ACCF/AHA/SCAI Practice Guideline 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions WRITING COMMITTEE MEMBERS* Glenn N. Levine, MD, FACC, FAHA, Chair ; Eric R. Bates, MD, FACC, FAHA, Vice Chair* ; James C. Blankenship, MD, FACC, FSCAI, Vice Chair* ; Steven R. Bailey, MD, FACC, FSCAI* ; John A. Bittl, MD, FACC ; Bojan Cercek, MD, FACC, FAHA ; Charles E. Chambers, MD, FACC, FSCAI ; Stephen G. Ellis, MD, FACC* ; Robert A. Guyton, MD, FACC* ; Steven M. Hollenberg, MD, FACC* ; Umesh N. Khot, MD, FACC* ; Richard A. Lange, MD, FACC, FAHA ; Laura Mauri, MD, MSC, FACC, FSCAI* ; Roxana Mehran, MD, FACC, FAHA, FSCAI* ; Issam D. Moussa, MD, FACC, FAHA, FSCAI ; Debabrata Mukherjee, MD, FACC, FSCAI ; Brahmajee K. Nallamothu, MD, FACC ; Henry H. Ting, MD, FACC, FAHA ACCF/AHA TASK FORCE MEMBERS Alice K. Jacobs, MD, FACC, FAHA, Chair; Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect; Nancy Albert, PhD, CCNS, CCRN, FAHA; Mark A. Creager, MD, FACC, FAHA; Steven M. Ettinger, MD, FACC; Robert A. Guyton, MD, FACC; Jonathan L. Halperin, MD, FACC, FAHA; Judith S. Hochman, MD, FACC, FAHA; Frederick G. Kushner, MD, FACC, FAHA; E. Magnus Ohman, MD, FACC; William Stevenson, MD, FACC, FAHA; Clyde W. Yancy, MD, FACC, FAHA *Writing committee members are required to recuse themselves from voting on sections where their specific relationship with industry and other entities may apply; see Appendix 1 for recusal information. ACCF/AHA Representative. Society for Cardiovascular Angiography and Interventions Representative. Joint Revascularization Section Author. ||ACCF/AHA Task Force on Practice Guidelines Liaison. ACCF/AHA Task Force on Performance Measures Liaison. This document was approved by the American College of Cardiology Foundation Board of Trustees and the American Heart Association Science Advisory and Coordinating Committee in July 2011, and the Society for Cardiovascular Angiography and Interventions in August 2011. The American Heart Association requests that this document be cited as follows: Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124:e574 e651. This article has been copublished in the Journal of the American College of Cardiology and Catherization and Cardiovascular Interventions. Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.cardiosource.org) and the American Heart Association (my.americanheart.org). A copy of the document is available at http://my.americanheart.org/statements by selecting either the By Topic link or the By Publication Date link. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com. Expert peer review of AHA Scientific Statements is conducted at the AHA National Center. For more on AHA statements and guidelines development, visit http://my.americanheart.org/statements and select the Policies and Development link. Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/Copyright- Permission-Guidelines_UCM_300404_Article.jsp. A link to the Copyright Permissions Request Form appears on the right side of the page. 2011 by the American College of Cardiology Foundation and the American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIR.0b013e31823ba622 Table of Contents Preamble e576 1. Introduction e578 1.1. Methodology and Evidence Review e578 1.2. Organization of the Writing Committee e579 1.3. Document Review and Approval e579 1.4. PCI Guidelines: History and Evolution e579 2. CAD Revascularization e580 2.1. Heart Team Approach to Revascularization Decisions: Recommendations e580 2.2. Revascularization to Improve Survival: Recommendations e582 2.3. Revascularization to Improve Symptoms: Recommendations e583 2.4. CABG Versus Contemporaneous Medical Therapy e583 2.5. PCI Versus Medical Therapy e584 2.6. CABG Versus PCI e584 2.6.1. CABG Versus Balloon Angioplasty or BMS e584 2.6.2. CABG Versus DES e585 2.7. Left Main CAD e585 2.7.1. CABG or PCI Versus Medical Therapy for Left Main CAD e585 2.7.2. Studies Comparing PCI Versus CABG for Left Main CAD e586 2.7.3. Revascularization Considerations for Left Main CAD e586 2.8. Proximal LAD Artery Disease e587 2.9. Clinical Factors That May Influence the Choice of Revascularization e587 2.9.1. Diabetes Mellitus e587 2.9.2. Chronic Kidney Disease e587 2.9.3. Completeness of Revascularization e587 2.9.4. LV Systolic Dysfunction e588 2.9.5. Previous CABG e588 2.9.6. Unstable Angina/Non ST-Elevation Myocardial Infarction e588 2.9.7. DAPT Compliance and Stent Thrombosis: Recommendation e588 2.10. TMR as an Adjunct to CABG e588 2.11. Hybrid Coronary Revascularization: Recommendations e589 3. PCI Outcomes e589 3.1. Definitions of PCI Success e589 3.1.1. Angiographic Success e589 3.1.2. Procedural Success e589 3.1.3. Clinical Success e589 3.2. Predictors of Clinical Outcome After PCI e590 3.3. PCI Complications e590 4. Preprocedural Considerations e591 4.1. Cardiac Catheterization Laboratory Requirements e591 4.1.1. Equipment e591 4.1.2. Staffing e591 4.1.3. Time-Out Procedures e592 4.2. Ethical Aspects e592 4.2.1. Informed Consent e592 4.2.2. Potential Conflicts of Interest e592 4.3. Radiation Safety: Recommendation e592 4.4. Contrast-Induced AKI: Recommendations e593 4.5. Anaphylactoid Reactions: Recommendations e594 4.6. Statin Treatment: Recommendation e594 4.7. Bleeding Risk: Recommendation e594 4.8. PCI in Hospitals Without On-Site Surgical Backup: Recommendations e594 5. Procedural Considerations e595 5.1. Vascular Access: Recommendation e595 5.2. PCI in Specific Clinical Situations e596 5.2.1. UA/NSTEMI: Recommendations e596 5.2.2. ST-Elevation Myocardial Infarction e597 5.2.2.1. Coronary Angiography Strategies in STEMI: Recommendations e597 5.2.2.2. Primary PCI of the Infarct Artery: Recommendations e598 5.2.2.3. Delayed or Elective PCI in Patients With STEMI: Recommendations e599 5.2.3. Cardiogenic Shock: Recommendations e600 5.2.3.1. Procedural Considerations for Cardiogenic Shock e600 5.2.4. Revascularization Before Noncardiac Surgery: Recommendations e600 5.3. Coronary Stents: Recommendations e601 5.4. Adjunctive Diagnostic Devices e602 5.4.1. FFR: Recommendation e602 5.4.2. IVUS: Recommendations e602 5.4.3. Optical Coherence Tomography e603 5.5. Adjunctive Therapeutic Devices e603 5.5.1. Coronary Atherectomy: Recommendations e603 5.5.2. Thrombectomy: Recommendation e603 5.5.3. Laser Angioplasty: Recommendations e603 5.5.4. Cutting Balloon Angioplasty: Recommendations e603 5.5.5. Embolic Protection Devices: Recommendation e604 5.6. Percutaneous Hemodynamic Support Devices: Recommendation e604 5.7. Interventional Pharmacotherapy e604 5.7.1. Procedural Sedation e604 5.7.2. Oral Antiplatelet Therapy: Recommendations e605 Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e575 5.7.3. IV Antiplatelet Therapy: Recommendations e606 5.7.4. Anticoagulant Therapy e607 5.7.4.1. Use of Parenteral Anticoagulants During PCI: Recommendation e607 5.7.4.2. UFH: Recommendation e607 Recommendations e608 5.7.4.4. Bivalirudin and Argatroban: Recommendations e608 Recommendation e609 5.7.5. No-Reflow Pharmacological Therapies: Recommendation e610 5.8. PCI in Specific Anatomic Situations e610 5.8.1. CTOs: Recommendation e610 5.8.2. SVGs: Recommendations e610 5.8.3. Bifurcation Lesions: Recommendations e611 5.8.4. Aorto-Ostial Stenoses: Recommendations e611 5.8.5. Calcified Lesions: Recommendation e611 5.9. PCI in Specific Patient Populations e612 5.9.1. Elderly e612 5.9.2. Diabetes e612 5.9.3. Women e612 5.9.4. CKD: Recommendation e612 5.9.5. Cardiac Allografts e612 5.10. Periprocedural MI Assessment: Recommendations e613 5.11. Vascular Closure Devices: Recommendations e613 6. Postprocedural Considerations e613 6.1. Postprocedural Antiplatelet Therapy: Recommendations e613 6.1.1. PPIs and Antiplatelet Therapy: Recommendations e615 6.1.2. Clopidogrel Genetic Testing: Recommendations e615 6.1.3. Platelet Function Testing: Recommendations e616 6.2. Stent Thrombosis e616 6.3. Restenosis: Recommendations e616 6.3.1. Background and Incidence e616 6.3.2. Restenosis After Balloon Angioplasty e617 6.3.3. Restenosis After BMS e617 6.3.4. Restenosis After DES e617 6.4. Clinical Follow-Up e617 6.4.1. Exercise Testing: Recommendations e617 6.4.2. Activity and Return to Work e618 6.4.3. Cardiac