtained
by carotid revascularization (1% per year) [145]. Carotid
revascularization may be considered in asymptomatic men
with bilateral severe carotid artery stenosis or contralateral
occlusion if the risk of post-procedural 30-day mortality or
Level b
Ref. c
CEA or CAS should be performed only by
I
A
[145]
teams with demonstrated 30-day combined
death-stroke rate:
<3% in patients without previous
neurological symptoms
<6% in patients with previous neurological
symptoms.
C
The indication for carotid revascularization I
should be individualized after discussion
by a multidisciplinary team including a
neurologist.
The timing of the procedures (synchronous
I
C
or staged) should be dictated by local
expertise and clinical presentation targeting
the most symptomatic territory first.
In patients with previous TIA/non-disabling stroke, carotid
revascularization:
Is recommended in 70 99% carotid stenosis. I
C
May be considered in 50 69% carotid
IIb
C
stenosis in men with symptoms <6 months.
Is not recommended if carotid stenosis
III
C
<50% in men and <70% in women.
In patients with no previous TIA/stroke, carotid revascularization:
May be considered in men with bilateral
IIb
C
70 99% carotid stenosis or 70 99% carotid
stenosis + contralateral occlusion.
Is not recommended in women or patients
III
C
with a life expectancy <5 years.
a
Class of recommendation.
Level of evidence.
References.
CAS = carotid artery stenting; CEA = carotid endarterectomy; TIA = transient
ischaemic attack.
b
c
Table 22
Carotid revascularization in patients scheduled for percutaneous coronary
intervention
The indication for carotid revascularization should be
individualized after discussion by a multidisciplinary
team including a neurologist.
CAS should not be combined with elective PCI during
the same endovascular procedure except in the
infrequent circumstance of concomitant acute severe
carotid and coronary syndromes.
a
Class a
Level b
I
C
III
C
Class of recommendation.
Level of evidence.
CAS = carotid artery stenting; PCI = percutaneous coronary intervention.
b
S24
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 23
Recommendations for the method of carotid revascularization
CEA remains the procedure of choice but
selection of CEA versus CAS depends on
multidisciplinary assessment.
Aspirin is recommended immediately before
and after carotid revascularization.
Patients who undergo CAS should receive
DAPT for at least 1 month after stenting.
CAS should be considered in patients with:
• post-radiation or post-surgical stenosis
• obesity, hostile neck, tracheostomy,
laryngeal palsy
• stenosis at different carotid levels or upper
internal carotid artery stenosis
• severe comorbidities contraindicating CEA.
CAS is not recommended in patients with:
• heavily calcified aortic arch or protruding
atheroma
• internal carotid artery lumen
diameter <3 mm
• contraindication to DAPT.
Class a
Level b
Ref. c
I
B
[147,
149]
I
A
[150,
151]
I
C
IIa
C
III
C
a
Class of recommendation.
Level of evidence.
c
References.
CAS = carotid artery stenting; CEA = carotid endarterectomy; DAPT = dual
antiplatelet therapy.
b
Choice of revascularization method in patients with
associated carotid and coronary artery disease
See Table 23. Few patients scheduled for CABG require
synchronous or staged carotid revascularization and, in this
case, CEA remains the procedure of choice. Indeed the
two most recent meta-analyses comparing CAS with CEA
documented that CAS results in a significant increase in
30-day death or stroke compared with CEA (OR 1.60, 95% CI
1.26 2.02) [146]. This was confirmed by the International
Carotid Stenting Study, which randomized 855 patients
to CAS and 858 patients to CEA and showed that the
incidence of stroke, death, or MI was 8.5% in the stenting
group vs. 5.2% in the endarterectomy group (HR 1.69;
P = 0.006) [147]. In an MRI substudy, new post-procedural
lesions occurred more frequently after CAS than after CEA
(OR 5.2; P < 0.0001) [148]. The recently published CREST
trial [149], which included 50% of asymptomatic patients,
showed that the 30-day risk of death, stroke, and MI was
similar after CAS (5.2%) or CEA (2.3%). Perioperative MI rates
were 2.3% after CEA and 1.1% after CAS (P = 0.03), while
perioperative stroke rates were 2.3 and 4.1%, respectively
(P = 0.01). Pooling these results with previous RCTs will help
determine which patient subgroups might benefit more from
CAS or CEA.
Both CEA and CAS should be performed only by
experienced teams, adhering to accepted protocols and
established indications. CAS is indicated when CEA has been
contraindicated by a multidisciplinary team due to severe
comorbidities or unfavourable anatomy. In patients with a
mean EuroSCORE of 8.6, good results with CAS performed
immediately before CABG (hybrid procedure) were reported
by experienced operators. This strategy should be reserved
for very high risk patients in need of urgent CABG and
previous neurological symptoms. In patients scheduled for
myocardial revascularization, without previous neurological
symptoms, who are poor surgical candidates owing to severe
comorbidities, there is no evidence that revascularization,
with either CEA or CAS, is superior to OMT. A systematic
review of staged CAS and CABG, in which 87% of the patients
were asymptomatic and 82% had unilateral lesions, showed
a high combined death and stroke rate at 30 days (9%).
This high procedural risk cannot be justified in neurologically
asymptomatic patients with unilateral carotid disease.
9.4.2. Associated coronary and peripheral arterial
disease
PAD is an important predictor of adverse outcome after
myocardial revascularization, and portends a poor longterm prognosis [152]. Patients with clinical evidence of PAD
are at significantly higher risk for procedural complications
after either PCI or CABG. When comparing the outcomes of
CABG vs. PCI in patients with PAD and MVD, CABG shows
a trend for improved survival. Risk-adjusted registry data
have shown that patients with MVD and PAD undergoing
CABG have better survival at 3 years than similar patients
undergoing PCI, in spite of higher in-hospital mortality.
However, with no solid data available in this population, the
two myocardial revascularization approaches are probably
as complementary in patients with PAD as they are in other
CAD patients.
Non-cardiac vascular surgery in patients with
associated coronary artery disease
Patients scheduled for non-cardiac vascular surgery are
at significant risk of cardiovascular morbidity and mortality
due to a high incidence of underlying symptomatic or
asymptomatic CAD. Pre-operative cardiac risk assessment in
vascular surgery patients has been addressed in previously
published ESC Guidelines [123]. Results of the largest
RCT demonstrated that there is no reduction in postoperative MI, early or long-term mortality among patients
randomized to prophylactic myocardial revascularization
compared with patients allocated to OMT before major
vascular surgery [153]. Included patients had preserved
left ventricular ejection fraction (LVEF) and stable CAD.
By contrast, the DECREASE-V pilot study [154] included
only high-risk patients [almost half had ejection fraction
(EF) <35% and 75% had three-vessel or LM disease],
with extensive stress-induced ischaemia evidenced by
dobutamine echocardiography or stress nuclear imaging.
This study confirmed that prophylactic myocardial revascularization did not improve outcome [154]. Selected
high-risk patients may still benefit from previous or
concomitant myocardial revascularization with options
varying from a one-stage surgical approach to combined
PCI and peripheral endovascular repair or hybrid procedures [155].
RCTs selecting high-risk patients, cohort studies, and
meta-analyses provide consistent evidence of a decrease
in cardiac mortality and MI due to b-blockers and
statins, in patients undergoing high-risk non-cardiac vascular
surgery [123] or endovascular procedures [152].
Table 24 summarizes the management of associated
coronary and PAD.
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 24
Management of patients with associated coronary and peripheral arterial
disease
In patients with unstable CAD, vascular surgery
is postponed and CAD treated first, except when
vascular surgery cannot be delayed due to a
life-threatening condition.
b-blockers and statins are indicated prior to and
continued post-operatively in patients with
known CAD who are scheduled for high-risk
vascular surgery.
The choice between CABG and PCI should be
individualized and assessed by a Heart Team
considering patterns of CAD, PAD, comorbidity,
and clinical presentation.
Prophylactic myocardial revascularization prior
to high-risk vascular surgery may be considered
in stable patients if they have persistent signs
of extensive ischaemia or a high cardiac risk.
Class a
Level b
Ref. c
I
B
[123]
I
B
[123]
I
C
IIb
B
[155]
a
Class of recommendation.
Level of evidence.
c
References.
CABG = coronary artery bypass grafting; CAD = coronary artery disease;
PAD = peripheral arterial disease; PCI = percutaneous coronary intervention.
b
Renal artery disease
Although the prevalence of atherosclerotic renal artery
stenosis in CAD patients has been reported to be as high
as 30%, its management in patients needing myocardial
revascularization is uncertain. Stented angioplasty has been
current practice in the majority of cases. Weak evidence
suggests that similar kidney function but better blood
pressure outcomes have been achieved by percutaneous
renal artery intervention. However, a recent RCT comparing
stenting with medical treatment vs. medical treatment
alone, in patients with atherosclerotic renal artery stenosis
and impaired renal function, showed that stent placement
had no favourable effect on renal function and led to a small
number of procedure-related complications [156]. Despite
a high procedural success rate of renal artery stenting,
an improvement in hypertension has been inconsistent and
the degree of stenosis that justifies stenting is unknown.
Given the relatively small advantages of angioplasty over
antihypertensive drug therapy in the treatment of hypertension, only patients with therapy-resistant hypertension
and progressive renal failure in the presence of functionally
significant renal artery stenosis may benefit from revascularization. Functional assessment of renal artery stenosis
severity using pressure gradient measurements may improve
appropriate patient selection [157].
Table 25
Management of patients with renal artery stenosis
Functional assessment of renal artery stenosis
severity using pressure gradient measurements
may be useful in selecting hypertensive patients
who benefit from renal artery stenting.
Routine renal artery stenting to prevent
deterioration of renal function is not
recommended.
a
b
c
Class of recommendation.
Level of evidence.
References.
Class a
Level b
Ref. c
IIb
B
[157]
III
B
[156]
S25
Table 25 summarizes the management of patients with
renal artery stenosis.
9.5. Myocardial revascularization in chronic
heart failure
CAD is the most common cause of HF. The prognosis for
patients with chronic ischaemic LV systolic dysfunction
remains poor despite advances in various therapeutic
strategies. The established indications for revascularization
in patients with ischaemic HF pertain to patients with
angina and significant CAD [158]. The associated risk of
mortality is increased and ranges from 5 to 30%. The
management of patients with ischaemic HF without angina
is a challenge because of the lack of RCTs in this population.
In this context, the detection of myocardial viability should
be included in the diagnostic work-up of HF patients
with known CAD. Several prospective and retrospective
studies and meta-analyses have consistently shown improved
LV function and survival in patients with ischaemic
but viable myocardium, who subsequently underwent
revascularization [16]. Conversely, patients without viability
will not benefit from revascularization, and the high risk of
surgery should be avoided. Patients with a severely dilated
LV have a low likelihood of showing improvement in LVEF
even in the presence of substantial viability. The possibility
of combining myocardial revascularization with surgical
ventricular reconstruction (SVR) to reverse LV remodelling
has been addressed in a few RCTs [159]. The aim of SVR is to
exclude scar tissue from the LV wall, thereby restoring the
LV physiological volume and shape.
The Surgical Treatment IsChaemic Heart failure (STICH)
Hypothesis 2 substudy compared CABG alone with combined
CABG and SVR in patients with LVEF 35% [159]. No
difference in the occurrence of the primary outcome
(death from any cause or hospitalization for cardiac causes)
between the CABG and the combined procedure groups was
observed. However, the combined procedure resulted in
a 16 mL/m2 (19%) reduction in end-systolic volume index,
larger than in the CABG-only group, but smaller than
in previously reported observational studies. The latter
observation raises concerns about the extent of the SVR
procedure that was applied in this RCT [160]. Choosing to
add SVR to CABG should be based on a careful evaluation
of patients, including symptoms (HF symptoms should be
predominant over angina), measurements of LV volumes,
assessment of the transmural extent of myocardial scar
tissue, and should be performed only in centres with
a high level of surgical expertise. In this context, MRI
is the standard imaging technique to assess myocardial
anatomy, regional and global function, viability, and, more
importantly, infarct size and percentage of transmurality
determined by late gadolinium enhancement.
The choice between CABG and PCI should be based on
a careful evaluation of the anatomy of coronary lesions,
expected completeness of revascularization, comorbidities,
and associated significant valvular disease [141]. Data on PCI
results in patients with ischaemic HF but without angina
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 26
Recommendations for patients with chronic heart failure and systolic left
ventricular dysfunction (ejection fraction 35%), presenting predominantly
with anginal symptoms
CABG is recommended for:
• significant LM stenosis
• LM equivalent (proximal stenosis of both
LAD and LCx)
• proximal LAD stenosis with 2- or 3-vessel
disease.
