2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable …
2016; Lippincott Williams & Wilkins; Volume: 134; Issue: 10 Linguagem: Inglês
10.1161/cir.0000000000000404
ISSN1524-4539
AutoresGlenn N. Levine, Eric Bates, John A. Bittl, Ralph G. Brindis, Stephan D. Fihn, Lee A. Fleisher, Christopher B. Granger, Richard A. Lange, Michael J. Mack, Laura Mauri, Roxana Mehran, Debabrata Mukherjee, L. Kristin Newby, Patrick T. O’Gara, Marc S. Sabatine, Peter K. Smith, Sidney C. Smith,
Tópico(s)Acute Myocardial Infarction Research
ResumoHomeCirculationVol. 134, No. 102016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessResearch ArticlePDF/EPUB2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery Glenn N. Levine, MD, FACC, FAHA, Chair, Eric R. Bates, MD, FACC, FAHA, FSCAI, John A. Bittl, MD, FACC, Ralph G. Brindis, MD, MPH, MACC, FAHA, Stephan D. Fihn, MD, MPH, Lee A. Fleisher, MD, FACC, FAHA, Christopher B. Granger, MD, FACC, FAHA, Richard A. Lange, MD, MBA, FACC, Michael J. Mack, MD, FACC, Laura Mauri, MD, MSc, FACC, FAHA, FSCAI, Roxana Mehran, MD, FACC, FAHA, FSCAI, Debabrata Mukherjee, MD, FACC, FAHA, FSCAI, L. Kristin Newby, MD, MHS, FACC, FAHA, Patrick T. O’Gara, MD, FACC, FAHA, Marc S. Sabatine, MD, MPH, FACC, FAHA, Peter K. Smith, MD, FACC and Sidney C. SmithJr, MD, FACC, FAHA Glenn N. LevineGlenn N. Levine *, †, ‡, §, ‖, ¶, # Search for more papers by this author , Eric R. BatesEric R. Bates *, †, ‡, §, ‖, ¶, # Search for more papers by this author , John A. BittlJohn A. Bittl *, †, ‡, §, ‖, ¶, # Search for more papers by this author , Ralph G. BrindisRalph G. Brindis *, †, ‡, §, ‖, ¶, # Search for more papers by this author , Stephan D. FihnStephan D. Fihn *, †, ‡, §, ‖, ¶, # Search for more papers by this author , Lee A. FleisherLee A. Fleisher *, †, ‡, §, ‖, ¶, # Search for more papers by this author , Christopher B. GrangerChristopher B. Granger *, †, ‡, §, ‖, ¶, # Search for more papers by this author , Richard A. LangeRichard A. Lange *, †, ‡, §, ‖, ¶, # Search for more papers by this author , Michael J. MackMichael J. Mack *, †, ‡, §, ‖, ¶, # Search for more papers by this author , Laura MauriLaura Mauri *, †, ‡, §, ‖, ¶, # Search for more papers by this author , Roxana MehranRoxana Mehran *, †, ‡, §, ‖, ¶, # Search for more papers by this author , Debabrata MukherjeeDebabrata Mukherjee *, †, ‡, §, ‖, ¶, # Search for more papers by this author , L. Kristin NewbyL. Kristin Newby *, †, ‡, §, ‖, ¶, # Search for more papers by this author , Patrick T. O’GaraPatrick T. O’Gara *, †, ‡, §, ‖, ¶, # Search for more papers by this author , Marc S. SabatineMarc S. Sabatine *, †, ‡, §, ‖, ¶, # Search for more papers by this author , Peter K. SmithPeter K. Smith *, †, ‡, §, ‖, ¶, # Search for more papers by this author and Sidney C. SmithJrSidney C. SmithJr *, †, ‡, §, ‖, ¶, # Search for more papers by this author Originally published29 Mar 2016https://doi.org/10.1161/CIR.0000000000000404Circulation. 2016;134:e123–e155is corrected byCorrection to: 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guidelineon Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac SurgeryOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2016: Previous Version 1 Table of ContentsPreamble e124Introduction e1251.1. Methodology and Evidence Review e1261.1. Organization of the Writing Group e1271.3. Review and Approval e127Critical Questions and Systematic Review Findings e1272.1. Critical Questions on Duration of DAPT e1272.2. Studies of Shorter-Duration DAPT After Stent Implantation e1272.3. Studies of Longer-Duration DAPT After Stent Implantation e1282.4. Other Studies Relevant to DAPT >1 Year After MI e1282.5. Prolonged/Extended DAPT and Mortality Rate e128Overriding Concepts and Recommendations for DAPT and Duration of Therapy e1293.1. General Overriding Concepts e1293.2. Factors Associated With Increased Ischemic and Bleeding Risk e1293.3. Specific P2Y12 Inhibitors: Recommendations e1313.4. Platelet Function Testing, Genetic Testing, and Switching of P2Y12 Inhibitors e1313.5. Proton Pump Inhibitors and DAPT e1323.6. Aspirin Dosing in Patients Treated With DAPT: Recommendation e1323.7. Triple Therapy (Aspirin, P2Y12 Inhibitor, and Oral Anticoagulant) e132Percutaneous Coronary Intervention e1334.1. Duration of DAPT in Patients With SIHD Treated With PCI: Recommendations e1334.2. Duration of DAPT in Patients With ACS Treated With PCI: Recommendations e1334.3. Duration of DAPT in Patients With SIHD and ACS Treated with PCI e134Recommendations for Duration of DAPT in Patients Undergoing CABG e134Recommendations for Duration of DAPT in Patients With SIHD e135Acute Coronary Syndrome (NSTE-ACS and STEMI) e1377.1. Duration of DAPT in Patients With ACS Treated With Medical Therapy Alone (Without Revascularization or Fibrinolytic Therapy): Recommendations e1377.2. Duration of DAPT in Patients With STEMI Treated With Fibrinolytic Therapy: Recommendations e1387.3. Duration of DAPT in Patients With ACS Treated With PCI: Recommendations e1387.4. Duration of DAPT in Patients With ACS Treated With CABG: Recommendation e1387.5. Duration of DAPT in Patients With ACS e138Perioperative Management–Timing of Elective Noncardiac Surgery in Patients Treated With PCI and DAPT: Recommendations e140References e143Appendix 1. Author Relationships With Industry and Other Entities (Relevant) e149Appendix 2. Reviewer Relationships With Industry and Other Entities (Relevant) e151PreambleIncorporation of new study results, medications, or devices that merit modification of existing clinical practice guideline recommendations, or the addition of new recommendations, is critical to ensuring that guidelines reflect current knowledge, available treatment options, and optimum medical care. To keep pace with evolving evidence, the American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Clinical Practice Guidelines (“Task Force”) has issued this focused update to revise existing guideline recommendations on the basis of recently published study data. This update has been subject to rigorous, multilevel review and approval, similar to the full guidelines. For specific focused update criteria and additional methodological details, please see the ACC/AHA guideline methodology manual.1ModernizationProcesses have evolved over time in response to published reports from the Institute of Medicine2,3 and ACC/AHA mandates,4–7 leading to adoption of a “knowledge byte” format. This process entails delineation of a recommendation addressing a specific clinical question, followed by concise text (ideally 1 year prior who have since remained free of recurrent ACS are considered to have transitioned to stable ischemic heart disease (SIHD) and are addressed in the section on SIHD. Issues and recommendations with regard to P2Y12 inhibitor “pretreatment,” “preloading,” and loading are beyond the scope of this document but are addressed in other guidelines.9,14,29This focused update is designed to function both as a standalone document and to serve as an update to the relevant sections on duration of DAPT in the 6 clinical practice guidelines, replacing relevant text, figures, and recommendations. Thus, by necessity, there is some redundancy in different sections of this document. When possible, the “knowledge byte” format was used for recommendations. In some cases, the complexity of this document required a modification of the knowledge byte format, with several interrelated recommendations grouped together, followed by concise associated text ( 12 (18–48) months of DAPT result in differences in mortality rate, decreased MACE, decreased stent thrombosis, and/or increased bleeding?Q3: In post-MI (NSTEMI or STEMI) patients who are clinically stable and >12 months past their event, does continued DAPT, compared with aspirin monotherapy, result in differences in mortality rate, decreased nonfatal MI, decreased MACE, and/or increased bleeding?ACS indicates acute coronary syndrome; DAPT, dual antiplatelet therapy; DES, drug-eluting stents; MACE, major adverse cardiac events; MI, myocardial infarction; NSTEMI, non–ST-elevation myocardial infarction; PICOTS, population, intervention, comparison, outcome, timing, and setting; SIHD, stable ischemic heart disease; and STEMI, ST-elevation myocardial infarction.2.2. Studies of Shorter-Duration DAPT After