Rehabilitation: Recommendation e618 6.5. Secondary Prevention e618 7. Quality and Performance Considerations e618 7.1. Quality and Performance: Recommendations e618 7.2. Training e619 7.3. Certification and Maintenance of Certification: Recommendation e619 7.4. Operator and Institutional Competency and Volume: Recommendations e619 7.5. Participation in ACC NCDR or National Quality Database e620 8. Future Challenges e620 References e620 Appendix 1. Author Relationships With Industry and Other Entities (Relevant) e643 Appendix 2. Reviewer Relationships With Industry and Other Entities (Relevant) e645 Appendix 3. Abbreviation List e648 Appendix 4. Additional Tables/Figures e649 Preamble The medical profession should play a central role in evalu- ating the evidence related to drugs, devices, and procedures for the detection, management, and prevention of disease. When properly applied, expert analysis of available data on the benefits and risks of these therapies and procedures can improve the quality of care, optimize patient outcomes, and favorably affect costs by focusing resources on the most effective strategies. An organized and directed approach to a thorough review of evidence has resulted in the production of clinical practice guidelines that assist physicians in selecting the best management strategy for an individual patient. Moreover, clinical practice guidelines can provide a founda- tion for other applications, such as performance measures, appropriate use criteria, and both quality improvement and clinical decision support tools. The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly produced guidelines in the area of cardiovascular disease since 1980. The ACCF/AHA Task Force on Practice Guide- lines (Task Force), charged with developing, updating, and revising practice guidelines for cardiovascular diseases and procedures, directs and oversees this effort. Writing commit- tees are charged with regularly reviewing and evaluating all available evidence to develop balanced, patient-centric rec- ommendations for clinical practice. Experts in the subject under consideration are selected by the ACCF and AHA to examine subject-specific data and write guidelines in partnership with representatives from other medical organizations and specialty groups. Writing committees are asked to perform a formal literature review; weigh the strength of evidence for or against particular tests, treatments, or procedures; and include estimates of expected outcomes where such data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that may influence the choice of tests or therapies are considered. When available, information from studies on cost is consid- ered, but data on efficacy and outcomes constitute the primary basis for the recommendations contained herein. In analyzing the data and developing recommendations and supporting text, the writing committee uses evidence-based methodologies developed by the Task Force.1 The Class of Recommendation (COR) is an estimate of the size of the treatment effect considering risks versus benefits in addition to evidence and/or agreement that a given treatment or procedure is or is not useful/effective or in some situations may cause harm. The Level of Evidence (LOE) is an estimate of the certainty or precision of the treatment effect. The writing committee reviews and ranks evidence supporting each recommendation with the weight of evidence ranked as LOE A, B, or C according to specific definitions that are included in Table 1. Studies are identified as observational, retrospective, prospective, or randomized where appropriate. For certain conditions for which inadequate data are avail- able, recommendations are based on expert consensus and clinical experience and are ranked as LOE C. When recom- mendations at LOE C are supported by historical clinical data, appropriate references (including clinical reviews) are cited if available. For issues for which sparse data are available, a survey of current practice among the clinicians on the writing committee is the basis for LOE C recommenda- tions and no references are cited. The schema for COR and LOE is summarized in Table 1, which also provides sug- gested phrases for writing recommendations within each COR. A new addition to this methodology is separation of the Table 1. Applying Classification of Recommendations and Level of Evidence A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective. *Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. For comparative effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated. Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e577 Class III recommendations to delineate if the recommenda- tion is determined to be of no benefit or is associated with harm to the patient. In addition, in view of the increasing number of comparative effectiveness studies, comparator verbs and suggested phrases for writing recommendations for the comparative effectiveness of one treatment or strategy versus another have been added for COR I and IIa, LOE A or B only. In view of the advances in medical therapy across the spectrum of cardiovascular diseases, the Task Force has designated the term guideline-directed medical therapy (GDMT) to represent optimal medical therapy as defined by ACCF/AHA guideline recommended therapies (primarily Class I). This new term, GDMT, will be used herein and throughout all future guidelines. Because the ACCF/AHA practice guidelines address pa- tient populations (and healthcare providers) residing in North America, drugs that are not currently available in North America are discussed in the text without a specific COR. For studies performed in large numbers of subjects outside North America, each writing committee reviews the potential influ- ence of different practice patterns and patient populations on the treatment effect and relevance to the ACCF/AHA target population to determine whether the findings should inform a specific recommendation. The ACCF/AHA practice guidelines are intended to assist healthcare providers in clinical decision making by describ- ing a range of generally acceptable approaches to the diag- nosis, management, and prevention of specific diseases or conditions. The guidelines attempt to define practices that meet the needs of most patients in most circumstances. The ultimate judgment regarding care of a particular patient must be made by the healthcare provider and patient in light of all the circumstances presented by that patient. As a result, situations may arise for which deviations from these guide- lines may be appropriate. Clinical decision making should involve consideration of the quality and availability of exper- tise in the area where care is provided. When these guidelines are used as the basis for regulatory or payer decisions, the goal should be improvement in quality of care. The Task Force recognizes that situations arise in which additional data are needed to inform patient care more effectively; these areas will be identified within each respective guideline when appropriate. Prescribed courses of treatment in accordance with these recommendations are effective only if followed. Because lack of patient understanding and adherence may adversely affect outcomes, physicians and other healthcare providers should make every effort to engage the patient s active participation in prescribed medical regimens and lifestyles. In addition, patients should be informed of the risks, benefits, and alternatives to a particular treatment and be involved in shared decision making whenever feasible, particularly for COR IIa and IIb, where the benefit-to-risk ratio may be lower. The Task Force makes every effort to avoid actual, potential, or perceived conflicts of interest that may arise as a result of industry relationships or personal interests among the members of the writing committee. All writing committee members and peer reviewers of the guideline are asked to disclose all such current relationships, as well as those existing 12 months previously. In December 2009, the ACCF and AHA implemented a new policy for relationships with industry and