CABG with SVR may be considered in patients
with LVESV index 60 mL/m2 and scarred LAD
territory.
PCI may be considered if anatomy is suitable,
in the presence of viable myocardium.
Class a
Level b
Ref. c
I
B
[158]
IIb
B
[159,
160]
IIb
C
a
Class of recommendation.
Level of evidence.
c
References.
CABG = coronary artery bypass grafting; LAD = left anterior descending;
LCx = left circumflex; LM = left main; LVESV = left ventricular end-systolic
volume; PCI = percutaneous coronary intervention; SVR = surgical ventricular
reconstruction.
b
Table 27
Recommendations for patients with chronic heart failure and systolic left
ventricular dysfunction (ejection fraction 35%), presenting predominantly
with heart failure symptoms (no or mild angina: Canadian Cardiovascular
Society 1 2)
LV aneurysmectomy during CABG is indicated
in patients with a large LV aneurysm.
CABG should be considered in the presence of
viable myocardium, irrespective of LVESV.
CABG with SVR may be considered in patients
with a scarred LAD territory.
PCI may be considered if anatomy is suitable,
in the presence of viable myocardium.
Revascularization in the absence of evidence
of myocardial viability is not recommended.
Class a
Level b
Ref. c
I
C
IIa
B
[16]
IIb
B
[159,
160]
IIb
C
III
B
[16]
a
Class of recommendation.
Level of evidence.
References.
CABG = coronary artery bypass grafting; LAD = left anterior descending;
LV = left ventricle; LVESV = left ventricular end-systolic volume;
PCI = percutaneous coronary intervention; SVR = surgical ventricular
reconstruction.
b
c
are limited. There is weak evidence suggesting that CABG
is superior to PCI [36].
Many CAD patients with depressed LV function remain at
risk of sudden cardiac death (SCD) despite revascularization
and potential indications for implantable cardioverter
defibrillator (ICD) therapy should be carefully examined
(Section 9.7.3) [93].
Tables 26 and 27 summarize the recommendations for
patients with CHF and systolic LV dysfunction (EF 35%),
presenting predominantly with anginal symptoms or with HF
symptoms, respectively.
grafts [161]. In symptomatic patients, early graft failure can
be identified as the cause of ischaemia in ~75% of cases,
while pericarditis or prolonged spasm is diagnosed in the
remainder. PCI in acute post-operative graft failure may be
an alternative to re-operation with acceptable results and
fewer complications [161]. The target for PCI is the body of
the native vessel or of the ITA graft while freshly occluded
SVG or the anastomosis itself should not be targeted due
to the risk of embolization or perforation. Surgery should
be favoured if the graft or native artery appears unsuitable
for PCI, or if several important grafts are occluded. In
asymptomatic patients, re-operation or PCI should only be
considered if the artery is of good size, severely narrowed
and supplies a large territory of myocardium. Redo CABG or
PCI should be decided by the Heart Team.
9.6.2. Revascularization for late graft failure
Ischaemia after CABG may be due to new disease,
progression beyond the bypass graft anastomosis, or disease
in the graft itself (Table 28).
Repeat revascularization in patients with graft failure
is indicated in the presence of severe symptoms despite
anti-anginal medication, and in patients with mild or no
symptoms depending on risk stratification by non-invasive
testing [32,164].
Redo coronary artery bypass grafting or percutaneous
coronary intervention
PCI in patients with previous CABG has worse acute and
long-term outcomes than in patients without prior CABG.
Patients who undergo repeat CABG have a two- to four-fold
higher mortality than for the first procedure [165,166]. A
large series of the Cleveland Clinic Foundation showed that
the risk of re-operation was mainly driven by comorbidity
and less by the re-operation itself [165].
There are limited data comparing the efficacy of PCI vs.
redo CABG in patients with previous CABG. In a propensity
analysis of long-term survival after redo CABG or PCI
in patients with MVD and high-risk features, short-term
outcome after either technique was very favourable, with
nearly identical survival at 1 and 5 years [32]. In the
AWESOME RCT and registry, overall in-hospital mortality was
higher with CABG than with PCI [167,168].
Because of the initial higher mortality of redo CABG and
the comparable long-term mortality, PCI is the preferred
revascularization strategy in patients with patent left ITA
and amenable anatomy. CABG is preferred for patients
with more diseased or occluded grafts, reduced systolic LV
function, more total occlusion of native arteries, as well as
absence of a patent arterial graft [32]. The ITA is the conduit
of choice for revascularization during redo CABG [169].
Table 28
Graft patency after coronary artery bypass grafting (%)
9.6. Crossed revascularization procedures
9.6.1. Revascularization for acute graft failure
Early graft failure after CABG (<1 month) may occur in
8 30% of cases. Perioperative angiography showed failure
of 8% of saphenous vein grafts (SVGs) and 7% of left ITA
a
Graft
Patency at
1 year
Patency at
4 5 years
Patency at
10 15 years
Ref. a
SVG
Radial artery
Left ITA
Right ITA
>90
86 96
>91
Not reported
65 80
89
88
96
25 50
Not reported
88
65
[47,162]
[162,163]
[161,162]
[162]
References.
ITA = internal thoracic artery; SVG = saphenous vein graft.
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 29
Crossed revascularization procedures
Following CABG
In early graft failure
Coronary angiography is indicated for highly symptomatic patients, or in the event of post-operative instability, or with
abnormal biomarkers/ECG suggestive of perioperative MI.
Decision of redo CABG or PCI should be made by the Heart Team.
PCI is a superior alternative to re-operation in patients with early ischaemia after CABG.
The preferred target for PCI is the native vessel or ITA graft, not the freshly occluded SVG.
For freshly occluded SVG, redo CABG is recommended rather than PCI if the native artery appears unsuitable for PCI or
several important grafts are occluded.
In late graft failure following CABG
PCI or redo CABG is indicated in patients with severe symptoms or extensive ischaemia despite OMT.
PCI is recommended as a first choice, rather than redo CABG.
PCI of the bypassed native artery is the preferred approach when stenosed grafts >3 years old.
ITA is the conduit of choice for redo CABG.
Redo CABG should be considered for patients with several diseased grafts, reduced LV function, several CTO, or absence
of a patent ITA.
PCI should be considered in patients with patent left ITA and amenable anatomy.
Following PCI
In early failure following PCI
Repeat PCI is recommended for early symptomatic restenosis after PCI.
Immediate CABG is indicated if failed PCI is likely to cause a large MI.
In late failure following PCI
Patients with intolerable angina or ischaemia will eventually require CABG if:
(a) lesions are unsuitable for PCI.
(b) there is additional non-discrete disease progression in other vessels.
(c) restenoses are repetitive and interventional options are not favourable.
Class a
Level b
I
C
I
I
I
I
C
B
C
C
I
I
I
I
IIa
B
B
B
B
C
IIa
C
I
I
B
C
I
I
I
C
C
C
Ref. c
[161]
[32,164]
[32,165 168]
[170]
[169]
[173 175]
a
Class of recommendation.
Level of evidence.
c
References.
CABG = coronary artery bypass grafting; CTO = chronic total occlusion; ECG = electrocardiogram; ITA = internal thoracic artery; LV = left ventricle; MI = myocardial
infarction; OMT = optimal medical therapy; PCI = percutaneous coronary intervention; SVG = saphenous vein graft.
b
Lesion subsets
Embolic complications and restenosis are significantly
more frequent with SVG PCI than after ITA or native
vessel PCI [170]. TVR in SVG intervention is driven mainly
by progression in the non-target areas. Immediate results
improve with protection devices but the efficacy of DES is
less than with native vessel PCI [171].
PCI of the bypassed native artery should be the preferred
approach provided the native vessel is not chronically
occluded. PCI of a CTO may be indicated when ischaemic
symptoms are present and there is evidence of significant
ischaemia and viable myocardium in the territory supplied.
CTO interventions should be performed by specialized
operators with >80% success rates. If PCI of the native vessel
fails, angioplasty of the stenosed SVG remains an option. In
chronically occluded SVG the success rates are considerably
lower with even higher complication and restenosis rates
than in non-occluded SVG [32].
9.6.3. Revascularization for acute failure after
percutaneous coronary intervention
If repeat PCI fails to abort evolving significant MI, immediate
CABG is indicated [172]. When severe haemodynamic
instability is present, IABP should be inserted prior to
emergency revascularization. Cardiopulmonary assistance
may be considered if the patient does not stabilize prior
to emergency CABG.
9.6.4. Elective revascularization for late failure after
percutaneous coronary intervention
Late failure after PCI is mostly due to restenosis and
occasionally to (very) late stent thrombosis. Significant
restenosis is commonly treated by PCI (balloon, DES, or
drug-eluting balloon). Patients with intolerable angina or
ischaemia will eventually require CABG, especially with
unsuitable morphology for PCI (e.g. very long restenosis),
additional non-discrete disease progression in other vessels
or repetitive restenosis without favourable options for
PCI. Diabetes, number of diseased vessels, type of lesion,
lesion topography, and incomplete PCI revascularization
have been identified as risk factors for subsequent CABG
after PCI. Arterial grafts should be used preferentially to
treat restenotic vessels. According to several studies, the
operative risk of CABG may be increased, as compared
with CABG without prior PCI. Prior stenting may compel
more distal bypass grafting with less favourable results.
Registry data showed increased complications after CABG
with multiple prior PCI procedures.
9.6.5. Hybrid procedures
Hybrid myocardial revascularization is a planned, intentional
combination of CABG, with a catheter-based intervention
to other coronary arteries during the same hospital stay.
Procedures can be performed consecutively in a hybrid
operating room, or sequentially on separate occasions in the
conventional surgical and PCI environments.
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 30
Crossed revascularization procedures
Hybrid procedure, defined as consecutive
or combined surgical and interventional
revascularization may be considered in
specific patient subsets at experienced
centres.
a
b
c
Class a
Level b
Ref. c
IIb
B
[176,177]
Class of recommendation.
Level of evidence.
References.
Hybrid procedure consisting of ITA to LAD and PCI of other
territories appears reasonable when PCI of the LAD is not
an option or unlikely to portend good results (Table 30).
Indications should be selected by the Heart Team and
potential opportunities for using a hybrid approach are listed
here.
(1) Primary PCI for posterior or inferior STEMI and severe
CAD in non-culprit vessel(s), better suited for CABG.
(2) Emergent PCI prior to surgery in patients with combined
valvular and coronary disease, if the patient cannot
be transferred for surgery, or in the presence of acute
ischaemia.
(3) Patients who had previous CABG and now require valve
surgery and who have at least one important patent graft
(e.g. ITA to LAD) and one or two occluded grafts with a
native vessel suitable for PCI.
(4) Combination of revascularization with non-sternotomy
valve intervention (e.g. PCI and minimally invasive
mitral valve repair, or PCI and trans-apical aortic valve
implantation).
(5) In patients with conditions likely to prevent healing
after sternotomy, surgery can be restricted to the LAD
territory using minimally invasive direct coronary artery
bypass (MIDCAB) left ITA grafting. Remaining lesions in
other vessels are treated by PCI.
9.7. Arrhythmias in patients with ischaemic
heart disease
9.7.1. Atrial fibrillation
Atrial fibrillation in patients scheduled for coronary
artery bypass grafting
The presence of AF in patients scheduled for CABG is
independently associated with increased late cardiac morbidity and mortality and poor long-term prognosis [178,179].
Therefore, concomitant ablative treatment of AF during
surgery may be considered in those patients although no
prospective RCT has addressed this issue. All available
studies are limited by small sample size or short follow-up
periods.
Several ablation techniques have been proposed including
the Corridor procedure, the Radial maze procedure, and the
Cox-maze I III. Currently, most groups favour the creation
of ablation lines using a variety of energy sources including
radiofrequency energy, microwave, cryoablation, laser, and
high-intensity focused ultrasound. The success rates depend
upon transmurality and contiguity of the ablation lines,
completeness of the lesion pattern, and evaluation method
(ECG or Holter monitoring). Best reported results, between
65% and 95% at 6 months, have used bipolar radiofrequency
current and more extensive left atrium (LA) and bi-atrial
lesions [180]. Poor chances of success include large LA
size and pre-operative permanent AF duration. Complete
exclusion of the LA appendage may be considered during
a surgical ablation procedure to reduce the risk of stroke.
