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Review
. 2020 May 1;5(5):582-589.
doi: 10.1001/jamacardio.2019.6175.

Optimal Antithrombotic Regimens for Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: An Updated Network Meta-analysis

Renato D Lopes  1 , Hwanhee Hong  2   3 , Ralf E Harskamp  4 , Deepak L Bhatt  5 , Roxana Mehran  6   7 , Christopher P Cannon  5 , Christopher B Granger  1 , Freek W A Verheugt  8 , Jianghao Li  1 , Jurriën M Ten Berg  9   10 , Nikolaus Sarafoff  11 , Pascal Vranckx  12 , Andreas Goette  13 , C Michael Gibson  14 , John H Alexander  1
Affiliations
Review

Optimal Antithrombotic Regimens for Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: An Updated Network Meta-analysis

Renato D Lopes et al. JAMA Cardiol. .

Abstract

Importance: Antithrombotic treatment in patients with atrial fibrillation (AF) and percutaneous coronary intervention (PCI) presents a balancing act with regard to bleeding and ischemic risks.

Objectives: To evaluate the safety and efficacy of 4 antithrombotic regimens by conducting an up-to-date network meta-analysis and to identify the optimal treatment for patients with AF undergoing PCI.

Data sources: Online computerized database (MEDLINE).

Study selection: Five randomized studies were included (N = 11 542; WOEST, PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, ENTRUST-AF PCI).

Data extraction and synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used in this network meta-analysis, in which bayesian random-effects models were applied. The data were analyzed from September 9 to 29, 2019.

Main outcomes and measures: The primary safety outcome was thrombolysis in myocardial infarction (TIMI) major bleeding and the primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE).

Results: The total number of participants included in the study was 11 532. The mean age of the participants ranged from 70 to 72 years, 69% to 83% were male, 20% to 26% were female, and the participants were predominantly white (>90%). Compared with vitamin K antagonists (VKA) plus dual antiplatelet therapy (DAPT) (reference), the odds ratios (ORs) (95% credible intervals) for TIMI major bleeding were 0.57 (0.31-1.00) for VKA plus P2Y12 inhibitor, 0.69 (0.40-1.16) for non-VKA oral anticoagulant (NOAC) plus DAPT, and 0.52 (0.35-0.79) for NOAC plus P2Y12 inhibitor. For MACE, using VKA plus DAPT as reference, the ORs (95% credible intervals) were 0.97 (0.64-1.42) for VKA plus P2Y12 inhibitor, 0.95 (0.64-1.39) for NOAC plus DAPT, and 1.03 (0.77-1.38) for NOAC plus P2Y12 inhibitor.