other entities (RWI) that requires the writing committee chair plus a minimum of 50% of the writing committee to have no relevant RWI (Appendix 1 for the ACCF/AHA definition of relevance). These statements are reviewed by the Task Force and all members during each conference call and/or meeting of the writing committee and are updated as changes occur. All guideline recommendations require a confidential vote by the writing committee and must be approved by a consensus of the voting members. Members are not permitted to write, and must recuse themselves from voting on, any recommendation or section to which their RWI apply. Members who recused themselves from voting are indicated in the list of writing committee members, and section recusals are noted in Appendix 1. Authors and peer reviewers RWI pertinent to this guideline are disclosed in Appendixes 1 and 2, respectively. Additionally, to ensure complete transparency, writing committee members compre- hensive disclosure information including RWI not pertinent to this document is available as an online supplement. Comprehensive disclosure information for the Task Force is also available online at www.cardiosource.org/ACC/About-ACC/ Leadership/Guidelines-and-Documents-Task-Forces.aspx. The work of the writing committee was supported exclusively by the ACCF, AHA, and the Society for Cardiovascular Angiography and Interventions (SCAI) without commercial support. Writing com- mittee members volunteered their time for this activity. In an effort to maintain relevance at the point of care for practicing physicians, the Task Force continues to oversee an ongoing process improvement initiative. As a result, in response to pilot projects, several changes to these guidelines will be apparent, including limited narrative text, a focus on summary and evidence tables (with references linked to abstracts in PubMed) and more liberal use of summary recommendation tables (with references that support LOE) to serve as a quick reference. In April 2011, the Institute of Medicine released 2 reports: Finding What Works in Health Care: Standards for System- atic Reviews and Clinical Practice Guidelines We Can Trust.2,3 It is noteworthy that the ACCF/AHA guidelines were cited as being compliant with many of the standards that were proposed. A thorough review of these reports and of our current methodology is under way, with further enhance- ments anticipated. The recommendations in this guideline are considered current until they are superseded by a focused update or the full-text guideline is revised. Guidelines are official policy of both the ACCF and AHA. Alice K. Jacobs, MD, FACC, FAHA, Chair ACCF/AHA Task Force on Practice Guidelines 1.1. Methodology and Evidence Review The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted through November 2010, as well as selected other references through August 2011. Searches were limited to studies, reviews, and other evidence conducted in human subjects and that were published in English. Key search words included but were not limited to the following: ad hoc angioplasty, angioplasty, balloon angioplasty, clinical trial, coronary stenting, delayed angioplasty, meta-analysis, per- cutaneous transluminal coronary angioplasty, randomized controlled trial (RCT), percutaneous coronary intervention (PCI) and angina, angina reduction, antiplatelet therapy, bare-metal stents (BMS), cardiac rehabilitation, chronic stable angina, complication, coronary bifurcation lesion, coronary calcified lesion, coronary chronic total occlusion (CTO), coronary ostial lesions, coronary stent (BMS and drug-eluting stents [DES]; and BMS versus DES), diabetes, distal embolization, distal protection, elderly, ethics, late stent thrombosis, medical therapy, microembolization, mor- tality, multiple lesions, multi-vessel, myocardial infarction (MI), non ST-elevation myocardial infarction (NSTEMI), no-reflow, optical coherence tomography, proton pump in- hibitor (PPI), return to work, same-day angioplasty and/or stenting, slow flow, stable ischemic heart disease (SIHD), staged angioplasty, STEMI, survival, and unstable angina (UA). Additional searches cross-referenced these topics with the following subtopics: anticoagulant therapy, contrast ne- phropathy, PCI-related vascular complications, unprotected left main PCI, multivessel coronary artery disease (CAD), adjunctive percutaneous interventional devices, percutaneous hemodynamic support devices, and secondary prevention. Additionally, the committee reviewed documents related to the subject matter previously published by the ACCF and AHA. References selected and published in this document are representative and not all-inclusive. To provide clinicians with a comprehensive set of data, whenever deemed appropriate or when published, the abso- lute risk difference and number needed to treat or harm will be provided in the guideline, along with confidence intervals (CIs) and data related to the relative treatment effects such as odds ratio (OR), relative risk, hazard ratio (HR), or incidence rate ratio. The focus of this guideline is the safe, appropriate, and efficacious performance of PCI. The risks of PCI must be balanced against the likelihood of improved survival, symp- toms, or functional status. This is especially important in patients with SIHD. 1.2. Organization of the Writing Committee The committee was composed of physicians with expertise in interventional cardiology, general cardiology, critical care cardiology, cardiothoracic surgery, clinical trials, and health services research. The committee included representatives from the ACCF, AHA, and SCAI. 1.3. Document Review and Approval This document was reviewed by 2 official reviewers nomi- nated by the ACCF, AHA, and SCAI, as well as 21 individual content reviewers (including members of the ACCF Interven- tional Scientific Council and ACCF Surgeons Scientific Council). All information on reviewers RWI was distributed to the writing committee and is published in this document (Appendix 2). This document was approved for publication by the governing bodies of the ACCF, AHA, and SCAI. 1.4. PCI Guidelines: History and Evolution In 1982, a 2-page manuscript titled Guidelines for the Performance of Percutaneous Transluminal Coronary Angio- plasty was published in Circulation.4 The document, which addressed the specific expertise and experience physicians should have to perform balloon angioplasty, as well as laboratory requirements and the need for surgical support, was written by an ad hoc group whose members included Andreas Gru ntzig. In 1980, the ACC and the AHA estab- lished the Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures, which was charged with the development of guidelines related to the role of new therapeutic approaches and of specific noninvasive and inva- sive procedures in the diagnosis and management of cardio- vascular disease. The first ACC/AHA Task Force report on guidelines for coronary balloon angioplasty was published in 1988.5 The 18-page document discussed and made recom- mendations about lesion classification and success rates, indications for and contraindications to balloon angioplasty, institutional review of angioplasty procedures, ad hoc angio- plasty after angiography, and on-site surgical backup. Further iterations of the guidelines were published in 1993,6 2001,7 and 2005.8 In 2007 and 2009, focused updates to the guideline were published to expeditiously address new study results and recent changes in the field of interventional cardiology.9,10 The 2009 focused update is notable in that there was direct collaboration between the writing commit- tees for the STEMI guidelines and the PCI guidelines, resulting in a single publication of focused updates on STEMI The evolution of the PCI guideline reflects the growth of knowledge in the field and parallels the many advances and innovations in the field of interventional cardiology, includ- ing primary PCI, BMS and DES, intravascular ultrasound (IVUS) and physiologic assessments of stenosis, and newer antiplatelet and anticoagulant therapies. The 2011 iteration of the guideline continues this