Stent ImplantationFive RCTs of patients treated with elective DES implantation have compared shorter-duration (3 to 6 months) DAPT with 12 months of DAPT17–21 (Data Supplement 1). The trials primarily enrolled low-risk (non-ACS) patients, with only a small proportion having had a recent MI. The main endpoints of these noninferiority trials were composite ischemic events (or net composite events) and stent thrombosis. These studies, as well as several meta-analyses34–37 and an analysis by the ERC,30 did not find any increased risk of stent thrombosis with shorter-duration DAPT. A shorter duration of DAPT results in fewer bleeding complications.30,34–36 Shorter-duration DAPT may be most reasonable in patients currently being treated with “newer-generation” (eg, everolimus- or zotarolimus-eluting) DES, which are associated with lower stent thrombosis and MI rates than those of “first-generation” (eg, sirolimus- and paclitaxel-eluting) DES, which are rarely, if ever, used in current clinical practice.16,36,382.3. Studies of Longer-Duration DAPT After Stent ImplantationSix RCTs, consisting predominantly of patients treated with elective DES implantation, compared prolonged DAPT (total therapy duration: 18 to 48 months) with 6 to 12 months of DAPT to determine whether extended therapy reduces late and very late stent thrombosis and prevents ischemic events associated with disease progression and plaque rupture at other nonstented sites16,22–27 (Data Supplement 2). In the Dual Antiplatelet Therapy study—the largest of these trials—patients who had undergone DES implantation, had been treated with DAPT for 12 months, and were without ischemic or bleeding events during this period were randomized to an additional 18 months of DAPT or to aspirin monotherapy.16 Extended DAPT resulted in a 0.7% absolute reduction in very late stent thrombosis, a 2.0% absolute reduction in MI, a 1.6% absolute reduction in major adverse cardiac events (MACE), and a 0.9% absolute increase in moderate or severe bleeding. In the subgroup of patients treated with everolimus-eluting stents—currently the most commonly used stent—extended DAPT resulted in a 0.4% absolute reduction in stent thrombosis, a 1.1% absolute reduction in MI, and a 1.2% absolute increase in moderate/severe bleeding.39Taken as a whole, studies of longer-duration (“prolonged” or “extended”) DAPT16,22–27 for an additional 18 to 36 months after DES found an absolute decrease in late stent thrombosis and ischemic complications of ≈1% to 2% and an absolute increase in bleeding complications of ≈1% (Data Supplements 2 and 3). A weighted risk-benefit analysis by the ERC of studies of patients treated with DES found 6 fewer MIs and 3 fewer stent thromboses but 5 additional major bleeds per 1000 patients treated with prolonged DAPT per year.302.4. Other Studies Relevant to DAPT >1 Year After MIThe CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial randomized patients with established atherosclerosis or at high risk of clinical atherosclerotic disease to either DAPT (with clopidogrel) or aspirin monotherapy; with DAPT, no significant reduction was found in ischemic effects at a median follow-up of 28 months, but there was a 0.4% absolute increase in severe bleeding.40 A post hoc analysis of patients enrolled in the study with prior MI found a 1.7% absolute decrease in the composite endpoint of cardiovascular death, MI, or stroke events with DAPT, with no benefit in those with CAD without prior MI.40,41Patients in the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin—Thrombolysis In Myocardial Infarction 54) trial were randomized 1 to 3 years after MI with additional high-risk features to either DAPT (with ticagrelor 60 mg or 90 mg twice daily) or continued aspirin monotherapy.28 After a mean of 33 months of therapy, DAPT, when compared with aspirin monotherapy, resulted in a 1.2% to 1.3% absolute reduction in the primary composite endpoint of cardiovascular death, MI, or stroke and a 1.2% to 1.5% absolute increase in major bleeding, with no excess in fatal bleeding or intracranial hemorrhage. In subgroup analysis, the greatest reduction in ischemic events with