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Original Investigation
June 19, 2019

Safety and Efficacy of Antithrombotic Strategies in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Network Meta-analysis of Randomized Controlled Trials

Author Affiliations
  • 1Duke Clinical Research Institute, Duke Health, Durham, North Carolina
  • 2Amsterdam UMC Universiteit van Amsterdam, Amsterdam Public Health, Academisch Medisch Centrum, Amsterdam, the Netherlands
  • 3Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massaschusetts
  • 4Mount Sinai Hospital, New York, New York
  • 5Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands
  • 6St Antonius Ziekenhuis, Nieuwegein, the Netherlands
  • 7Universitair Medisch Centrum Groningen, Groningen, the Netherlands
  • 8Ludwig-Maximilians-Universität München, Munich, Germany
  • 9Beth Israel Hospital, Harvard Medical School, Boston, Massaschusetts
JAMA Cardiol. 2019;4(8):747-755. doi:10.1001/jamacardio.2019.1880
Key Points

Question  What is the most appropriate antithrombotic regimen to manage atrial fibrillation and coronary artery disease, in particular with acute coronary syndrome and/or percutaneous coronary intervention, while balancing ischemic and bleeding risk in an understudied high-risk patient population?

Findings  In this network meta-analysis, simultaneous comparisons of multiple antithrombotic strategies were performed for safety and efficacy outcomes in a study involving more than 10 000 participants. The study demonstrated that vitamin K antagonist plus dual antiplatelet therapy should be avoided, whereas the use of a non–vitamin K antagonist oral anticoagulant plus P2Y12 inhibitor, without aspirin, should be the preferred treatment.

Meaning  Meaningful information about antithrombotic regimens may help physicians in their decision making when treating this high-risk group of patients.


Importance  The antithrombotic treatment of patients with atrial fibrillation (AF) and coronary artery disease, in particular with acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), poses a significant treatment dilemma in clinical practice.

Objective  To study the safety and efficacy of different antithrombotic regimens using a network meta-analysis of randomized controlled trials in this population.

Data Sources  PubMed, EMBASE, EBSCO, and Cochrane databases were searched to identify randomized controlled trials comparing antithrombotic regimens.

Study Selection  Four randomized studies were included (n = 10 026; WOEST, PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS).

Data Extraction and Synthesis  The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and network meta-analysis between 4 regimens using a Bayesian random-effects model. A pre hoc statistical analysis plan was written, and the review protocol was registered at PROSPERO. Data were analyzed between November 2018 and February 2019.

Main Outcomes and Measures  The primary safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding; secondary safety outcomes were combined TIMI major and minor bleeding, trial-defined primary bleeding events, intracranial hemorrhage, and hospitalization. The primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE); secondary efficacy outcomes were individual components of MACE.

Results  The overall prevalence of ACS varied from 28% to 61%. The mean age ranged from 70 to 72 years; 20% to 29% of the trial population were women; and most patients were at high risk for thromboembolic and bleeding events. Compared with a regimen of vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT; P2Y12 inhibitor plus aspirin), the odds ratios (ORs) for TIMI major bleeding were 0.58 (95% CI, 0.31-1.08) for VKA plus P2Y12 inhibitor, 0.49 (95% CI, 0.30-0.82) for non-VKA oral anticoagulant (NOAC) plus P2Y12 inhibitor, and 0.70 (95% CI, 0.38-1.23) for NOAC plus DAPT. Compared with VKA plus DAPT, the ORs for MACE were 0.96 (95% CI, 0.60-1.46) for VKA plus P2Y12 inhibitor, 1.02 (95% CI, 0.71-1.47) for NOAC plus P2Y12 inhibitor, and 0.94 (95% CI, 0.60-1.45) for NOAC plus DAPT.

Conclusions and Relevance  A regimen of NOACs plus P2Y12 inhibitor was associated with less bleeding compared with VKAs plus DAPT. Strategies omitting aspirin caused less bleeding, including intracranial bleeding, without significant difference in MACE, compared with strategies including aspirin. Our results support the use of NOAC plus P2Y12 inhibitor as the preferred regimen post–percutaneous coronary intervention for these high-risk patients with AF. A regimen of VKA plus DAPT should generally be avoided.