process, addressing ethical as- pects of PCI, vascular access considerations, CAD revascu- larization including hybrid revascularization, revasculariza- tion before noncardiac surgery, optical coherence tomography, advanced hemodynamic support devices, no- reflow therapies, and vascular closure devices. Most of this document is organized according to patient flow, consisting of preprocedural considerations, procedural considerations, and postprocedural considerations. In a major undertaking, the STEMI, PCI, and coronary artery bypass graft (CABG) surgery guidelines were written concurrently, with additional collaboration with the SIHD guideline writing committee, allowing greater collaboration between the different writing committees on topics such as PCI in STEMI and revascular- ization strategies in patients with CAD (including unpro- tected left main PCI, multivessel disease revascularization, and hybrid procedures). In accordance with direction from the Task Force and feedback from readers, in this iteration of the guideline, the text has been shortened, with an emphasis on summary Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e579 statements rather than detailed discussion of numerous indi- vidual trials. Online supplemental evidence and summary tables have been created to document the studies and data considered for new or changed guideline recommendations. 2. CAD Revascularization Recommendations and text in this section are the result of extensive collaborative discussions between the PCI and CABG writing committees, as well as key members of the SIHD and UA/NSTEMI writing committees. Certain issues, such as older versus more contemporary studies, primary analyses versus subgroup analyses, and prospective versus post hoc analyses, have been carefully weighed in designating COR and LOE; they are addressed in the appropriate corre- sponding text. The goals of revascularization for patients with CAD are to 1) improve survival and/or 2) relieve symptoms. Revascularization recommendations in this section are predominantly based on studies of patients with symptomatic SIHD and should be interpreted in this context. As discussed later in this section, recommendations on the type of revas- cularization are, in general, applicable to patients with UA/ NSTEMI. In some cases (eg, unprotected left main CAD), specific recommendations are made for patients with UA/ NSTEMI or STEMI. Historically, most studies of revascularization have been based on and reported according to angiographic criteria. Most studies have defined a significant stenosis as 70% diameter narrowing; therefore, for revascularization decisions and recommendations in this section, a significant stenosis has been defined as 70% diameter narrowing ( 50% for left main CAD). Physiological criteria, such as an assessment of fractional flow reserve (FFR), has been used in deciding when revascularization is indicated. Thus, for recommenda- tions about revascularization in this section, coronary steno- ses with FFR 0.80 can also be considered to be As noted, the revascularization recommendations have been formulated to address issues related to 1) improved survival and/or 2) improved symptoms. When one method of revascularization is preferred over the other for improved survival, this consideration, in general, takes precedence over improved symptoms. When discussing options for revascu- larization with the patient, he or she should understand when the procedure is being performed in an attempt to improve symptoms, survival, or both. Although some results from the SYNTAX (Synergy be- tween Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) study are best characterized as subgroup analyses and hypothesis generating, SYNTAX nonetheless represents the latest and most comprehensive comparison of PCI and CABG.13,14 Therefore, the results of SYNTAX have been considered appropriately when formulating our revas- cularization recommendations. Although the limitations of using the SYNTAX score for certain revascularization rec- ommendations are recognized, the SYNTAX score is a reasonable surrogate for the extent of CAD and its complex- ity and serves as important information that should be considered when making revascularization decisions. Recom- mendations that refer to SYNTAX scores use them as surrogates for the extent and complexity of CAD. Revascularization recommendations to improve survival and symptoms are provided in the following text and are summarized in Tables 2 and 3. References to studies com- paring revascularization with medical therapy are presented when available for each anatomic subgroup. See Online Data Supplements 1 and 2 for additional data regarding the survival and symptomatic benefits with CABG or PCI for different anatomic subsets. 2.1. Heart Team Approach to Revascularization Decisions: Recommendations Class I 1. A Heart Team approach to revascularization is recommended in patients with unprotected left main or complex CAD.14 16 (Level of Evidence: C) Class IIa 1. Calculation of the Society of Thoracic Surgeons (STS) and SYNTAX scores is reasonable in pa- tients with unprotected left main and complex CAD.13,14,17 22 (Level of Evidence: B) One protocol used in RCTs14 16,23 often involves a multidis- ciplinary approach referred to as the Heart Team. Composed of an interventional cardiologist and a cardiac surgeon, the Heart Team 1) reviews the patient s medical condition and coronary anatomy, 2) determines that PCI and/or CABG are technically feasible and reasonable, and 3) discusses revas- cularization options with the patient before a treatment strategy is selected. Support for using a Heart Team approach comes from reports that patients with complex CAD referred specifically for PCI or CABG in concurrent trial registries have lower mortality rates than those randomly assigned to PCI or CABG in controlled trials.15,16 The SIHD, PCI, and CABG guideline writing committees endorse a Heart Team approach in patients with unprotected left main CAD and/or complex CAD in whom the optimal revascularization strategy is not straightforward. A collabor- ative assessment of revascularization options, or the decision to treat with GDMT without revascularization, involving an interventional cardiologist, a cardiac surgeon, and (often) the patient s general cardiologist, followed by discussion with the patient about treatment options, is optimal. Particularly in patients with SIHD and unprotected left main and/or complex CAD for whom a revascularization strategy is not straight- forward, an approach has been endorsed that involves termi- nating the procedure after diagnostic coronary angiography is completed: this allows a thorough discussion and affords both the interventional cardiologist and cardiac surgeon the oppor- tunity to discuss revascularization options with the patient. Because the STS score and the SYNTAX score have been shown to predict adverse outcomes in patients undergoing CABG and PCI, respectively, calculation of these scores is often useful in making revascularization decisions.13,14,17 22 Table 2. Revascularization to Improve Survival Compared With Medical Therapy Anatomic Setting COR LOE References UPLM or complex CAD CABG and PCI I Heart Team approach recommended C 14 16 CABG and PCI IIa Calculation of STS and SYNTAX scores B 13,14,17 22 UPLM* CABG I B 24 30 PCI IIa For SIHD when both of the following are present Anatomic conditions associated with a low risk of PCI procedural complications and a high likelihood of good long-term outcome (eg, a low SYNTAX score of 22, ostial or trunk left main CAD) Clinical characteristics that predict a significantly increased risk of adverse surgical outcomes (eg, STS-predicted risk of operative mortality 5%) IIa For UA/NSTEMI if not a CABG candidate B 13,36 39,44,45,47 49 IIa For STEMI when distal coronary flow is TIMI flow grade 3 and PCI can be performed more rapidly and safely than CABG IIb For SIHD when both of the following are present Anatomic conditions associated with a low to intermediate risk of PCI procedural complications and an intermediate to high likelihood of good long-term outcome (eg, low-intermediate SYNTAX score of 33, bifurcation left main CAD) Clinical characteristics that predict an increased risk of adverse surgical outcomes (eg, moderate-severe COPD, disability from prior stroke, or prior cardiac surgery; STS-predicted risk of operative mortality 2%) III: Harm For SIHD in patients (versus performing CABG) with unfavorable anatomy for PCI and who are good candidates for CABG 3-vessel disease with or without proximal LAD artery disease* CABG I B 26,30,53 56 IIa It is reasonable to choose CABG over PCI in patients with complex 3-vessel CAD (eg, SYNTAX score 22) who are good candidates for CABG PCI IIb Of uncertain benefit B 26,46,53,56,82 2-vessel disease with proximal LAD artery disease* CABG I B 26,30,53 56 PCI IIb Of uncertain benefit B 26,53,56,82 2-vessel disease without proximal LAD artery disease* CABG IIa With extensive ischemia B 60 63 IIb Of uncertain benefit without extensive ischemia C 56 PCI IIb Of uncertain benefit B 26,53,56,82 1-vessel proximal LAD artery disease CABG IIa With LIMA for long-term benefit B 30,56,69,70 PCI IIb Of uncertain benefit B 26,53,56,82 1-vessel disease without proximal LAD artery involvement CABG III: Harm B 30,53,60,61,94 98 PCI III: Harm B 30,53,60,61,94 98 LV dysfunction CABG IIb EF 35% without significant left main CAD B 30,64 68,83,84 PCI Insufficient data N/A Survivors of sudden cardiac death with presumed ischemia-mediated VT CABG I B 57 59 PCI I C 57 No anatomic or physiologic criteria for revascularization CABG III: Harm B 30,53,60,61,94 98 PCI III: Harm B 30,53,60,61,94 98 *In patients with multivessel disease who also have diabetes, it is reasonable to choose CABG (with LIMA) over PCI62,74 81 (Class IIa; LOE: B). CABG indicates coronary artery bypass graft; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; COR, class of recommendation; EF, ejection fraction; LAD, left anterior descending; LIMA, left internal mammary artery; LOE, level of evidence; LV, left ventricular; N/A, not applicable; PCI, percutaneous coronary intervention; SIHD, stable ischemic heart disease; STEMI, ST-elevation myocardial infarction; STS, Society of Thoracic Surgeons; SYNTAX, Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery; TIMI, Thrombolysis in Myocardial Infarction; UA/NSTEMI, unstable angina/non ST-elevation myocardial infarction; UPLM, unprotected left main disease; and VT, ventricular tachycardia. Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e581 2.2. Revascularization to Improve Survival: Recommendations Left Main CAD Revascularization Class I 1. CABG to improve survival is recommended for patients with significant (>50% diameter stenosis) left main coronary artery stenosis.24 30 (Level of Evidence: B) Class IIa 1. PCI to improve survival is reasonable as an alterna- tive to CABG in selected stable patients with signif- icant (>50% diameter stenosis) unprotected left main CAD with: 1) anatomic conditions associated with a low risk of PCI procedural complications and a high likelihood of good long-term outcome (eg, a low SYNTAX score [<22], ostial or trunk left main CAD); and 2) clinical characteristics that predict a significantly increased risk of adverse surgical out- comes (eg, STS-predicted risk of operative mortality >5%).13,17,19,23,31 48 (Level of Evidence: B) 2. PCI to improve survival is reasonable in patients with UA/NSTEMI when an unprotected left main coronary artery is the culprit lesion and the patient is not a candidate for CABG.13,36 39,44,45,47 49 (Level of Evidence: B) 3. PCI to improve survival is reasonable in patients with acute STEMI when an unprotected left main coronary artery is the culprit lesion, distal coronary flow is less than TIMI (Thrombolysis In Myocardial Infarction) grade 3, and PCI can be performed more rapidly and safely than CABG.33,50,51 (Level of Evi- dence: C) Class IIb 1. PCI to improve survival may be reasonable as an alternative to CABG in selected stable patients with significant (>50% diameter stenosis) unprotected left main CAD with: 1) anatomic conditions associ- ated with a low to intermediate risk of PCI proce- dural complications and an intermediate to high likelihood of good long-term outcome (eg, low- intermediate SYNTAX score of <33, bifurcation left main CAD); and 2) clinical characteristics that predict an increased risk of adverse surgical out- comes (eg, moderate-severe chronic obstructive pul- monary disease, disability from previous stroke, or previous cardiac surgery; STS-predicted risk of operative mortality >2%).13,17,19,23,31 48,52 (Level of Evidence: B) Class III: HARM 1. PCI to improve survival should not be performed in stable patients with significant (>50% diameter stenosis) unprotected left main CAD who have un- favorable anatomy for PCI and who are good can- didates for CABG.13,17,19,24 32 (Level of Evidence: B) Non Left Main CAD Revascularization Class I 1. CABG to improve survival is beneficial in patients with significant (>70% diameter) stenoses in 3 major coronary arteries (with or without involve- ment of the proximal left anterior descending [LAD] artery) or in the proximal LAD plus 1 other major coronary artery.26,30,53 56 (Level of Evidence: B) 2. CABG or PCI to improve survival is beneficial in survivors of sudden cardiac death with presumed ischemia-mediated ventricular tachycardia caused by significant (>70% diameter) stenosis in a major coronary artery. (CABG Level of Evidence: B57 59; PCI Level of Evidence: C57) Class IIa 1. CABG to improve survival is reasonable in patients with significant (>70% diameter) stenoses in 2 major coronary arteries with severe or extensive Table 3. Revascularization to Improve Symptoms With Significant Anatomic (>50% Left Main or >70% Non Left Main CAD) or Physiological (FFR <0.80) Coronary Artery Stenoses Clinical Setting COR LOE References 1 significant stenoses amenable to revascularization and unacceptable angina despite GDMT I CABG I PCI 1 significant stenoses and unacceptable angina in whom GDMT cannot be implemented because of medication contraindications, adverse effects, or patient preferences IIa CABG IIa PCI C N/A Previous CABG with 1 significant stenoses associated with ischemia and unacceptable angina despite GDMT IIa PCI C 86,89,92 IIb CABG C 93 Complex 3-vessel CAD (eg, SYNTAX score 22) with or without involvement of the proximal LAD artery and a good candidate for CABG IIa CABG preferred over PCI B 32,46,56,71,72 Viable ischemic myocardium that is perfused by coronary arteries that are not amenable to grafting IIb TMR as an adjunct to CABG No anatomic or physiologic criteria for revascularization III: Harm CABG III: Harm PCI C N/A CABG indicates coronary artery bypass graft; CAD, coronary artery disease; COR, class of recommendation; FFR, fractional flow reserve; GDMT, guideline-directed medical therapy; LOE, level of evidence; N/A, not applicable; PCI, percutaneous coronary intervention; SYNTAX, Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery; and TMR, transmyocardial laser revascularization. myocardial ischemia (eg, high-risk criteria on stress testing, abnormal intracoronary hemodynamic eval- uation, or >20% perfusion defect by myocardial perfusion stress imaging) or target vessels supplying a large area of viable myocardium.60 63 (Level of Evidence: B) 2. CABG to improve survival is reasonable in patients with mild-moderate left ventricular (LV) systolic dysfunction (ejection fraction [EF] 35% to 50%) and significant (>70% diameter stenosis) multi-vessel CAD or proximal LAD coronary artery stenosis, when viable myocardium is present in the region of intended revascularization.30,64 68 (Level of Evi- dence: B) 3. CABG with a left internal mammary artery (LIMA) graft to improve survival is reasonable in patients with significant (>70% diameter) stenosis in the proximal LAD artery and evidence of extensive ischemia.30,56,69,70 (Level of Evidence: B) 4. It is reasonable to choose CABG over PCI to im- prove survival in patients with complex 3-vessel CAD (eg, SYNTAX score >22), with or without involvement of the proximal LAD artery who are good candidates for CABG.32,46,56,71,72 (Level of Evi- dence: B) 5. CABG is probably recommended