prolonged DAPT was in patients in whom P2Y12 inhibitor therapy either had not been discontinued or had been discontinued for ≤30 days (absolute reduction in MACE: 1.9% to 2.5%). No benefit was seen in patients in whom P2Y12 inhibitor therapy had been discontinued >1 year before enrollment in the study.42In the Dual Antiplatelet Therapy study, the benefit/risk ratio for prolonged DAPT was more favorable for those presenting with MI than those with SIHD.43 In an analysis of patients with a history of prior MI enrolled in 6 RCTs of extended/prolonged DAPT, extended DAPT significantly decreased the absolute risk of MACE by 1.1% and significantly increased the absolute risk of major bleeding by 0.8%.44Taken as a whole, trials of prolonged or extended DAPT suggest that the benefit/risk ratio of prolonged DAPT may be more favorable for those with prior MI, with an absolute decrease in ischemic events of ≈1% to 3% at the cost of an absolute increase in bleeding events of ≈1% over the course of several years of prolonged or extended therapy (median durations of therapy: 18 to 33 months) (Data Supplements 3 and 4). This appears biologically plausible because patients with prior MI (usually mediated by plaque rupture) may be at greater risk for future plaque rupture than those without prior MI.37,40,412.5. Prolonged/Extended DAPT and Mortality RateAn unexpected finding in the Dual Antiplatelet Therapy study16 was a borderline-significant increase in overall mortality rate (0.5% absolute increase) with 30 months of DAPT versus 12 months of DAPT in DES-treated patients, which was due to significantly increased deaths from noncardiovascular causes (most commonly cancer), with no increase in cardiovascular deaths, and no significant increase in fatal bleeding.45 Five subsequent meta-analyses35–37,46,47 restricted to RCTs of studies enrolling patients treated with predominantly newer generation DES, published prior to the presentation of the OPTIDUAL (Optimal Dual Antiplatelet Therapy) trial, found numerically36,47 or statistically35,37,46 significant increased risk of all-cause (though not cardiovascular) death associated with prolonged duration of DAPT (Data Supplements 3 and 4).In contrast, a meta-analysis that combined studies of DAPT duration after stent implantation with studies of DAPT duration for other indications48 and an analysis of 6 trials restricted to post-MI patients treated with DAPT44 found no increase in cardiovascular or noncardiovascular mortality rate associated with prolonged DAPT (Data Supplement 3). A US Food and Drug Administration drug safety communication, based on an evaluation of long-term clinical trials of patients with cardiovascular disease or stroke treated with clopidogrel, concluded that long-term clopidogrel treatment did not increase the risk of all-cause death or cancer-related death.49 The primary analysis by the ERC of 11 RCTs (including OPTIDUAL) compared use of DAPT for 18 to 48 months with use of DAPT for 6 to 12 months in patients who had received predominantly newer-generation DES and found no statistically significant difference in all-cause mortality rate.30A majority of writing group members believe the data as a whole do not seem to suggest prolonged DAPT results in increased mortality.3. Overriding Concepts and Recommendations for DAPT and Duration of Therapy3.1. General Overriding ConceptsOverriding concepts and relevant recommendations for DAPT and duration of therapy are summarized in Table 3. Intensification of antiplatelet therapy, with the addition of a P2Y12 inhibitor to aspirin monotherapy, necessitates a fundamental tradeoff between decreasing ischemic risk and increasing bleeding risk.40,41,50–52 Similarly, longer compared with shorter duration of DAPT generally results in decreased ischemic risk at the expense of increased bleeding risk.16,24,28,30,46 Use of more potent P2Y12 inhibitors (ticagrelor or prasugrel) in place of clopidogrel also results in decreased ischemic risk and increased bleeding risk.53–55Table 3. Overriding Concepts and Updated Recommendations for DAPT and DurationIntensifi
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