Atrial fibrillation after coronary artery bypass grafting
AF occurs in 27 40% of cases early after cardiac surgery
and is associated with infection, renal failure, neurological
complications, prolonged hospital stay, and increased cost.
Risk factors for developing post-operative AF include
advanced age, need for prolonged ventilation (24 h), CPB,
chronic obstructive lung disease, and pre-operative arrhythmias. Because an exaggerated inflammatory response is a
possible aetiological factor, treatment with corticosteroids
either as a single intravenous (i.v.) injection [181] or as
oral prophylaxis, has been applied. Methylprednisolone (1 g)
before surgery and dexamethasone (4 mg every 6 h) for
24 h significantly reduced the incidence of new-onset AF in
two RCTs but possibly at the cost of more post-operative
complications [181,182].
b-blockers, sotalol, and amiodarone reduce the risk of
post-operative AF [183,184]. There is a wealth of safety
and efficacy data, including two recent meta-analyses,
supporting the routine use of b-blockers in post-operative
cardiac surgical patients to reduce the incidence of
post-operative AF (OR 0.36, 95% CI 0.28 0.47) [185,186].
Dosages vary widely between trials based on body
size and LV function. As shown by several RCTs and
meta-analyses [183,184,186], amiodarone is effective for
the prophylaxis of AF. The largest RCT reported atrial
tachyarrhythmias in 16.1% of amiodarone-treated patients
compared with 29.5% of placebo-treated patients (HR 0.52,
95% CI 0.34 0.69), a 13.4% absolute risk reduction [184].
However, amiodarone trials excluded patients with low
resting heart rate, second or third degree atrioventricular
block, or New York Heart Association (NYHA) class III or IV.
Table 31
Prevention and treatment of atrial fibrillation with coronary artery bypass
grafting
b-blockers are recommended to
decrease the incidence of AF
after CABG.
Sotalol should be considered to decrease
the incidence of AF after CABG.
Amiodarone should be considered
to decrease the incidence of AF
after CABG.
Statins should be considered to decrease
the incidence of AF after CABG.
Corticosteroids may be considered
to decrease the incidence of AF
after CABG.
Restoring sinus rhythm in patients
having CABG may be considered in order
to increase survival.
Performing AF ablation during CABG may
be considered an effective strategy.
a
Class a
Level b
Ref. c
I
A
[185,186,189,
190]
IIa
A
[183,185,186]
IIa
A
[183,184,186]
IIa
B
[187,188]
IIb
B
[181,182]
IIb
B
[178,179]
IIb
C
Class of recommendation.
Level of evidence.
References.
AF = atrial fibrillation; CABG = coronary artery bypass grafting.
b
c
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Two RCTs evaluating the effect of statin pre-treatment
suggested effectiveness in preventing post-operative AF,
possibly through anti-inflammatory effects (OR 0.57, 95% CI
0.42 0.77) [187,188].
Table 31 summarizes the recommendations concerning
the prevention and treatment of atrial fibrillation in CABG
patients.
Percutaneous coronary intervention and atrial
fibrillation
In patients with paroxysmal AF it is worthwhile to rule
out ischaemia as a potential cause. A high prevalence
of obstructive CAD was observed among patients with
AF undergoing systematic multislice CT, confirming the
hypothesis that AF could be a marker of advanced coronary
atherosclerosis. Issues related to antiplatelet therapy in
patients under anticoagulants are discussed in Section 12.4.
9.7.2. Supraventricular arrhythmias other than atrial
fibrillation or flutter
The relationship between supraventricular arrhythmia other
than AF and/or atrial flutter and CAD is unclear. During
supraventricular tachycardia episodes, ECG changes and
clinical symptoms suggestive of cardiac ischaemia may be
present. Screening for CAD should be restricted to patients
with typical symptoms outside arrhythmia episodes, who
have a high-risk profile or increasing frequency of arrhythmia
episodes [191].
Because of the effectiveness of percutaneous catheter ablation techniques for the treatment of accessory pathways,
such as in Wolff Parkinson White syndrome, surgery should
be restricted to patients after failed catheter ablation,
with complex congenital heart disease or scheduled for
valve surgery. Anti-arrhythmic surgical procedures should be
performed in experienced centres.
9.7.3. Ventricular arrhythmias
In the setting of transient cardiac ischaemia, within 24 48 h
of ACS, during primary PCI for STEMI or late after MI,
ventricular arrhythmias are a major cause of death. Large
RCTs have shown a beneficial effect of ICD therapy in
survivors of life-threatening arrhythmias and in patients at
risk of sudden death (primary prevention).
Primary prevention
Patients with LVEF 35% are at risk of sudden cardiac
death and may benefit from ICD therapy. However, screening
for and treating cardiac ischaemia is required prior to
ICD implantation because LV function may recover after
revascularization of viable myocardium [16]. ICD therapy
should be postponed for at least 3 months after PCI or
CABG to allow time for LV recovery. In patients with
large scar areas, recovery of LVEF is less likely and ICD
implantation may be considered appropriate shortly after
revascularization.
Secondary prevention
Patients surviving out-of-hospital cardiac arrest are at
high risk of recurrence. Prevention of potentially lethal
recurrence starts with a systematic evaluation of the
underlying pathology and the subsequent risk for recurrence,
S29
to allow the implementation of an individualized treatment
plan.
Ventricular arrhythmias are associated with acute or
chronic CAD. Revascularization of hibernating myocardium
may improve electrical stability and reduces the likelihood of ventricular arrhythmias. However, several studies
demonstrated that a significant number of patients remained
arrhythmia inducible after revascularization resulting in a
13% SCD rate. Patients are candidates for ICD therapy if
revascularization cannot be achieved or in the case of prior
MI with significant LV dysfunction.
In patients with monomorphic sustained ventricular
tachycardia (VT), revascularization may help to lower the
number of recurrences but is not considered to be sufficient
and ICD implantation is the first line of SCD prevention.
However, percutaneous endo- or epicardial catheter ablation
procedures are becoming increasingly successful and may be
considered in patients with haemodynamically stable VT.
9.7.4. Concomitant revascularization in heart failure
patients who are candidates for resynchronization
therapy
In patients scheduled for cardiac resynchronization therapy
(CRT) or CRT combined with ICD therapy, having concomitant
cardiac surgery (a revascularization procedure or LV reconstruction/valve repair), epicardial LV lead implantation may
be considered. Potential advantages include avoidance of
subsequent transvenous LV lead placement and convenient
selection of the preferred lead location. When operating on
already implanted patients, the ICD should be switched off.
In patients having PCI, the ICD should be implanted first to
avoid DAPT discontinuation.
10. Procedural aspects of coronary artery
bypass grafting
10.1. Pre-operative management
Patients admitted for surgical revascularization are usually
taking many medicines including b-blockers, ACE inhibitors,
statins, and antiplatelet drugs. b-blockers should not be
stopped to avoid acute ischaemia upon discontinuation.
10.2. Surgical procedures
Surgical procedures are complex interactions between
human and material resources. The best performance is
obtained through experience and routine, process control,
case-mix, and volume load. The surgical procedure is
performed within a hospital structure and by a team
specialized in cardiac surgery. The surgical, anaesthesiological, and intensive care procedures are written down in
protocols [192].
The initial development of CABG was made possible with
the use of extracorporeal circulation and induced ventricular
fibrillation. When aortic cross-clamping is used to perform
the distal anastomoses, the myocardium can be protected
against ensuing ischaemia by several methods.
CABG is performed using extracorporeal circulation (CPB)
in 70% of all operations worldwide. This includes a median
sternotomy, ITA(s) dissection, and, when appropriate,
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
simultaneous harvesting of the venous and or radial
artery grafts. Endoscopic vein-graft harvesting cannot be
recommended at present as it has been associated with veingraft failure and adverse clinical outcomes. CPB requires
profound anticoagulation using heparin for an activated
clotting time >400 s.
Partial or total aortic cross-clamping allows the construction of proximal anastomoses. A single cross-clamp
may be preferred with the aim of reducing atheroembolic
events. Epiaortic ultrasonography, visualizing atherosclerotic plaques, can modify the surgical approach but was not
shown to reduce the incidence of cerebral emboli [193].
10.2.1. Coronary vessel
CABG aims to revascularize coronary arteries, with a flowreducing luminal stenosis, supplying a viable and sizeable
area at risk. The most frequently grafted coronary arteries
are the epicardial vessels, but intramural grafting is part of
routine coronary surgery.
The patency of a constructed graft is influenced by
characteristics of the anastomosed vessel, the outflow
area, the graft material, its manipulation and construction.
Important coronary characteristics are the internal lumen
size, the severity of proximal stenosis, the quality of the
wall at the site of anastomosis, and the distal vascular bed.
Diffuse CAD is often seen in the presence of insulin-treated
diabetes, long-standing and untreated hypertension, PAD,
and CKD.
Different technical approaches have been applied to vessels with diffuse pathology such as very long anastomoses,
patch reconstruction of the vessel roof with or without
grafting to this roof, coronary endarterectomy, and multiple
anastomoses on the same vessel, with no evidence of
superiority of any one.
10.2.2. Bypass graft
The long-term benefit of CABG is maximized with the
use of arterial grafts, specifically the ITA [194]. Available
grafts include internal thoracic, radial, and gastro-epiploïc
arteries. All except the radial artery can remain connected
to their anatomical inflow or be used as free graft, with the
aorta or another graft as inflow.
The side-to-side anastomosis used in arterial and venous
grafting eliminates an aortic anastomosis, decreases the
amount of graft required, and increases total graft flow.
The latter factor contributes to a higher patency rate.
Partially or total ITA skeletonization increases its length
and possibility of use. Rates of sternal wound infection and
angiographic results are similar whether ITA is skeletonized
or not. These techniques may allow a complete arterial
revascularization.
Use of bilateral ITA is associated with higher postoperative sternal dehiscence and increased rate of mediastinitis in obese and possibly diabetic patients [195]. But
event-free long-term survival, reduced risk of recurrent
angina or MI, and reduced need for re-operation correlate
well with the extensive use of arterial grafts [49,196,197].
Using radial artery grafts increases the number of arterial
anastomoses beyond the use of both ITAs. At 5 years, patency
rates of radial artery are possibly superior to saphenous
Table 32
Technical recommendations for coronary artery bypass grafting
Procedures should be performed in a hospital
structure and by a team specialized in
cardiac surgery, using written protocols.
Arterial grafting to the LAD system is
indicated.
Complete revascularization with arterial
grafting to non-LAD coronary systems is
indicated in patients with reasonable life
expectancy.
Minimization of aortic manipulation is
recommended.
Graft evaluation is recommended before
leaving the operating theatre.
Class a
Level b
Ref. c
I
B
[192,196]
I
A
[194]
I
A
[49,194,
196,197,
199]
I
C
I
C
a
Class of recommendation.
Level of evidence.
c
References.
LAD = left anterior descending.
b
grafts but certainly inferior to ITA. This patency is strongly
related to target vessel size and stenosis severity.
Graft flow measurement, related to graft type, vessel
size, degree of stenosis, quality of anastomosis, and outflow
area, is useful at the end of surgery. Flow <20 mL/min
and pulsatility index >5 predict technically inadequate
grafts, mandating graft revision before leaving the operating
theatre [198].
Table 32 lists the evidence-based technical recommendations for CABG.
10.3. Early post-operative risk
Early clinical outcome at 3 months after CABG is characterized by a 1 2% mortality rate and a 1 2% morbidity rate for
each of the following events: stroke, renal, pulmonary and
cardiac failure, bleeding, and wound infection. The early
risk interval in CABG extends for 3 months, is multifactorial,
and depends on the interface between technical variability
and patient comorbidity [197].
The survival outcome for all CABG operations performed
in the UK in the 2004 08 period showed a 1.1% hospital
mortality in 78 367 elective patients vs. 2.6% in 32 990 urgent
patients [200]. In all patients without and 30 218 patients
with LM stenosis, the respective mortalities were 1.5%
and 2.5% (respective predicted elective mortalities 0.9%
and 1.5%). In all patients without or 26 020 patients with
diabetes, the respective mortalities were 1.6% and 2.6%
(with respective predicted elective mortalities 1.0% and
1.6%).