in preference to PCI to improve survival in patients with multivessel CAD and diabetes mellitus, particularly if a LIMA graft can be anastomosed to the LAD artery.62,74 81 (Level of Evidence: B) Class IIb 1. The usefulness of CABG to improve survival is uncertain in patients with significant (>70%) diam- eter stenoses in 2 major coronary arteries not involv- ing the proximal LAD artery and without extensive ischemia.56 (Level of Evidence: C) 2. The usefulness of PCI to improve survival is uncer- tain in patients with 2- or 3-vessel CAD (with or without involvement of the proximal LAD artery) or 1-vessel proximal LAD disease.26,53,56,82 (Level of Evidence: B) 3. CABG might be considered with the primary or sole intent of improving survival in patients with SIHD with severe LV systolic dysfunction (EF <35%) whether or not viable myocardium is present.30,64 68,83,84 (Level of Evidence: B) 4. The usefulness of CABG or PCI to improve survival is uncertain in patients with previous CABG and extensive anterior wall ischemia on noninvasive test- ing.85 93 (Level of Evidence: B) Class III: HARM 1. CABG or PCI should not be performed with the primary or sole intent to improve survival in pa- tients with SIHD with 1 or more coronary stenoses that are not anatomically or functionally significant (eg, <70% diameter non left main coronary artery stenosis, FFR >0.80, no or only mild ischemia on noninvasive testing), involve only the left circumflex or right coronary artery, or subtend only a small area of viable myocardium.30,53,60,61,94 98 (Level of Evidence: B) 2.3. Revascularization to Improve Symptoms: Recommendations Class I 1. CABG or PCI to improve symptoms is beneficial in patients with 1 or more significant (>70% diameter) coronary artery stenoses amenable to revasculariza- tion and unacceptable angina despite GDMT.82,99 108 (Level of Evidence: A) Class IIa 1. CABG or PCI to improve symptoms is reasonable in patients with 1 or more significant (>70% diameter) coronary artery stenoses and unacceptable angina for whom GDMT cannot be implemented because of medication contraindications, adverse effects, or pa- tient preferences. (Level of Evidence: C) 2. PCI to improve symptoms is reasonable in patients with previous CABG, 1 or more significant (>70% diameter) coronary artery stenoses associated with ischemia, and unacceptable angina despite GDMT.86,89,92 (Level of Evidence: C) 3. It is reasonable to choose CABG over PCI to im- prove symptoms in patients with complex 3-vessel CAD (eg, SYNTAX score >22), with or without involvement of the proximal LAD artery who are good candidates for CABG.32,46,56,72,73 (Level of Evi- dence: B) Class IIb 1. CABG to improve symptoms might be reasonable for patients with previous CABG, 1 or more signif- icant (>70% diameter) coronary artery stenoses not amenable to PCI, and unacceptable angina despite GDMT.93 (Level of Evidence: C) 2. Transmyocardial laser revascularization (TMR) performed as an adjunct to CABG to improve symptoms may be reasonable in patients with viable ischemic myocardium that is perfused by arteries that are not amenable to grafting.109 113 (Level of Evidence: B) Class III: HARM 1. CABG or PCI to improve symptoms should not be performed in patients who do not meet anatomic (>50% diameter left main or >70% non left main stenosis diameter) or physiological (eg, abnormal FFR) criteria for revascularization. (Level of Evi- dence: C) 2.4. CABG Versus Contemporaneous Medical Therapy In the 1970s and 1980s, 3 RCTs established the survival benefit of CABG compared with contemporaneous (although minimal by current standards) medical therapy without revas- cularization in certain subjects with stable angina: the Veter- Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e583 ans Affairs Cooperative Study,114 European Coronary Sur- gery Study,55 and CASS (Coronary Artery Surgery Study).115 Subsequently, a 1994 meta-analysis of 7 studies that random- ized a total of 2649 patients to medical therapy or CABG30 showed that CABG offered a survival advantage over medi- cal therapy for patients with left main or 3-vessel CAD. The studies also established that CABG is more effective than medical therapy for relieving anginal symptoms. These stud- ies have been replicated only once during the past decade. In MASS II (Medicine, Angioplasty, or Surgery Study II), patients with multivessel CAD who were treated with CABG were less likely than those treated with medical therapy to have a subsequent MI, need additional revascularization, or experience cardiac death in the 10 years after Surgical techniques and medical therapy have improved substantially during the intervening years. As a result, if CABG were to be compared with GDMT in RCTs today, the relative benefits for survival and angina relief observed several decades ago might no longer be observed. Con- versely, the concurrent administration of GDMT may sub- stantially improve long-term outcomes in patients treated with CABG in comparison with those receiving medical therapy alone. In the BARI 2D (Bypass Angioplasty Revas- cularization Investigation 2 Diabetes) trial of patients with diabetes mellitus, no significant difference in risk of mortality in the cohort of patients randomized to GDMT plus CABG or GDMT alone was observed, although the study was not powered for this endpoint, excluded patients with significant left main CAD, and included only a small percentage of patients with proximal LAD artery disease or LV ejection fraction (LVEF) 0.50.116 The PCI and CABG guideline writing committees endorse the performance of the ISCH- EMIA (International Study of Comparative Health Effective- ness with Medical and Invasive Approaches) trial, which will provide contemporary data on the optimal management strat- egy (medical therapy or revascularization with CABG or PCI) of patients with SIHD, including multivessel CAD, and moderate to severe ischemia. 2.5. PCI Versus Medical Therapy Although contemporary interventional treatments have low- ered the risk of restenosis compared with earlier techniques, meta-analyses have failed to show that the introduction of BMS confers a survival advantage over balloon angio- plasty117 119 or that the use of DES confers a survival advantage over BMS.119,120 No study to date has demonstrated that PCI in patients with SIHD improves survival rates.26,53,56,82,116,119,121 124 Neither COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation)82 nor BARI 2D,116 which treated all patients with contemporary optimal medical ther- apy, demonstrated any survival advantage with PCI, although these trials were not specifically powered for this endpoint. Although 1 large analysis evaluating 17 RCTs of PCI versus medical therapy (including 5 trials of subjects with acute coronary syndromes [ACS]) found a 20% reduction in death with PCI compared with medical therapy,123 2 other large analyses did not.119,122 An evaluation of 13 studies reporting the data from 5442 patients with nonacute CAD showed no advantage of PCI over medical therapy for the individual endpoints of all-cause death, cardiac death or MI, or nonfatal MI.124 Evaluation of 61 trials of PCI conducted over several decades shows that despite improvements in PCI technology and pharmacotherapy, PCI has not been demonstrated to reduce the risk of death or MI in patients without recent The findings from individual studies and systematic re- views of PCI versus medical therapy can be summarized as follows: PCI reduces the incidence of angina.82,99,104,107,108,125 PCI has not been demonstrated to improve survival in PCI may increase the short-term risk of MI.82,121,125,126 PCI does not lower the long-term risk of MI.82,116,119,121,122,126 2.6. CABG Versus PCI The results of 26 RCTs comparing CABG and PCI have been published: Of these, 9 compared CABG with balloon angio- plasty,75,105,128 142 14 compared CABG with BMS implanta- tion,88,143 160 and 3 compared CABG with DES 2.6.1. CABG Versus Balloon Angioplasty or BMS A systematic review of the 22 RCTs comparing CABG with balloon angioplasty or BMS implantation concluded the 1. Survival was similar for CABG and PCI (with balloon angioplasty or BMS) at 1 year and 5 years. Survival was similar for CABG and PCI in subjects with 1-vessel CAD (including those with disease of the proximal portion of the LAD artery) or multivessel CAD. 2. Incidence of MI was similar at 5 years after randomization. 