Conclusions and relevance: The findings of this study suggest that an antithrombotic regimen of VKA plus DAPT should generally be avoided, because regimens in which aspirin is discontinued may lead to lower bleeding risk and no difference in antithrombotic effectiveness. The use of a NOAC plus a P2Y12 inhibitor without aspirin may be the most favorable treatment option and the preferred antithrombotic regimen for most patients with AF undergoing PCI.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Lopes reported receiving consulting fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo, Merck, and Portola Pharmaceuticals; and grants and consulting fees from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi outside the submitted work. Dr Harskamp reported receiving grants from the Dutch Research Council outside the submitted work. Dr Bhatt reported receiving grants from Amarin Corporation, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi, The Medicines Company, PLx Pharma, Roche, Pfizer, Forest Laboratories/AstraZeneca, Ischemix, Amgen, Eli Lilly and Company, Chiesi, Ironwood Pharmaceuticals, Abbott Laboratories, Regeneron Pharmaceuticals, Idorsia, Synaptic Pharma Ltd, Fractyl, and Afimmune; consulting fees from FlowCo Inc, Takeda, Medscape Cardiology, Regado Biosciences, Boston VA Research Institute, Clinical Cardiology, Veterans Affairs, St. Jude Medical (now Abbott), Biotronik, Cardax, Boston Scientific, Merck, Svelte Pharma, Novo Nordisk, Cereno Scientific, and Cardiovascular Systems Inc; personal fees from Harvard Clinical Research Institute (now Baim Institute for Clinical Research), Duke Clinical Research Institute, Mayo Clinic, Population Health Research Institute, Belvoir Publications, Slack Publications, WebMD, Elsevier, HMP Global, Journal of the American College of Cardiology, Cleveland Clinic, Mount Sinai School of Medicine, TobeSoft, Bayer, Medtelligence/ReachMD, CSL Behring, and Ferring Pharmaceuticals; personal fees, travel reimbursement, and consulting fees from the American College of Cardiology; personal fees and nonfinancial support from the Society of Cardiovascular Patient Care; nonfinancial support from the American Heart Association; grants and consulting fees from PhaseBio; and personal fees and consulting fees from Boehringer Ingelheim outside the submitted work. Dr Mehran reported receiving grants from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb, CSL Behring, Daiichi Sankyo Inc, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; personal fees from Abbott Laboratories, Boston Scientific, Medscape/WebMD, Siemens Medical Solutions, PLx Opco Inc/dba PLx Pharma Inc, Roivant Sciences, Sanofi, Medtelligence (Janssen Scientific Affairs), Janssen Scientific Affairs, American College of Cardiology, and American Medical Association; consulting fees from Abbott Laboratories, Abiomed, The Medicines Company, Spectranetics/Philips/Volcano Corp, Bristol-Myers Squibb, Watermark Research Partners, Claret Medical, and Elixir Medical; and nonfinancial support and consulting fees from Regeneron Pharmaceuticals outside the submitted work. Dr Cannon reported receiving grants and personal fees from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen, and Pfizer during the conduct of the study; grants from Amgen and Merck; and personal fees from Aegerion, Alnylam, Amarin Corporation, Amgen, Applied Therapeutics, Ascendia, Corvidia, HLS Therapeutics, Innovent, Kowa, and Sanofi outside the submitted work. Dr Granger reported receiving personal fees from Bayer and Boston Scientific; grants and personal fees from Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, and Pfizer; and grants from Daiichi Sankyo during the conduct of the study; personal fees from Abbvie, Espero, Medscape, Medtronic, Merck, National Institutes of Health, Novo Nordisk, Roche, Eli Lilly and Company, Gilead Sciences, Hoffmann-La Roche, Sirtex, Verseon, Rho Pharmaceuticals, and CeleCor Therapeutics; grants from Akros, US Food and Drug Administration, GlaxoSmithKline, Medtronic Foundation, and Apple; and grants and personal fees from AstraZeneca, Novartis, Armetheon, and The Medicines Company outside the submitted work. Dr Verheugt reported receiving personal fees from Bayer HealthCare, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo during the conduct of the study. Dr Sarafoff reported receiving personal fees from Boehringer Ingelheim, and nonfinancial support from Bayer and Pfizer outside the submitted work. Dr Vranckx reported receiving personal fees from Daiichi Sankyo during the conduct of the study; and personal fees from Bayer, Behring CLS, and AstraZeneca outside the submitted work. Dr Goette reported receiving personal fees from Daiichi Sankyo, Boston Scientific, Boehringer Ingelheim, Bayer, AstraZeneca, Medtronic, Omeicos, and Bristol-Myers Squibb/Pfizer outside the submitted work. Dr Gibson reported receiving grants and personal fees from Bayer, Janssen Pharmaceuticals, Johnson & Johnson Corporation, and Portola Pharmaceuticals; and grants from Bristol-Myers Squibb during the conduct of the study; grants and personal fees from Angel Medical Corporation and CSL Behring; personal fees from The Medicines Company, Boston Clinical Research Institute, Cardiovascular Research Foundation, Eli Lilly and Company, Gilead Sciences, Novo Nordisk, WebMD, UpToDate in Cardiovascular Medicine, Amarin Corporation, Amgen, Boehringer Ingelheim, Chiesi, Merck, PharmaMar, Sanofi, Somahlution, St. Francis Hospital, Verreseon Corporation, Boston Scientific, Duke Clinical Research Institute, Impact Bio, Ltd, MedImmune, Medtelligence, Microport, and PERT Consortium; consulting fees from nference; nonfinancial support from Baim Institute; grants from SCAD Alliance; and personal fees from GE Healthcare, Caladrius Bioscience, CeleCor Therapeutics, and Thrombolytic Science outside the submitted work. Dr Alexander reported receiving grants from AstraZeneca, Boehringer Ingelheim, CryoLife, US Food & Drug Administration, National Institutes of Health, Sanofi, and Volumetrix; and personal fees from AbbVie; grants and personal fees from Bristol-Myers Squibb, CSL Behring, Novo Nordisk, Pfizer, Portola Pharmaceuticals, Quantum Genomics, Teikoku Pharmaceuticals, VA Cooperative Studies Program, and Zafgen outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Network of 4 Antithrombotic Treatment Regimens
The nodes represent the antithrombotic treatment regimens that were compared, and the edges represent the observed direct comparisons in the included randomized clinical trials. The size of nodes is proportional to the number of patients assigned to the treatment regimen and the thickness of edges is proportional to the sample size of each study. AF indicates atrial fibrillation; DAPT, dual antiplatelet therapy; NOAC, non-VKA oral anticoagulant; PCI, percutaneous coronary intervention; VKA, vitamin K antagonists.
Figure 2.
Figure 2.. Forest Plots for Safety and Efficacy Outcomes
The safety outcomes assessed were thrombolysis in myocardial infarction (TIMI) major bleeding, TIMI major or minor bleeding, trial-defined primary safety outcome, and intracranial hemorrhage. A total of 11 430 patients were included in the network meta-analyses for all safety outcomes. The efficacy outcomes assessed were all-cause death, myocardial infarction, stroke, and stent thrombosis. A total of 11 501 patients were included in the network meta-analyses for all efficacy outcomes. Odds ratios and 95% credible intervals compared with vitamin K antagonist plus dual antiplatelet therapy (VKA+DAPT) (reference) were plotted for all outcomes. NOAC indicates non-VKA oral anticoagulant.
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