Despite improved techniques and experience, part of
the morbidity is caused by the extracorporeal circulation,
prompting the off-pump approach. Complete off-pump
procedures in the hands of trained surgical teams seem to
be associated with a reduced risk of stroke, AF, respiratory
and wound infections, less transfusion, and shorter hospital
length of stay [201]. Highly experienced teams obtain similar
1-year outcomes, graft patency, and quality of life with offpump vs. on-pump approaches. Thus, currently available
data remain conflicting perhaps due to differences in patient
selection and/or procedural techniques [202].
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
11. Procedural aspects of percutaneous
coronary intervention
11.1. Impact of clinical presentation
Percutaneous coronary intervention for stable
coronary artery disease
Proper patient information and preparation are mandatory
for all PCI procedures, including elective and ad hoc
interventions in patients with stable CAD (Section 4).
Depending on the severity of the stenosis and in the absence
of extensive calcification, many stable, non-occlusive lesions
can be directly stented, without pre-dilatation. Severely
fibrotic or calcified lesions, especially if they cannot be
crossed by a balloon after successful wiring or be adequately
dilated with non-compliant balloons despite high inflation
pressure, may require pre-treatment with rotablation [55].
Acute ischaemia due to coronary dissection can be corrected
with stents and emergency CABG is necessary in <0.1%.
Percutaneous coronary intervention for acute coronary
artery disease
Various approaches have been evaluated to prevent distal
embolization during PCI for unstable CAD. Although the
concept of preventing embolization of thrombus or debris
seems very rational, initial trials testing a variety of
different concepts could not establish its clinical usefulness.
A meta-analysis including 1467 STEMI patients enrolled
in eight RCTs showed no difference in terms of blood
flow normalization rate in the culprit epicardial vessel
between patients allocated to distal protection devices
or controls [203]. Therefore, the systematic use of distal
protection devices cannot be recommended for PCI in lesions
with a high thrombotic burden.
One limitation of distal placement of occlusive balloons
or filters beyond thrombus-containing lesions is the obvious
need to penetrate the thrombus at the risk of detaching
small particles. Alternative devices that allow immediate
suction are potentially more useful. There is evidence
of benefit for direct catheter aspiration of thrombus in
STEMI [204 206]. The TAPAS trial assigned 1071 patients
to catheter-based thrombus aspiration (Export aspiration
catheter) followed by primary PCI or conventional primary
PCI [207]. Patients randomized to thrombus aspiration
had a significantly higher rate of complete ST-segment
resolution and improved myocardial blush grade. Although
not powered to evaluate clinical outcome, cardiac mortality
at 1 year was reduced (3.6% vs. 6.7%) [208]. Aspiration was
performed in 84% of the patients, PCI was not performed
in 6%, and no significant improvement in peak creatine
kinase enzymes was noted. The results of the singlecentre TAPAS RCT are confirmed by several smaller studies
and meta-analyses. Therefore, the recommendation for
systematic manual thrombus aspiration during primary PCI
has been upgraded [94,204 208].
Treatment of ‘no reflow’
No-reflow or slow-flow may occur as a consequence
of downstream microvascular embolization of thrombotic
or atheromatous (lipid-rich) debris and cause reperfusion
injury. Reversing no-reflow is associated with a favourable
S31
effect on LV remodelling even in the absence of significant
improvement in regional contractile function. Intracoronary
administration of vasodilators such as adenosine, verapamil,
nicorandil, papaverine, and nitroprusside during and after
primary PCI improves flow in the infarct-related coronary
artery and myocardial perfusion and/or reduces infarct size,
but large RCTs are lacking [55]. High-dose i.v. adenosine
infusion was also associated with a reduction in infarct size,
but clinical outcomes were not significantly improved [209].
11.2. Specific lesion subsets
Bifurcation stenosis
Coronary stenoses are frequently located at bifurcations
and bifurcation lesions still represent a major challenge
for PCI, in terms of both procedural technique and clinical
outcome. Bifurcation lesions are best described according
to the Medina classification. Despite many attempts with
a variety of different stenting techniques (T-stenting,
V-stenting, crush, and its modifications, culotte, etc.),
the optimal strategy for every anatomical subset has
not yet been established. Variables to be considered are
plaque distribution, size and downstream territory of each
vessel (main and side branch), and the bifurcation angle.
Stent implantation in the main vessel only, followed by
provisional angioplasty with or without stenting of the
side branch, seems preferable compared with routine
stenting of both vessels. FFR data from side branches
suggest that angiography overestimates the functional
severity of side branch stenosis. Final kissing balloon
dilatation is recommended when two stents are eventually
required. Several stents designed specifically for treatment
of bifurcation lesions have undergone extensive evaluation
with good angiographic and clinical results, especially with
side branch size >2.5 mm. Comparative RCTs vs. provisional
stenting are lacking.
The above comments apply to PCI of (unprotected) LM
lesions, when indicated (Section 6). For bifurcation and LM
lesions, DES are preferred with special attention to adequate
sizing and deployment. For treatment of small vessels
(<2.5 mm), DES with strong antiproliferative properties (late
lumen loss 0.2 mm) are preferred to reduce restenosis
rates [210].
Chronic total coronary occlusion
CTO is defined as TIMI 0 flow for >3 months. Following the
negative results of two RCTs addressing the usefulness of
opening occluded culprit coronary arteries in the early postMI phase [90,91,211], there is some confusion regarding the
indications for PCI in ‘chronic’ total occlusions. In asymptomatic patients within 3 28 days after MI, the OAT trial
showed no survival advantage from PCI and less recurrent MI
with the conservative approach [90,211]. The results of OAT
do not necessarily pertain to CTOs. Observational studies
suggest that a successfully revascularized CTO confers a
significant 5- and 10-year survival advantage compared with
failed revascularization. A New York State survey showed
that incomplete revascularization by PCI leaving untreated
CTOs led to higher 3-year mortality [199]. Thus, similar to
non-chronically occluded vessels, revascularization of CTO
may be considered in the presence of angina or ischaemia
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 33
Recommendations for specific percutaneous coronary intervention devices and pharmacotherapy
FFR-guided PCI is recommended for detection of ischaemia-related lesion(s) when objective evidence of vessel-related
ischaemia is not available.
DES d are recommended for reduction of restenosis/re-occlusion, if no contraindication to extended DAPT.
Distal embolic protection is recommended during PCI of SVG disease to avoid distal embolization of debris and
prevent MI.
Rotablation is recommended for preparation of heavily calcified or severely fibrotic lesions that cannot be crossed by a
balloon or adequately dilated before planned stenting.
Manual catheter thrombus aspiration should be considered during PCI of the culprit lesion in STEMI.
For PCI of unstable lesions, i.v. abciximab should be considered for pharmacological treatment of no-reflow.
Drug-eluting balloons d should be considered for the treatment of in-stent restenosis after prior BMS.
Proximal embolic protection may be considered for preparation before PCI of SVG disease.
For PCI of unstable lesions, intracoronary or i.v. adenosine may be considered for pharmacological treatment of
no-reflow.
Tornus catheter may be used for preparation of heavily calcified or severely fibrotic lesions that cannot be crossed by a
balloon or adequately dilated before planned stenting.
Cutting or scoring balloons may be considered for dilatation of in-stent restenosis, to avoid slipping-induced
vessel trauma of adjacent segments.
IVUS-guided stent implantation may be considered for unprotected left main PCI.
Mesh-based protection may be considered for PCI of highly thrombotic or SVG lesions.
For PCI of unstable lesions, intracoronary nitroprusside or other vasodilators may be considered for pharmacological
treatment of no-reflow.
Class a
Level b
Ref. c
I
A
[15,28]
I
I
A
B
[45,46,55,215]
[171,213]
I
C
IIa
IIa
IIa
IIb
IIb
A
B
B
B
B
IIb
C
IIb
C
IIb
IIb
IIb
C
C
C
[204 208]
[55,209,212]
[174,175]
[214]
[209]
a
Class of recommendation.
Level of evidence.
References.
d
Recommendation is only valid for specific devices with proven efficacy/safety profile, according to the respective lesion characteristics of the studies.
DAPT = dual antiplatelet therapy; DES = drug-eluting stent; FFR = fractional flow reserve; IVUS = intravascular ultrasound; MI = myocardial infarction;
PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction; SVG = saphenous vein graft.
b
c
related to the corresponding territory. The potential longterm risk of radiation exposure should be considered.
Ad hoc PCI is not recommended for CTOs. Success rates
are strongly dependent on operator skills, experience with
specific procedural techniques, and availability of dedicated
equipment (specialized guidewires and catheters, such as
the Tornus catheter or very low profile CTO balloons).
Bilateral angiography and intravascular ultrasound (IVUS)
imaging can be very helpful as well as special techniques
such as guide anchoring, various retrograde approaches, and
specific wiring manipulation techniques. Experience with
proper management of coronary perforation and cardiac
tamponade is required.
Saphenous vein graft disease
Patients undergoing PCI of SVG are particularly at risk
of distal coronary embolization with increased risk of
peri-procedural MI [170]. PCI of de novo SVG stenosis is
considered a high-risk intervention because SVG atheroma
is friable and more prone to distal embolization. A pooled
analysis of five RCTs shows that GPIIb IIIa inhibitors are less
effective for SVG PCI than for PCI of native vessels [212].
Many different approaches have been evaluated to prevent
distal embolization of particulate debris, including distal
blocking/aspirating, proximal blocking, suction, filtering, or
mesh-based devices [171]. Unlike occlusive devices, distal
protection using filters offers the inherent advantage of
maintaining antegrade perfusion and the opportunity for
contrast injections. Combined data, mostly from comparative studies between devices and surrogate endpoints,
support the use of distal embolic protection during SVG
PCI [213,214]. Distal filters function better in SVG than in
native coronary vessels where embolization may occur in
side branches that originate proximal to the protection filter.
For SVG, the main limitation of filter devices is the absence
of a proper landing zone, when a stenosis is located close to
the distal graft anastomosis. Experience with mesh-covered
stents is limited.
In-stent restenosis
Although plain balloon angioplasty is safe for the
treatment of in-stent restenosis, it is associated with high
recurrence rates [55]. During balloon dilatation of in-stent
restenosis, balloons tend to prolapse into proximal and
distal parts, potentially causing injury to adjacent coronary
segments. Special balloons with blades or scoring wires
reduce this risk by stabilizing the balloon during inflation.
Laser, rotablation, atherectomy, and cutting balloons have
proved to be ineffective for the treatment of in-stent
restenosis. Intracoronary brachytherapy, with either b or g
radiation, was superior to balloon dilatation for the
treatment of in-stent restenosis following BMS implantation,
albeit with increased risk for late stent thrombosis [55].
Currently, intracoronary brachytherapy is of very limited
use: restenosis rates have declined and in-stent restenoses
after BMS are treated by DES or CABG [55]. Recent
developments include the use of drug-eluting balloons (see
below).
Table 33 lists the recommendations for specific PCI devices
and pharmacotherapy.
11.3. Drug-eluting stents
Efficacy and safety of drug-eluting stents
Stainless steel stents were initially designed to treat
major dissections, avoid acute vessel closure and prevent
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 34
Recommended drug-eluting stents (in alphabetic order) that have achieved
a primary clinical or surrogate angiographic endpoint
DES
Eluted drug
Trials and references
Clinical primary endpoint reached
BioMatrix Flex
Biolimus A9
LEADERS [216]
Cypher
Sirolimus
SIRIUS [217]
Endeavor
Zotarolimus
ENDEAVOR-II, -III and -IV [218, 219]
Resolute
Zotarolimus
RESOLUTE-AC [220]
Taxus Liberté/ Paclitaxel
TAXUS-IV and -V [221,222]/
Element
PERSEUS-WH [223]
Xience V
Everolimus a
SPIRIT-III and -IV [224,225]
Angiographic primary endpoint reached
Nevo
Sirolimus
NEVO RES I [226]
Nobori
Biolimus A9
NOBORI-I Phase-1 and -2 [227,228]
Yukon
Sirolimus
ISAR-Test [229]
Selection is based on adequately powered RCT with a primary clinical or
angiographic endpoint. With the exception of LEADERS and RESOLUTE (allcomers trials), efficacy was investigated in selected de novo lesions of native
coronary arteries.
a
Promus Element device elutes everolimus from a different stent platform.