3. Procedural stroke occurred more commonly with CABG than with PCI (1.2% versus 0.6%). 4. Relief of angina was accomplished more effectively with CABG than with PCI 1 year after randomization and 5 years after randomization. 5. During the first year after randomization, repeat coro- nary revascularization was performed less often after CABG than after PCI (3.8% versus 26.5%). This was also demonstrated after 5 years of follow-up (9.8% versus 46.1%). This difference was more pronounced with balloon angioplasty than with BMS. A collaborative analysis of data from 10 RCTs comparing CABG with balloon angioplasty (6 trials) or with BMS implantation (4 trials)164 permitted subgroup analyses of the data from the 7812 patients. No difference was noted with regard to mortality rate 5.9 years after randomization or the composite endpoint of death or MI. Repeat revascularization and angina were noted more frequently in those treated with balloon angioplasty or BMS implantation.164 The major new observation of this analysis was that CABG was associated with better outcomes in patients with diabetes mellitus and in those 65 years old. Of interest, the relative outcomes of CABG and PCI were not influenced by other patient charac- teristics, including the number of diseased coronary arteries. The aforementioned meta-analysis and systematic re- view163,164 comparing CABG and balloon angioplasty or BMS implantation were limited in several ways: 1. Many trials did not report outcomes for other important patient subsets. For example, the available data are insufficient to determine if race, obesity, renal dysfunc- tion, peripheral arterial disease, or previous coronary revascularization affected the comparative outcomes of CABG and PCI. 2. Most of the patients enrolled in these trials were male, and most had 1- or 2-vessel CAD and normal LV systolic function (EF 50%) subjects known to be unlikely to derive a survival benefit and less likely to experience complications after CABG.30 3. The patients enrolled in these trials represented only a small fraction (generally 5% to 10%) of those who were screened. For example, most screened patients with 1-vessel CAD and many with 3-vessel CAD were not considered for randomization. See Online Data Supplements 3 and 4 for additional data comparing CABG with PCI. 2.6.2. CABG Versus DES Although the results of 9 observational studies comparing CABG and DES implantation have been published,32,165 172 most of them had short (12 to 24 months) follow-up periods. In a meta-analysis of 24 268 patients with multivessel CAD treated with CABG or DES,173 the incidences of death and MI were similar for the 2 procedures, but the frequency with which repeat revascularization was performed was roughly 4 times higher after DES implantation. Only 1 large RCT comparing CABG and DES implantation has been published. The SYNTAX trial randomly assigned 1800 patients (of a total of 4337 who were screened) to receive DES or CABG.14,46 Major adverse cardiac events (MACE), a com- posite of death, stroke, MI, or repeat revascularization during the 3 years after randomization, occurred in 20.2% of CABG patients and 28.0% of those undergoing DES implantation (P 0.001). The rates of death and stroke were similar; however, MI (3.6% for CABG, 7.1% for DES) and repeat revascularization (10.7% for CABG, 19.7% for DES) were more likely to occur with DES implantation.46 In SYNTAX, the extent of CAD was assessed using the SYNTAX score, which is based on the location, severity, and extent of coronary stenoses, with a low score indicating less complicated anatomic CAD. In post hoc analyses, a low score was defined as 22; intermediate, 23 to 32; and high, 33. The occurrence of MACE correlated with the SYNTAX score for DES patients but not for those undergoing CABG. At 12-month follow-up, the primary endpoint was similar for CABG and DES in those with a low SYNTAX score. In contrast, MACE occurred more often after DES implantation than after CABG in those with an intermediate or high SYN- TAX score.14 At 3 years of follow-up, the mortality rate was greater in subjects with 3-vessel CAD treated with PCI than in those treated with CABG (6.2% versus 2.9%). The differences in MACE between those treated with PCI or CABG increased with an increasing SYNTAX score (Figure 1).46 Although the utility of using a SYNTAX score in everyday clinical practice remains uncertain, it seems reasonable to conclude from SYNTAX and other data that outcomes of patients undergoing PCI or CABG in those with relatively uncomplicated and lesser degrees of CAD are comparable, whereas in those with complex and diffuse CAD, CABG appears to be preferable.46 See Online Data Supplements 5 and 6 for additional data comparing CABG with DES. 2.7. Left Main CAD 2.7.1. CABG or PCI Versus Medical Therapy for Left Main CAD CABG confers a survival benefit over medical therapy in patients with left main CAD. Subgroup analyses from RCTs performed 3 decades ago included 91 patients with left main CAD in the Veterans Administration Cooperative Study.28 A meta-analysis of these trials demonstrated a 66% reduction in relative risk in mortality with CABG, with the benefit extending to 10 years.30 The CASS Registry24 contained data Figure 1. Cumulative incidence of MACE in patients with 3-vessel CAD based on SYNTAX score at 3-year follow-up in the SYNTAX trial treated with either CABG or PCI. CABG indicates coronary artery bypass graft; CAD, coronary artery disease; MACE, major adverse cardiovascular event; PCI, percutaneous coronary intervention; and SYNTAX, Synergy between Percutaneous Coronary Inter- vention with TAXUS and Cardiac Surgery. Adapted with permission from Kappetein.46 Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e585 from 1484 patients with 50% diameter stenosis left main CAD initially treated surgically or nonsurgically. Median survival duration was 13.3 years in the surgical group; and 6.6 years in the medical group. The survival benefit of CABG over medical therapy appeared to extend to 53 asymptomatic patients with left main CAD in the CASS Registry.29 Other therapies that subsequently have been shown to be associated with improved long-term outcome, such as the use of aspirin, statins, and internal mammary artery grafting, were not widely used in that era. RCTs and subgroup analyses that compare PCI with medical therapy in patients with unprotected left main CAD do not exist. 2.7.2. Studies Comparing PCI Versus CABG for Left Main CAD Of all subjects undergoing coronary angiography, approxi- mately 4% are found to have left main CAD,175 80% of whom have significant ( 70% diameter) stenoses in other epicardial coronary arteries. Published cohort studies have found that major clinical outcomes are similar with PCI or CABG 1 year after revascularization and that mortality rates are similar at 1, 2, and 5 years of follow-up; however, the risk of needing target-vessel revascularization is significantly higher with stenting than with CABG. In the SYNTAX trial, 45% of screened patients with unprotected left main CAD had complex disease that pre- vented randomization; 89% of these underwent CABG.13,14 In addition, 705 of the 1800 patients who were randomized had revascularization for unprotected left main CAD. The major- ity of patients with left main CAD and a low SYNTAX score had isolated left main CAD or left main CAD plus 1-vessel CAD; the majority of those with an intermediate score had left main CAD plus 2-vessel CAD; and most of those with a high SYNTAX score had left main CAD plus 3-vessel CAD. At 1 year, rates of all-cause death and MACE were similar for the 2 groups.13 Repeat revascularization rates were higher in the PCI group than the CABG group (11.8% versus 6.5%), but stroke occurred more often in the CABG group (2.7% versus 0.3%). At 3 years of follow-up, the incidence of death in those undergoing