Concomitant NSAID and Anticoagulant Use May Increase Stroke, Bleeding Risk in Afib

Patients with atrial fibrillation who take NSAIDs in addition to oral anticoagulants may have an increased risk for major bleeding and stroke.

Patients with atrial fibrillation taking the anticoagulants dabigatran or warfarin who also used oral nonsteroidal anti-inflammatory drugs (NSAIDs) were significantly more likely to experience major bleeding events and stroke, according to the results of a recent study published in the Journal of the American College of Cardiology.

Data from the RE-LY trial (Randomized Evaluation of Long Term Anticoagulant Therapy With Dabigatran Etexilate; Identifier: NCT00262600), which was an efficacy evaluation that compared dabigatran with warfarin, were re-evaluated with a focus on adverse event rates in trial participants who also used NSAIDs. The rates of bleeding events, strokes, myocardial infarction, and hospitalizations were then compared between groups.

Among the 18,113 participants in RE-LY, 2279 patients (12.6%) used NSAIDs at least once during the trial. Of those individuals who used NSAIDs, rates of bleeding were significantly increased regardless of which anticoagulant was used compared with those who did not use NSAIDs (hazard ratio [HR], 1.68; P <.0001). Furthermore, the rates of stroke (HR, 1.50; P =.007), systemic embolism (HR, 2.43; P =.03), and hospitalization (HR, 1.64; P <.0001) also increased. However, the rates of myocardial infarction (HR, 1.22; P =.40) and all-cause mortality (HR, 1.00; P =.97) were not significantly different. 

The study authors wrote, “The rates of major bleeding, [gastrointestinal] major bleeding, stroke/[systemic embolism], ischemic stroke, and hospitalization when NSAIDs [were] used in combination with [oral anticoagulant] therapy (dabigatran 110 or 150 mg [2 times daily], or warfarin) were significantly elevated compared with patients who did not use NSAIDs.”

They also noted the probable mechanism, suggesting, “the observed bleeding associated with NSAIDs was likely a result of its antiplatelet effects and a reduction in gastric mucosal protection.”

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Based on their findings, the researchers recommended seeking safer alternatives to NSAIDs for patients with atrial fibrillation who receive oral anticoagulant therapy.


Kent AP, Breuckmann M, Fraessdorf M, et al. Concomitant oral anticoagulant and nonsteroidal anti-inflammatory drug therapy in patients with atrial fibrillation [published online July 17, 2018]. J Am Coll Cardiol. 2018;72(3):255-267.