DES = drug-eluting stent.
restenosis. Coronary stents are very effective in repairing
dissections and covered stents can be life saving in cases
of coronary perforation. However, due to a 20 30% rate
of recurrence of angiographic stenosis within 6 9 months
after implantation, restenosis within BMS has often been
called the Achilles’ heel of PCI. In native vessels, DES
significantly reduce angiographic restenosis and ischaemiadriven TVR [45,215]. In RCTs, no significant differences
were observed in the long-term rates of death or MI
after DES or BMS use for either off-label or on-label
indications [45,46]. In non-randomized large registry studies,
DES use may reduce death and MI [46]. First-generation
DES are safe and efficacious for both on-label and off-label
use, when implanted in the native circulation, in spite of
a slightly increased propensity for late and very late stent
thrombosis [215]. Long-term results (5 years) are only
available for SES, PES, and zotarolimus-eluting stent (ZES).
There is, however, no class effect for DES: some DES were
shown to be harmful and others are ineffective. Until today,
>100 DES RCTs in >60 000 patients have been presented and
at least 22 DES have been granted a CE mark. It should
be recognized that the quality of the relevant RCTs is
highly variable, especially regarding statistical powering and
the selection of angiographic rather than primary clinical
endpoints [55,215]. Accordingly, a small proportion only of
the available DES can be recommended on the basis of
pivotal trials (Table 34).
Are the differences between drug-eluting stents
clinically relevant?
SES and PES have been extensively compared in numerous
subsets, including diabetes [45,115,230]. While angiographic
metrics are superior with SES, no robust clinically relevant
differences up to 5-year follow-up were convincingly
identified, except for further reduction in reintervention
rates with SES vs. PES. The extent to which reduced TVR
rates are driven in part by trial-mandated angiography
in some studies remains debatable [231]. On the other
hand, recent RCTs suggest that second-generation DES may
S33
provide superior clinical outcomes to first-generation DES.
In 3690 patients enrolled in the SPIRIT-IV trial, the primary
endpoint of target lesion failure at 1 year was significantly
lower in the Xience V group as compared with the TaxusExpress stent (4.2% vs. 6.8%) [225]. In 1800 patients enrolled
in the all-comer single-centre COMPARE trial, the primary
endpoint of ischaemia-driven TVR at 1 year was significantly
lower for Xience V as compared with Taxus-Liberté DES
(6% vs. 9%) [232]. Differences were driven in part by inhospital MI and early stent thrombosis but neither trial was
powered for these endpoints [233].
Indications for drug-eluting stent
DES with proven efficacy should be considered by default
in nearly all clinical conditions and lesion subsets, except if
there are concerns or contraindications for prolonged DAPT
(Table 35). Indications for DES in a few specific patient or
lesion subsets remain a matter of debate. In selected STEMI
patients [234,235], SES and PES were shown to be safe and
effective (TYPHOON, HORIZONS-AMI, PASEO, and ZEST-AMI)
with follow-up extending from 2 to 4 years. There is no solid
evidence that one DES provides superior clinical outcome in
patients with diabetes, due to the limited number of smallsized trials or the limitations of subgroup analyses [115].
Studies based on angiographic endpoints favour the use of
DES with strong antiproliferative properties (late lumen loss
0.2 mm) [231].
The use of DES vs. BMS for treatment of de novo lesions
in SVGs remains controversial [236].
Table 35 summarizes the relative clinical contraindications
to the use of DES.
The optimal duration of DAPT after DES implantation is
not known. Convincing data exist only for continuation up to
6 months [237]. Possibly, under some circumstances or with
some DES, DAPT for 3 months could be sufficient but the evidence is not robust [219]. Recent evidence shows that (very)
late stent thrombosis results from delayed hypersensitivity
to components of the drug polymer device combination
that causes necrotizing vasculitis and late malapposition [238]. Diabetics may require a longer duration of DAPT.
For situations listed in Table 35, a number of alternative
approaches have been tested. The Genous bio-engineered
BMS carries a layer of murine, monoclonal, antihuman
CD34 antibody, aimed at capturing circulating endothelial
CD34+ progenitor cells, possibly increasing the rate of
healing. The single-centre pilot TRIAS RCT did not confirm
initial promising results in patients at high risk of coronary
restenosis [239].
Table 35
Relative clinical contraindications to the use of drug-eluting stents
• Clinical history difficult to obtain, especially in the setting of acute
severe clinical conditions (STEMI or cardiogenic shock).
• Expected poor compliance with DAPT, including patients with multiple
comorbidities and polypharmacy.
• Non-elective surgery required in the short term that would require
interruption of DAPT.
• Increased risk of bleeding.
• Known allergy to ASA or clopidogrel/prasugrel/ticagrelor.
• Absolute indication for long-term anticoagulation.
ASA = acetylsalicylic acid; DAPT = dual antiplatelet therapy; DES = drug-eluting
stent; STEMI = ST-segment elevation myocardial infarction.
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Drug-eluting balloons
The rationale of using drug-eluting balloons is based on
the concept that with highly lipophilic drugs, even short
contact times between the balloon and the vessel wall are
sufficient for effective drug delivery. Using a paclitaxeleluting balloon, three RCTs have targeted in-stent restenosis
following BMS implantation: PACCOCATH-I and -II [174,175]
and PEPCAD-II [240]. As with DES, one cannot assume a
class effect for all drug-eluting balloons. In the randomized
PEPCAD III study, the combination of a drug-eluting balloon
with cobalt chromium stent implantation was inferior to SES
for de novo indications.
Future perspectives
Although some brands already provide a biodegradable
polymer, current DES remain permanent implants that
cannot be extracted like pacemakers or artificial heart
valves. Furthermore, stents force the cardiac surgeons
to anastomose bypass grafts more distally. Stents create
disruptive artefacts on cardiac CT and magnetic resonance
images. Therefore, fully biodegradable stents are in
development [241].
11.4. Adjunctive invasive diagnostic tools
Intravascular ultrasound imaging and optical coherence
tomography
Whereas angiography depicts only a two-dimensional
lumen silhouette, IVUS allows tomographic assessment of
lumen area, plaque size, and distribution. IVUS is a valuable
adjunct to angiography, providing further insights into
both diagnosis and therapy, including stent implantation.
Interventional cardiologists have learnt much from IVUS, but
it has been difficult to demonstrate that this knowledge
acquired routinely translates into reduced MACE. Multiple
studies have addressed the potential of IVUS to reduce
restenosis and adverse events after BMS implantation,
but conflicting results were obtained with the largest
of these trials showing no difference between groups
with or without IVUS guidance. For DES, it was recently
shown that the threshold of stent expansion predictive
of late events including restenosis and stent thrombosis
is lower than for BMS (5.0 5.5 mm2 ). In a retrospective
analysis of a multicentre registry comparing PCI with
surgery for unprotected LM, IVUS-guided stent implantation
was associated with a significant mortality reduction at
3 years [242]. No properly designed RCT has compared
the clinical value of IVUS-guided stent implantation in the
DES era.
The analysis of plaque composition based on radiofrequency backscatter, so-called ‘virtual histology’, characterizes plaques as fibrotic, fibrofatty with or without
a necrotic core, or calcific. Although the PROSPECT
trial [243] provided new insights regarding indications for
stent implantation, the role of tissue characterization for
everyday practice remains to be established.
Optical coherence tomography (OCT) is a light-based
modality of intravascular imaging with higher spatial
resolution than IVUS (15 vs. 100 mm). Its penetration is
lower than IVUS but it provides detailed imaging of the
endoluminal borders. At present, OCT is a valuable research
tool.
Pressure-derived fractional flow reserve
Although non-invasive stress imaging should be the
gold standard for evaluation of patients with known or
suspected CAD, many patients come to the catheterization
laboratory without prior functional testing. When a noninvasive imaging stress test is unavailable, FFR can be
useful, especially in the presence of MVD. The concept that
avoiding unnecessary stenting actually improves outcome
was demonstrated in the DEFER [15] and FAME [28] trials.
FFR is a valuable tool to determine whether or not
an intermediate stenotic segment can cause downstream
ischaemia in stable and unstable patients with MVD, in-stent
restenosis, LM stenosis, and post-MI.
12. Antithrombotic pharmacotherapy
Treatment of CAD patients often requires the combination
of anti-platelet and antithrombotic therapies to prevent
thrombosis from activation of both platelets and the
coagulation system. The choice, initiation, and duration of
antithrombotic strategies for myocardial revascularization
depend on the clinical setting (elective, acute, or urgent
intervention). To maximize the effectiveness of therapy
and reduce the hazard of bleeding, ischaemic and bleeding
risks should be evaluated on an individual basis. A wellvalidated score for estimating bleeding risk is eagerly
awaited.
12.1. Elective percutaneous coronary
intervention
(a) Antiplatelet therapy
DAPT includes acetylsalicylic acid (ASA) 150 300 mg per
os or 250 ( 500) mg bolus i.v. followed by 75 100 mg per os
daily for all patients plus clopidogrel 300 (600)-mg loading
dose followed by 75 mg daily for all patients [55].
Since the vast majority of PCI procedures eventually
conclude with stent implantation, every patient scheduled
for PCI should be considered for pre-treatment with
clopidogrel, regardless of whether stent implantation is
intended or not. To ensure full antiplatelet activity,
clopidogrel should be initiated at least 6 h prior to
the procedure with a loading dose of 300 mg, ideally
administered the day before a planned PCI. If this is not
possible, a loading dose of 600 mg should be administered
at least 2 h before PCI. Of note, this pre-loading strategy
was not shown to improve outcome. A 600-mg clopidogrel
loading dose may be preferable because of greater platelet
inhibition than with the 300-mg standard dose, even if this
is given >6 h before PCI. When diagnostic angiography is
negative or no intervention is performed, clopidogrel can
be stopped. When a 300-mg loading dose has been given
and ad hoc PCI is performed, another 300-mg dose can be
given. The use of a higher maintenance dose (150 mg) has
been proposed in patients with high thrombotic risk (e.g. in
diabetics, patients after recurrent MI, after early and late
stent thrombosis, for complex lesions, or in life-threatening
situations should occlusion occur). GPIIb IIIa inhibitors
should be used only in ‘bail-out’ situations (thrombus, slow
flow, vessel closure, very complex lesions) [55]. Recent
trials did not demonstrate additional benefit of GPIIb IIIa
inhibitors after a clopidogrel loading dose of 600 mg.
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ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 36
Antithrombotic treatment options in myocardial revascularization
Class a
Level b
Ref. c
ASA
Clopidogrel
Clopidogrel pretreatment with 300 mg loading dose >6 h before PCI
(or 600 mg >2 h before)
+ GPIIb IIIa antagonists (bailout situation only)
I
I
I
B
A
C
[55]
[55]
IIa
C
UFH
Enoxaparin
I
IIa
C
B
[244]
ASA
Clopidogrel (with 600 mg loading dose as soon as possible)
Clopidogrel (for 9 12 months after PCI)
Prasugrel d
Ticagrelor d
+ GPIIb IIIa antagonists
(in patients with evidence of high intracoronary thrombus burden)
Abciximab (with DAPT)
Tirofiban, Eptifibatide
Upstream GPIIb IIIa antagonists
I
I
I
IIa
I
C
C
B
B
B
[55]
[246,247]
[248]
I
IIa
III
B
B
B
[249]
[55]
[65]
UFH (+GPIIb IIIa antagonists) or
Bivalirudin (monotherapy)
UFH
Bivalirudin
Fondaparinux
Enoxaparin
Fondaparinux
Enoxaparin
I
I
I
I
I
IIa
I
IIa
C
B
C
B
B
B
B
B
ASA
Clopidogrel f (with 600 mg loading dose as soon as possible)
Prasugrel d
Ticagrelor d
+ GPIIb IIIa antagonists (in patients with evidence of high intracoronary thrombus burden)
Abciximab
Eptifibatide
Tirofiban
Upstream GPIIb IIIa antagonists
I
I
I
I
B
C
B
B
[55,94]
IIa
IIa
IIb
III
A
B
B
B
[55,94]
[259,260]
[55,94]
[86]
Bivalirudin (monotherapy)
UFH
Fondaparinux
I
I
III
B
C
B
[255]
Elective PCI
Antiplatelet therapy
Anticoagulation
NSTE-ACS
Antiplatelet therapy
Anticoagulation
Very high-risk of ischaemia e
Medium-to-high-risk of ischaemia e
Low-risk of ischaemia e
[251]
[251]
[250]
[55,60]
[250]
[55,60]
STEMI
Antiplatelet therapy
[246,252]
[248,253]
Anticoagulation
a
[256]
Class of recommendation.
b
Level of evidence.
c
References.
d
Depending on approval and availability. Direct comparison between prasugrel and ticagrelor is not available. Long term follow-up is awaited for both drugs.
e
See Table 12 for definition of ischaemia risk.
f
Primarily if more efficient antiplatelet agents are contraindicated.
