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Concomitant Use of Direct Oral Anticoagulants with Antiplatelet Agents and the Risk of Major Bleeding in Patients with Nonvalvular Atrial Fibrillation

Patients with nonvalvular atrial fibrillation commonly have comorbidities requiring concurrent use of oral anticoagulants and antiplatelets. There are no real-world data on the comparative safety of concomitant antithrombotic treatments in the era of direct oral anticoagulant (DOACs). Thus, we compared the incidence of intracranial hemorrhage, gastrointestinal bleeding, and other major bleeding between concomitant DOAC-antiplatelet use and concomitant vitamin K antagonist (VKA)-antiplatelet use in patients with nonvalvular atrial fibrillation.


Using computerized health care databases from Québec, we conducted a cohort study among patients newly diagnosed with nonvalvular atrial fibrillation between January 2011 and March 2014. Cox proportional hazards models yielded hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for disease risk score, of the study outcomes comparing current concomitant use of DOACs with ≥1 antiplatelet vs current concomitant use of VKAs with ≥1 antiplatelet.


A total of 5301 patients initiated concomitant DOAC-antiplatelet use, while 9106 patients initiated concomitant VKA-antiplatelet use. During a median follow-up of 1.6 months, concomitant DOAC-antiplatelet use was associated with a similar risk of gastrointestinal bleeding (HR 1.08; 95% CI, 0.81-1.45), but with a decreased risk of intracranial hemorrhage (HR 0.46; 95% CI, 0.24-0.91) and other major bleeding (HR 0.68; 95% CI, 0.51-0.91) compared with concomitant VKA-antiplatelet use.


Concomitant DOAC-antiplatelet use was associated with a similar risk of gastrointestinal bleeding, and a lower risk of intracranial hemorrhage and other major bleeding than concomitant VKA-antiplatelet use. These findings could inform physician decision-making in patients requiring concomitant treatment with oral anticoagulants and antiplatelets.

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-Antonios Douros, MD, PhD, Christel Renoux, MD, PhD, Hui Yin, MSc, Kristian B. Filion, PhD, Samy Suissa, PhD, Laurent Azoulay, PhD

This article originally appeared in the February issue of The American Journal of Medicine.

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