left main CAD revascularization with low or intermediate SYNTAX scores ( 32) was 3.7% after PCI and 9.1% after CABG (P 0.03), whereas in those with a high SYNTAX score ( 33), the incidence of death after 3 years was 13.4% after PCI and 7.6% after CABG (P 0.10).46 Because the primary endpoint of SYNTAX was not met (ie, noninferiority comparison of CABG and PCI), these sub- group analyses need to be considered in that context. In the LE MANS (Study of Unprotected Left Main Stenting Versus Bypass Surgery) trial,23 105 patients with left main CAD were randomized to receive PCI or CABG. Although a low proportion of patients treated with PCI received DES (35%) and a low proportion of patients treated with CABG received internal mammary grafts (72%), the outcomes at 30 days and 1 year were similar between the groups. In the PRECOMBAT (Premier of Randomized Com- parison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease) trial of 600 patients with left main disease, the composite endpoint of death, MI, or stroke at 2 years occurred in 4.4% of patients treated with PCI patients and 4.7% of patients treated with CABG, but ischemia-driven target-vessel revascularization was more often required in the patients treated with PCI (9.0% versus 4.2%).52 The results from these 3 RCTs suggest (but do not definitively prove) that major clinical outcomes in selected patients with left main CAD are similar with CABG and PCI at 1- to 2-year follow-up, but repeat revascularization rates are higher after PCI than after CABG. RCTs with extended follow-up of 5 years are required to provide definitive conclusions about the optimal treatment of left main CAD. In a meta-analysis of 8 cohort studies and 2 RCTs,41 death, MI, and stroke occurred with similar frequency in the PCI- and CABG-treated patients at 1, 2, and 3 years of follow-up. Target-vessel revascularization was performed more often in the PCI group at 1 year (OR: 4.36), 2 years (OR: 4.20), and 3 years (OR: 3.30). See Online Data Supplements 7 to 12 for additional data comparing PCI with CABG for left main CAD. 2.7.3. Revascularization Considerations for Left Main CAD Although CABG has been considered the gold standard for unprotected left main CAD revascularization, more recently PCI has emerged as a possible alternative mode of revascu- larization in carefully selected patients. Lesion location is an important determinant when considering PCI for unprotected left main CAD. Stenting of the left main ostium or trunk is more straightforward than treating distal bifurcation or trifur- cation stenoses, which generally requires a greater degree of operator experience and expertise.176 In addition, PCI of bifurcation disease is associated with higher restenosis rates than when disease is confined to the ostium or trunk.39,177 Although lesion location influences technical success and long-term outcomes after PCI, location exerts a negligible influence on the success of CABG. In subgroup analyses, patients with left main CAD and a SYNTAX score 33 with more complex or extensive CAD had a higher mortality rate with PCI than with CABG.46 Physicians can estimate opera- tive risk for all CABG candidates using a standard instru- ment, such as the risk calculator from the STS database. The above considerations are important factors when choosing among revascularization strategies for unprotected left main CAD and have been factored into revascularization recom- mendations. Use of a Heart Team approach has been recom- mended in cases in which the choice of revascularization is not straightforward. As discussed in Section 2.9.7, the ability of the patient to tolerate and comply with dual antiplatelet therapy (DAPT) is also an important consideration in revas- cularization decisions. The 2005 PCI guideline8 recommended routine angio- graphic follow-up 2 to 6 months after stenting for unprotected left main CAD. However, because angiography has limited ability to predict stent thrombosis and the results of SYNTAX suggest good intermediate-term results for PCI in subjects with left main CAD, this recommendation was removed in the 2009 STEMI/PCI focused update.10 Experts have recommended immediate PCI for unprotected left main CAD in the setting of STEMI.51 The impetus for such a strategy is greatest when left main CAD is the site of the culprit lesion, antegrade coronary flow is diminished (eg, TIMI flow grade 0, 1, or 2), the patient is hemodynamically unstable, and it is believed that PCI can be performed more quickly than CABG. When possible, the interventional car- diologist and cardiac surgeon should decide together on the optimal form of revascularization for these subjects, although it is recognized that these patients are usually critically ill and therefore not amenable to a prolonged deliberation or discus- sion of treatment options. 2.8. Proximal LAD Artery Disease A cohort study53 and a meta-analysis30 from the 1990s suggested that CABG confers a survival advantage over contemporaneous medical therapy for patients with disease in the proximal segment of the LAD artery. Cohort studies and RCTs30,133,146,148,161,178 181 as well as collaborative- and meta- analyses164,182 184 showed that PCI and CABG result in similar survival rates in these patients. See Online Data Supplement 13 for additional data regarding proximal LAD artery revascularization. 2.9. Clinical Factors That May Influence the Choice of Revascularization 2.9.1. Diabetes Mellitus An analysis performed in 2009 of data on 7812 patients (1233 with diabetes) in 10 RCTs demonstrated a worse long-term survival rate in patients with diabetes mellitus after balloon angioplasty or BMS implantation than after CABG.164 The BARI 2D trial116 randomly assigned 2368 patients with type 2 diabetes and CAD to undergo intensive medical therapy or prompt revascularization with PCI or CABG, according to whichever was thought to be more appropriate. By study design, those with less extensive CAD more often received PCI, whereas those with more extensive CAD were more likely to be treated with CABG. The study was not designed to compare PCI with CABG. At 5-year follow-up, no differ- ence in rates of survival or MACE between the medical therapy group and those treated with revascularization was noted. In the PCI stratum, no significant difference in MACE between medical therapy and revascularization was demon- strated (DES in 35%; BMS in 56%); in the CABG stratum, MACE occurred less often in the revascularization group. One-year follow-up data from the SYNTAX study demon- strated a higher rate of repeat revascularization in patients with diabetes mellitus treated with PCI than with CABG, driven by a tendency for higher repeat revascularization rates in those with higher SYNTAX scores undergoing PCI.76 In summary, in subjects requiring revascularization for multi- vessel CAD, current evidence supports diabetes mellitus as an important factor when deciding on a revascularization strat- egy, particularly when complex or extensive CAD is present (Figure 2). See Online Data Supplements 14 and 15 for additional data regarding diabetes mellitus. 2.9.2. Chronic Kidney Disease Cardiovascular morbidity and mortality rates are markedly increased in patients with chronic kidney disease (CKD) when compared with age-matched controls without CKD. The mortality rate for patients on hemodialysis is 20% per year, and approximately 50% of deaths among these patients are due to a cardiovascular cause.187,188 To date, randomized comparisons of coronary revascular- ization (with CABG or PCI) and medical therapy in patients with CKD have not been reported. Some, but not all, observational studies or subgroup analyses have demon- strated an improved survival rate with revascularization compared with medical therapy in patients with CKD and multivessel CAD,189 191 despite the fact that the incidence of periprocedural complications (eg, death, MI, stroke, infec- tion, renal failure) is increased in patients with CKD com- pared with those without renal dysfunction. Some studies have shown that CABG is associated with a greater survival benefit than PCI among patients with severe renal 2.9.3. 