ASA = acetylsalicylic acid; DAPT = dual antiplatelet therapy; GPIIb IIIa = glycoprotein IIb IIIa; NSTE-ACS = non-ST-segment elevation acute coronary syndrome;
PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction; UFH = unfractionated heparin.
S36
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
(b) Anticoagulation
Unfractionated heparin (UFH) is currently the standard
anti-thrombotic medication: 70 100 IU/kg i.v. bolus without GPIIb IIIa inhibitors, and 50 70 IU/kg with GPIIb IIIa
inhibitors [55]. The STEEPLE trial has suggested a benefit of
enoxaparin (0.5 or 0.75 mg/kg i.v. bolus) compared with UFH
with reduced bleeding hazard but comparable efficacy [244].
This was at the cost of increased mortality in a lowerdose group, which was terminated early. An association
between mortality and 0.5 mg/kg enoxaparin could not be
demonstrated.
12.2. Non-ST-segment elevation acute
coronary syndrome
High ischaemic risk is associated with ST-segment changes,
elevated troponin, diabetes, and a GRACE score >140. A high
bleeding risk is associated with female sex, age >75 years,
bleeding history, GFR <30 mL/min, and use of femoral access
(Section 7).
(a) Antiplatelet therapy
DAPT includes ASA 150 300 mg per os or 250 ( 500) mg i.v.
bolus, followed by 75 100 mg daily, and clopidogrel 600 mg
loading dose, followed by 75 mg daily, or prasugrel 60 mg
loading dose, followed by 10 mg daily, or ticagrelor 180 mg
loading dose, followed by 90 mg twice daily, depending on
drug availability. A higher clopidogrel maintenance dose for
1 or 2 weeks immediately following stent implantation has
shown some benefit in terms of reduced MACE rates without
significantly increased bleeding [245].
Prasugrel has been tested against the 300 mg loading
dose of clopidogrel, both started in the catheterization
laboratory after diagnostic angiography, in the TRITON
TIMI 38 trial and proved beneficial with respect to
a combined thromboembolic ischaemic outcome [246].
Recurrent cardiovascular events were significantly reduced
in prasugrel-treated patients. Severe bleeding complications
increase with prasugrel use, specifically in patients with a
history of stroke and TIA, in the elderly (75 years), and in
underweight patients (<60 kg). Bleeding was also increased
in prasugrel-treated patients referred for early CABG.
Excluding patients with a higher bleeding risk, prasugrel
offers significant benefit over clopidogrel with respect to
cardiovascular events without increasing severe bleeding.
In diabetic patients presenting with ACS, prasugrel confers
a significant advantage over clopidogrel without increased
bleeding [247]. Prasugrel should be used in patients who
present with stent thrombosis whilst taking clopidogrel.
Ticagrelor, a non-thienopyridine ADP receptor blocker
causing reversible inhibition of platelet function, has been
compared with clopidogrel. The PLATO study confirmed
a significant improvement of combined clinical endpoints
including mortality in favour of ticagrelor [248]. The rate
of severe non-CABG-related bleeding was similar to that of
prasugrel in the TRITON-TIMI 38 trial, while CABG-related
bleeding was lower than for clopidogrel, most probably a
consequence of the faster inactivation of the agent after
stopping intake.
GPIIb IIIa inhibitors should be used in patients with
high ischaemic risk undergoing PCI. The greatest benefit
of GPIIb IIIa inhibitors vs. placebo was demonstrated in
earlier RCTs when ADP receptor blockers were not routinely
used [60]. The usefulness of upstream eptifibatide, with
or without clopidogrel on board, was not confirmed in
EARLY-ACS. The lack of benefit was associated with a higher
bleeding risk [65]. The selective ‘downstream administration’ of abciximab in the catheterization laboratory, in
combination with a 600 mg clopidogrel loading dose, has
been shown to be effective in troponin-positive NSTE-ACS
patients [249] and might therefore be preferred over
upstream use.
(b) Anticoagulation
The golden rule is to avoid crossover especially between
UFH and low molecular weight heparin (LMWH) [60] and
to discontinue antithrombins after PCI except in specific
individual situations (e.g. thrombotic complication).
Management prior to catheterization
Risk stratification in NSTE-ACS patients determines the use
of specific agents and doses.
Patients at very high ischaemic risk (e.g. persistent
angina, haemodynamic instability, refractory arrhythmias)
should immediately be referred to the catheterization
laboratory and receive UFH 60 IU/kg i.v. bolus, followed by
infusion until PCI, combined with DAPT. In patients at high
risk of bleeding, bivalirudin monotherapy with 0.75 mg/kg
bolus followed by 1.75 mg/kg/h can be used.
In medium-to-high ischaemic risk patients (e.g. troponin
positive, recurrent angina, dynamic ST changes) for whom
an invasive strategy is planned within 24 ( 48) h, options for
anticoagulation are:
• In patients <75 years
UFH 60 IU/kg i.v. bolus, then infusion until PCI, controlled
by activated partial thromboplastin time (aPTT)
or
Enoxaparin 1 mg/kg subcutaneous (s.c.) twice daily until
PCI
or
Fondaparinux 2.5 mg daily s.c. until PCI
or
Bivalirudin 0.1 mg/kg i.v. bolus followed by infusion of
0.25 mg/kg/h until PCI
• In patients 75 years
UFH 60 IU/kg i.v. bolus, then infusion (aPTT controlled)
until PCI
or
Enoxaparin 0.75 mg/kg twice daily until PCI
or
Fondaparinux 2.5 mg daily s.c.
or
Bivalirudin 0.1 mg/kg i.v. bolus followed by infusion of
0.25 mg/kg/h until PCI.
In low ischaemic risk patients (troponin negative, no STsegment changes), a primarily conservative strategy is
planned. Anticoagulation is maintained until PCI using
fondaparinux 2.5 mg s.c. daily or enoxaparin 1 mg/kg s.c.
twice daily (0.75 mg in patients 75 years) or UFH 60 IU/kg
i.v. bolus followed by infusion (aPTT controlled).
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Management during catheterization
The golden rule is to continue the initial therapy and
avoid switching between antithrombins (with the exception
of adding UFH to fondaparinux).
UFH. Continue infusion, activated clotting time measurement can be used: target range: 200 250 s with GPIIb IIIa
inhibitors; 250 350 s without GPIIb IIIa inhibitors.
Enoxaparin. Less than 8 h since last s.c. application:
no additional bolus; within 8 12 h of last s.c. application:
add 0.30 mg/kg i.v. bolus; >12 h since last s.c. application:
0.75 mg/kg i.v. bolus.
Bivalirudin. Add an additional i.v. bolus of 0.5 mg/kg and
increase the infusion rate to 1.75 mg/kg/h before PCI.
Fondaparinux. Add UFH 50 100 IU/kg when PCI is
performed.
Fondaparinux, an indirect factor Xa inhibitor, has been
tested against enoxaparin in the OASIS-5 trial [250]. While
the combined ischaemic event rate was similar, severe
bleeding complications were highly significantly reduced
with fondaparinux. This favourable net clinical outcome
with fondaparinux included reduced long-term mortality and
stroke rates. Because of a higher rate of catheter thrombosis
when fondaparinux alone was used, UFH should be added for
patients referred for angiography and PCI.
Bivalirudin, a direct antithrombin, alone or in combination
with GPIIb IIIa inhibition, was compared with UFH/
enoxaparin + GPIIb IIIa inhibition. Bivalirudin monotherapy
was superior to either regimen with respect to reduced
bleeding, without increased ischaemic events [251].
12.3. ST-segment elevation myocardial
infarction
(a) Antiplatelet therapy
DAPT consists of ASA 150 300 mg per os or 250 ( 500) mg
bolus i.v., followed by 75 100 mg daily, and prasugrel 60 mg
loading dose, followed by 10 mg daily, or ticagrelor 180 mg
loading dose, followed by 90 mg twice daily, depending
on drug availability [94]. Clopidogrel 600 mg loading dose,
followed by 75 mg daily, should be used primarily if the
more effective ADP receptor blockers are contraindicated
or unavailable.
Increasing the maintenance dose of clopidogrel for
1 2 weeks might be effective in STEMI patients, as shown
in NSTE-ACS. Prasugrel is superior to clopidogrel (300 mg
loading dose, 75 mg maintenance dose) in reducing combined
ischaemic endpoints and stent thrombosis in STEMI patients
without increasing the risk of severe bleeding [252].
A predefined subgroup analysis has demonstrated that
STEMI or NSTE-ACS patients referred for PCI significantly
benefit from ticagrelor, vs. clopidogrel, with similar bleeding
rates [253].
Most studies of GPIIb IIIa inhibitors in STEMI have
evaluated abciximab (0.25 mg/kg i.v. bolus followed by
infusion of 0.125 mg/kg/min up to a maximum of 10 mg/min
for 12 h). Findings are mixed regarding the effectiveness of
facilitation (early administration) with GPIIb IIIa inhibitors
before catheterization. While the only available RCT [86]
showed no benefit, registries, meta-analyses, and post hoc
analyses of APEX-AMI [254] show positive results. The
controversial literature data, the negative outcome of the
S37
only prospective RCT [86], and the beneficial effects of
faster acting and more efficacious ADP receptor blockers
in primary PCI do not support pre-hospital or precatheterization use of GPIIb IIIa inhibitors.
(b) Anticoagulation
Options for anticoagulation include UFH 60 IU/kg i.v. bolus
with GPIIb IIIa inhibitor or UFH 100 IU/kg i.v. bolus without
GPIIb IIIa inhibitor, or bivalirudin 0.75 mg/kg bolus followed
by 1.75 mg/kg/h. Antithrombins can be stopped after PCI for
STEMI with few exceptions (LV aneurysm and/or thrombus,
AF, prolonged bed rest, deferred sheath removal).
A recent study suggested bivalirudin monotherapy as
an alternative to UFH plus a GPIIb IIIa inhibitor [255].
Significantly lower severe bleeding rates led to a beneficial
net clinical outcome indicating that bivalirudin may be
preferred in STEMI patients at high risk of bleeding. Oneyear outcome of the HORIZONS RCT confirmed the beneficial
action of bivalirudin monotherapy vs. UFH and a GPIIb IIIa
inhibitor. Uncertainty remains in the early phase of primary
PCI, when thrombotic complications seem to be higher
with bivalirudin monotherapy. However, this had no effect
on long-term clinical outcome, probably because acute inhospital stent thrombosis can be promptly addressed, unlike
late out-of-hospital stent thrombosis.
Fondaparinux was inferior to UFH in the setting of primary
PCI in patients with STEMI (OASIS-6 trial) [256].
12.4. Points of interest and special conditions
(a) Bleeding complications
Bleeding contributes to worse outcome and can be
prevented by implementing the following measures:
• formally assess and document bleeding risk in every
patient;
• avoid crossover between UFH and LMWH;
• adjust antithrombotic therapy doses based on weight and
renal function (Table 37);
• use radial access in patients at high risk of bleeding;
• stop anticoagulation after PCI unless a specific indication
exists;
• adopt selective downstream use of GPIIb IIIa inhibitors, as
required in the catheterization laboratory, in preference
to unselective upstream use.
(b) Recommended duration of dual antiplatelet
therapy
After percutaneous coronary intervention
• 1 month after BMS implantation in stable angina [55,60,
94];
• 6 12 months after DES implantation in all patients [60,94];
• 1 year in all patients after ACS, irrespective of
revascularization strategy.
Data suggest that certain patient populations (e.g. high
risk for thromboembolic events, patients after SES or PES
implantation), may benefit from prolonged DAPT beyond
1 year. The downside of this strategy is the increased rate
of severe bleeding complications over time. Recent data
suggest that DAPT for 6 months might be sufficient because
late and very late stent thrombosis correlate poorly with
discontinuation of DAPT.
S38
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 37
Recommendations of antithrombotic drug use in chronic kidney disease
Antiplatelet therapy
ASA
Clopidogrel
Prasugrel a
Ticagrelor a
GPIIb IIIa antagonists
Abciximab
Tirofiban
Eptifibatide
Anticoagulation
UFH
Enoxaparin (and
other LMWHs)
Fondaparinux
Bivalirudin
No specific recommendations.
No information in patients with renal dysfunction.
No dosage adjustment is necessary for patients
with renal impairment, including patients with
end stage renal disease.
No dose reduction required in patients with
GFR <60 mL/min/1.73 m2 .
No specific recommendations for the use or dose
adjustment in the case of renal failure.
Dose adaptation required in patients with
renal failure: 50% of the dose with GFR of
<30 mL/min/1.73 m2 .
Dose adaptation in moderate renal impairment
(GFR <60 mL/min/1.73 m2 ). Contraindicated in
severe renal dysfunction.
Dose reduction necessary based on frequent aPTT
measurements to control therapeutic range.
In case of severe renal failure (GFR <30 mL/min/
1.73 m2 ) either to be avoided or
50% dose reduction and control of therapeutic
levels by factor Xa-activity measurements.
In patients with reduced GFR (range 30 60
mL/min/1.73 m2 ) dose reduction to 75% of the
recommended full dose.
Contraindicated in severe renal failure
(<30 mL/min/1.73 m2 ); drug of choice
in patients with reduced renal function
(GFR 30 60 mL/min/1.73 m2 ) due to lower risk of
bleeding complications compared with enoxaparin.
Consider reduction of infusion rate to 1.0 mg/kg/h
in patients with severe renal dysfunction; consider
use in patients with NSTE-ACS and reduced renal
function (GFR 30 60 mL/min/1.73 m2 ) undergoing
angiography ± PCI due to lower bleeding risk
compared with UFH + GPIIb IIIa antagonists.
a
Depending on approval and availability.
aPTT = activated partial thromboplastin time; ASA = acetylsalicylic acid;
GFR = glomerular filtration rate; GPIIb IIIa = glycoprotein IIb IIIa; LMWHs =
low molecular weight heparins; NSTE-ACS = non-ST-segment elevation acute
coronary syndrome; PCI = percutaneous coronary intervention; UFH =
unfractionated heparin.
After coronary artery bypass grafting
Indications for DAPT and treatment duration depend
primarily on the clinical indication (stable CAD, NSTEACS, STEMI), irrespective of the mode of revascularization.
Secondary prevention demands lifelong antiplatelet therapy
with 75 325 mg ASA daily (Section 13).
Antiplatelet agents also promote long-term graft patency,
especially SVG. In cases of aspirin intolerance, clopidogrel
should be used. There are no RCTs comparing the efficacy
of clopidogrel or clopidogrel plus aspirin vs. aspirin alone on
long-term graft patency.
(c) Triple antithrombotic therapy
Triple therapy consisting of ASA, clopidogrel (or prasugrel),
and a vitamin K antagonist should only be given if a
compelling indication exists, i.e. paroxysmal, persistent, or
permanent AF with CHADS2 score 2, mechanical valves,
recent or recurrent history of deep venous thrombosis,
or pulmonary embolism. Triple therapy should only be
prescribed for the shortest necessary duration with frequent
INR measurement (target INR 2 2.5) [257]. In patients with
a compelling indication for long-term anticoagulation, BMS
implantation or stand-alone balloon angioplasty or CABG
should be preferred over DES to restrict the duration of triple
therapy to 1 month.
(d) Drug interactions and genetic testing:
a clopidogrel-related topic
Statins interact with clopidogrel metabolism through
CYP3A4, a drug interaction that has little if any clinical
relevance.
Proton pump inhibitors are frequently administered in
combination with DAPT to reduce the risk of gastrointestinal
bleeding. European and US regulatory agencies have
issued warnings regarding diminished clopidogrel action
when combined with proton pump inhibitors (especially
omeprazole and esomeprazole). Post hoc analyses of CREDO
and TRITON-TIMI 38 RCTs [258] did not show increased
thromboembolic events. Accordingly, proton pump inhibitors
should not be withheld when indicated.
The presence of the CYP2C19 loss-of-function allele seems
to be associated with an increased risk of atherothrombotic
complications in clopidogrel-treated patients. This allele
does not influence the action of prasugrel on platelet
function.
(e) Renal dysfunction
The extent of CKD is strongly related to the risk of
adverse in-hospital outcomes. As many antithrombotic drugs
are metabolized or excreted by the kidneys, an accurate
assessment of renal function is required for proper dose
adjustment. In general, most antithrombotic agents are
contraindicated or need dose reduction in CKD patients
(Table 37). In patients referred for acute PCI, the first dose
of an antithrombotic drug usually does not add to the risk
of bleeding in cases of CKD. Repeated infusion or intake
might lead to drug accumulation and increase bleeding risk.
Accordingly, patients with CKD should receive the same firstline treatment as any other patient, in the absence of
contraindications. Thereafter, dose adaptation is mandatory
with respect to kidney function and specific antithrombotic
agents may be preferred (Table 37).
(f) Surgery in patients on dual antiplatelet therapy
Management of patients on DAPT who are referred for
surgical procedures depends on the level of emergency and
the thrombotic and bleeding risk of the individual patient
(Figure 3). Most surgical procedures can be performed on
DAPT or at least on ASA alone with acceptable rate of bleeding. A multidisciplinary approach is required (cardiologist,
anaesthesiologist, haematologist, and surgeon) to determine
the patient’s risk and to choose the best strategy.
In surgical procedures with high to very high bleeding
risk, including CABG, it is recommended that clopidogrel
be stopped 5 days before surgery and ASA continued.
Prasugrel should be stopped 7 days before surgery based on
its prolonged and more effective action than clopidogrel.
In the PLATO trial, ticagrelor was discontinued 48 72 h
before surgery. DAPT should be resumed as soon as possible
including a loading dose for clopidogrel and prasugrel (if
possible <24 h after operation).
In very high risk patients in whom cessation of antiplatelet
therapy before surgery is judged to be too hazardous (e.g.
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Cardiac/non-cardiac surgery
Emergent
Semi-elective
and urgent
Proceed to
surgery
‘Case-by-case’
decision
Risk of
thrombosis
Elective
Wait until completion
of the mandatory
dual antiplatelet
regimen
Continue
ASA + clopidogrel
Continue ASA
stop clopidogrel
Risk of
bleeding
Stop ASA
stop clopidogrel
ASA = acetylsalicylic acid.
Fig. 3
Algorithm for pre-operative management of patients considered
for/undergoing surgery treated with dual antiplatelet therapy.
within the first weeks after stent implantation), it has
been suggested that a patient be switched from clopidogrel
5 days before surgery to a reversible antiplatelet agent with
a short half-life, e.g. the GPIIb IIIa inhibitor tirofiban or
eptifibatide, stopping the infusion 4 h before surgery. The
substitution of DAPT with LMWH or UFH is ineffective.
In surgical procedures with low to moderate bleeding risk,
surgeons should be encouraged to operate on DAPT.
(g) Antiplatelet therapy monitoring
Residual platelet activity on DAPT can be measured in
various ways, including point of care bedside tests. There
is no consensus on the system to be used, on the definition
of poor response, and on the course of action. Many studies
have shown associations between unwanted effects and a
lower response to DAPT; however, there is no evidence from
RCTs that tailored antiplatelet therapy improves outcome.
Monitoring of antiplatelet response by platelet function
assays is currently used for clinical research, but not in daily
clinical practice.
(h) Patients with ASA hypersensitivity
In patients with ASA hypersensitivity and in whom ASA
therapy is mandatory, a rapid desensitization procedure may
be performed.
(i) Heparin-induced thrombocytopenia
In patients with a history of heparin-induced thrombocytopenia, neither UFH nor LMWH should be used because of
cross-reactivity. In this case, bivalirudin is the best option
and other possible options are fondaparinux, argatroban,
hirudin, lepirudin, and danaparoid.
13. Secondary prevention
13.1. Background and rationale
Myocardial revascularization must be accompanied by
adequate secondary prevention strategies: OMT, risk factor
S39
modification, and permanent lifestyle changes [12,60,
94,158,261].
Cardiac rehabilitation and secondary prevention are an
essential part of long-term management after revascularization because such measures reduce future morbidity and
mortality, in a cost-effective way [60,94,158,262].
13.2. Modalities
Patients require counselling to adopt a healthy lifestyle
and encourage adherence to their medication plan. The
role of the interventional cardiologist and cardiac surgeon
is to recommend cardiac rehabilitation and secondary
prevention to all revascularized patients. Therapy should
be initiated during hospitalization when patients are
highly motivated. Adherence to lifestyle and risk factor
modification requires individualized behavioural education
and can be implemented during exercise-based cardiac
rehabilitation. Education should be interactive with full
participation of patient care-givers, providing an explanation for each intervention while early mobilization and
physical conditioning programme should vary according to
individual clinical status (Table 38) [261,263]. Adherence to
the prescribed recommendations and the achievement of
the planned goals should be evaluated during regular clinical
evaluation (at 6-month intervals).
For functional evaluation and exercise training prescription, symptom-limited exercise testing can be safely
performed 7 14 days after primary PCI for STEMI and as
soon as 24 h after elective PCI. Algorithms for prescription
of functional evaluation at the onset of rehabilitation or
exercise programmes after PCI and CABG are proposed in
Figures 4 and 5: submaximal exercise evaluations and 6-min
walk tests represent useful alternatives to symptom-limited
stress testing, which should be considered as the first choice
approach [262].
Echocardiography should be performed after CABG and
can be considered after PCI to ascertain global LV function
and regional wall motion. During physical training, exercise
intensity should be set at 70 85% of the peak heart rate.
In the case of symptomatic exercise-induced ischaemia, the
level of exercise intensity can be set either at 70 85% of the
ischaemic heart rate or just below the anginal threshold.
In asymptomatic exercise-induced ischaemia, exercise to
70 85% of the heart rate at the onset of ischaemia (defined
as 1 mm of ST depression) has been proposed.
Table 39 lists the pharmacological components of OMT.
For practical purposes the mnemonic ‘ABCDE’ approach
has been proposed: ‘A’ for antiplatelet therapy (Table 36),
anticoagulation, angiotensin-converting enzyme inhibition,
or angiotensin receptor blockade; ‘B’ for b-blockade and
blood pressure control; ‘C’ for cholesterol treatment and
cigarette smoking cessation; ‘D’ for diabetes management
and diet; and ‘E’ for exercise.
13.3. Settings
Cardiac rehabilitation and secondary prevention programmes are implemented in or out of hospital, according
to the clinical status and the local facilities. A structured
in-hospital (residential) cardiac rehabilitation programme,
S40
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 38
Long-term lifestyle and risk factor management after myocardial revascularization
Long-term management is based on risk stratification that should include:
• full clinical and physical evaluation
• ECG
• laboratory testing
• HbA1c
• physical activity level by history and exercise testing
• echocardiogram prior to and after CABG.
Echocardiography should be considered pre- or post-PCI.
• Counselling on physical activity and exercise training should include a minimum of 30 60 min/day of moderately intense
aerobic activity.
• Medically supervised programmes are advisable for high-risk patients (e.g. recent revascularization, heart failure).
Resistance training 2 days/week may be considered
• Diet and weight control management should aim at BMI <25 kg/m2 and waist circumferences <94 cm in men and
<80 cm in women.
• It is recommended to assess BMI and/or waist circumferences on each visit and consistently encourage weight
maintenance/reduction.
• The initial goal of weight-loss therapy is the reduction of body weight by ~10% from baseline.
• Healthy food choices are recommended.
• Dietary therapy and lifestyle changes are recommended.
• It is recommended to reach LDL-cholesterol <100 mg/dL (2.5 mmol/L).
• In high-risk patients, it is recommended to reach LDL-cholesterol <70 mg/dL (2.0 mmol/L).
Increased consumption of omega-3 fatty acids in the form of fish oil may be considered.
• It is recommended to implement lifestyle changes and pharmacotherapy in order to achieve blood pressure <130/80 mmHg.
• b-Blockers and/or ACE inhibitors are indicated as first-line therapy.
It is recommended to assess, at each visit, smoking status, to insist on smoking cessation, and to advise avoiding passive
smoking.
In patients with diabetes, the following is recommended:
• Lifestyle changes and pharmacotherapy to achieve HbA1c <6.5%.
• Vigorous modification of other risk factors.
• Coordination of diabetic care with a specialized physician.
Screening for psychological distress is indicated.
Annual influenza vaccination is indicated.
Class a
Level b
Ref. c
I
I
I
I
I
I
IIa
I
C
B
B
A
B
C
C
A
I
IIb
I
B
C
B
[12]
I
B
[12,266]
I
I
I
I
I
IIb
I
I
I
B
B
B
A
B
B
A
A
B
[12]
[94]
[12]
[94]
[110]
[261]
[12,261]
[12]
[12,94]
I
I
I
I
I
B
B
C
C
B
[12,94]
[12]
[12]
[12]
[264]
[12,265]
[12,94]
[263]
[12,94]
a
Class of recommendation.
b
Level of evidence.
c
References.
ACE = angiotensin-converting enzyme; BMI = body mass index; CABG = coronary artery bypass grafting; ECG = electrocardiogram; HbA1c = glycated haemoglobin;
LDL = low density lipoprotein; PCI = percutaneous coronary intervention.
either in a hospital or in a dedicated centre, is
ideal for high-risk patients, who may have persistent
clinical, haemodynamic, or arrhythmic instability, or severe
complications or comorbidities.
After uncomplicated PCI or CABG procedures, physical
activity counselling can start the following day, and such
patients can walk on the flat and up the stairs within a few
days. After a revascularization procedure in patients with
significant myocardial damage, physical rehabilitation should
start after clinical stabilization.
The following general criteria should be considered in
planning an exercise testing modality for exercise prescription: safety, i.e. stability of clinical, haemodynamic, and
rhythmic parameters, ischaemic and angina threshold (in the
case of incomplete revascularization), degree of LV impairment; associated factors (i.e. sedentary habits, orthopaedic
limitations, occupational and recreational needs).
14. Strategies for follow-up
Although the need to detect restenosis has diminished in the
DES era, a sizeable proportion of patients are still treated
with BMS or balloon angioplasty with high recurrence rates.
Likewise, the durability of CABG results has increased with
the use of arterial grafts and ischaemia stems mainly from
SVG attrition and/or progression of CAD in native vessels.
Follow-up strategies should focus not only on the
detection of restenosis or graft occlusion, but also on the
assessment of patients’ functional status and symptoms, as
well as on secondary prevention. A baseline assessment of
physical capacity is needed when entering a rehabilitation
programme after revascularization [265].
Physical examination, resting ECG, and routine laboratory
testing should be performed within 7 days after PCI.
Special attention should be given to puncture site healing,
haemodynamics, and possible anaemia or CIN. For ACS
patients, plasma lipids should be re-evaluated 4 6 weeks
after an acute event and/or initiation of lipid-lowering
therapy to evaluate whether target levels have been
achieved and to screen for liver dysfunction; the second
plasma lipid control should be scheduled at 3 months [263].
For patients with stable CAD, there is a need to
evaluate muscle symptoms and enzymes initially after
statin introduction, then to evaluate muscle symptoms
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
S41
Patient after PCI
Postpone
exercise
test
Yes
Clinical, haemodynamic, and rhythm instability
No
Incomplete coronary revascularization and/or
LVEF <40%
Yes
No
Physical activity before PCI:
sedentary
Yes
Physical activity before PCI:
sedentary
No
6 min
walking test
Yes
6 min
submaximal
steady-state
exercise test *
No
Submaximal
incremental
exercise test §
Symptom
-limited
exercise test
Fig. 4. Algorithm for prescription of functional evaluation at the onset of rehabilitation or exercise programme after percutaneous coronary intervention. The
following general criteria should be considered in planning an exercise testing modality for exercise prescription: safety, i.e. stability of clinical, haemodynamic
and rhythmic parameters, ischaemic and angina threshold (in the case of incomplete revascularization), degree of left ventricular ejection fraction impairment,
associated factors (i.e. sedentary habits, orthopaedic limitations, occupational and recreational needs). *Upper limit for terminating submaximal 6-min singlestage (steady-state) exercise testing: rate of perceived exertion (Borg scale) 11 13/20 or maximal heart rate = heart rate at standing rest + 20 30 beats/min.
§
Upper limit for terminating submaximal incremental testing: maximal heart rate = 70% heart rate reserve or 85% of age-predicted maximal heart rate. LVEF = left
ventricular ejection fraction; PCI = percutaneous coronary intervention.
Patient after CABG
Yes
Postpone
exercise
test
Clinical, haemodynamic, and rhythm instability
No
Yes
Reversible Hb <10 g/dL and/or instability of the
sternum and/or muscular/skeletal discomfort
No
Incomplete coronary revascularization and/or
LVEF <40%, and/or deconditioning
Yes
Physical activity before
surgery: sedentary
Yes
6 min
walking test
No
6 min
submaximal
steady-state
exercise test*
No
Physical activity before
surgery: sedentary
Yes
Submaximal
incremental
exercise test§
No
Symptom
-limited
exercise test
Fig. 5. Algorithm for prescription of functional evaluation at the onset of rehabilitation or exercise programme after coronary artery bypass grafting. The
following general criteria should be considered in planning exercise testing modality for exercise prescription: safety; comorbidities, i.e. haemoglobin values,
musculoskeletal discomfort, healing issues at the incision sites; associated factors, i.e. deconditioning due to prolonged hospitalization, sedentary habits,
orthopaedic limitations, occupational and recreational needs (see also legend to Figure 4). CABG = coronary artery bypass grafting; Hb = haemoglobin; LVEF = left
ventricular ejection fraction.
S42
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
to assess coronary flow non-invasively, but larger studies are
needed to confirm the accuracy of this technique.
Table 39
Long-term medical therapy after myocardial revascularization
• ACE inhibitors should be started and
continued indefinitely in all patients with
LVEF 40% and for those with hypertension,
diabetes, or CKD, unless contraindicated.
• ACE inhibitors should be considered in all
patients, unless contraindicated.
• Angiotensin receptor blockers are
indicated in patients who are intolerant
of ACE inhibitors and have HF or MI with
LVEF 40%.
• Angiotensin receptor blockers should be
considered in all ACE-inhibitor intolerant
patients.
• It is indicated to start and continue
b-blocker therapy in all patients after
MI or ACS or LV dysfunction, unless
contraindicated.
• High-dose lipid lowering drugs are indicated
in all patients regardless of lipid levels,
unless contraindicated.
• Fibrates and omega-3 fatty acids (1 g/day)
should be considered in combination with
statins and in patients intolerant of statins.
• Niacin may be considered to increase
HDL cholesterol.
Class a
Level b
Ref. c
I
A
[12]
IIa
A
[94]
I
A
[12]
IIa
A
[94]
I
A
[12]
I
A
[94,110,
267]
IIa
B
[12,261]
IIb
B
[268]
a
Class of recommendation.
b
Level of evidence.
c
References.
ACE = angiotensin-converting enzyme; ACS = acute coronary syndrome;
CKD = chronic kidney disease; HDL = high density lipoprotein; HF = heart
failure; LV = left ventricle; LVEF = left ventricular ejection fraction;
MI = myocardial infarction.
Imaging stent or graft patency
CT angiography can detect occluded and stenosed grafts
with very high diagnostic accuracy [18,19]. However, clinical
assessment should not be restricted to graft patency but
should include evaluation of the native coronary arteries.
This will often be difficult because of advanced CAD
and pronounced coronary calcification. Furthermore, it is
acknowledged that anatomical imaging by CT angiography
does not assess ischaemia, which remains essential for
therapeutic decisions. CT angiography can detect in-stent
restenosis, depending on stent type and diameter, yet the
aforementioned limitations equally apply. Patients who have
undergone unprotected LM PCI may be scheduled for routine
control CT or invasive angiography within 3 12 months.
Recommendations for follow-up strategies in asymptomatic and symptomatic patients are summarized in
Tables 40 and 41. These recommendations assume that
patients comply with appropriate lifestyle changes and
receive OMT [12,14,43,270].
Table 40
Strategies for follow-up and management in asymptomatic patients after
myocardial revascularization
Stress imaging (stress echo or MPS) should be
used rather than stress ECG.
• With low-risk findings (+) at stress testing,
the reinforcement of OMT and lifestyle
changes should be considered.
• With high- to intermediate-risk findings (++)
at stress testing, coronary angiography
should be considered.
Early imaging testing should be considered in
specific patient subsets. d
Routine stress testing may be considered
2 years after PCI and >5 years after CABG.
at each follow-up visit, and to evaluate enzymes if the
patient presents muscle soreness, tenderness, or pain. Liver
enzymes should be evaluated initially, 8 12 weeks after
statin initiation, after dose increase, then annually or more
frequently if indicated.
a
Stress testing
Previously published guidelines [269] and several authors
warn against routine testing of asymptomatic patients.
Others argue that all patients should undergo stress testing
following revascularization, given the adverse outcome
associated with silent ischaemia. Early stress testing in order
to verify that culprit lesions have been successfully treated
may be recommended after incomplete or suboptimal
revascularization as well as in other specific patient subsets
(Table 40). Stress ECG should preferably be combined with
functional imaging, due to low sensitivity and specificity of
stress ECG alone in this subset [269], its inability to localize
ischaemia, and to assess improvement in regional wall motion of revascularized segments. Exercise is considered the
most appropriate stressor, but in patients unable to exercise,
pharmacologic stressors
dipyridamole, dobutamine, and
adenosine are recommended. The inability to perform an
exercise stress test, by itself, indicates a worse prognosis.
The choice between imaging modalities is based on similar
criteria to those used before intervention (Section 5). With
repeated testing, radiation burden should be considered
as part of the test selection. Estimation of coronary flow
using transthoracic Doppler echocardiography may be used
Class a
Level b
Ref. c
I
A
[12,269]
IIa
C
IIa
C
IIb
C
Class of recommendation.
Level of evidence.
References.
d
Specific patient subsets indicated for early stress testing with imaging:
• predischarge, or early post-discharge imaging stress test in STEMI patients
treated with primary PCI or emergency CABG;
• patients with safety critical professions (e.g. pilots, drivers, divers) and
competitive athletes;
• users of 5-phosphodiesterase inhibitors;
• patients who would like to be engaged in recreational activities for which
high oxygen consumption is required;
• patients resuscitated from sudden death;
• patients with incomplete or suboptimal revascularization, even if
asymptomatic;
• patients with a complicated course during revascularization (perioperative MI, extensive dissection during PCI, endarterectomy during CABG, etc.);
• patients with diabetes (especially those requiring insulin);
• patients with MVD and residual intermediate lesions, or with silent
ischaemia.
(+) Low-risk findings at stress imaging are ischaemia at high workload, late
onset ischaemia, single zone of low grade wall motion abnormality or small
reversible perfusion defect, or no evidence of ischaemia.
(++) Intermediate- and high-risk findings at stress imaging are ischaemia at
low workload, early onset ischaemia, multiple zones of high grade wall motion
abnormality, or reversible perfusion defect.
CABG = coronary artery bypass grafting; ECG = electrocardiogram; MI = myocardial infarction; MPS = myocardial perfusion stress; MVD = multivessel disease;
OMT = optimal medical therapy; PCI = percutaneous coronary intervention;
STEMI = ST-segment elevation myocardial infarction.
b
c
ESC/EACTS Task Force on Myocardial Revascularization / European Journal of Cardio-thoracic Surgery 38 (2010) S1 S52
Table 41
Strategies for follow-up and management in symptomatic patients after
myocardial revascularization
Stress imaging (stress echo or MPS) should be
used rather than stress ECG.
It is recommended to reinforce OMT and
life style changes in patients with low-risk
findings (+) at stress testing.
With intermediate- to high-risk findings (++)
at stress testing, coronary angiography is
recommended.
Emergent coronary angiography is
recommended in patients with STEMI.
Early invasive strategy is indicated in high-risk
NSTE-ACS patients.
Elective coronary angiography is indicated in
low-risk NSTE-ACS patients.
Class a
Level b
Ref. c
I
A
[12,269]
I
B
[14,43,
270]
I
C
I
A
[94]
I
A
[60]
I
C
a
Class of recommendation.
Level of evidence.
c
References.
(+) Low-risk findings at stress imaging are ischaemia at high workload, late
onset ischaemia, single zone of low grade wall motion abnormality or small
reversible perfusion defect, or no evidence of ischaemia.
(++) Intermediate- and high-risk findings at stress imaging are ischaemia at
low workload, early onset ischaemia, multiple zones of high grade wall motion
abnormality or reversible perfusion defect.
ECG = electrocardiogram; MPS = myocardial perfusion stress; NSTE-ACS = nonST-segment elevation acute coronary syndrome; OMT = optimal medical
therapy; STEMI = ST-segment elevation myocardial infarction.
b
Most of the statements in these clinical practice guidelines
are supported by published evidence. Only a minority of the
publications that support the written text were listed in the
following abridged reference list of the guidelines. Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.ejcts.2010.08.019 and
also at www.eacts.org.
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