Impact of concomitant antiplatelet therapy on the efficacy and safety of direct oral anticoagulants for acute venous thromboembolism: Systematic review and meta-analysis

Background Direct oral anticoagulants (DOACs) are recommended over vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE). Concomitant antiplatelet therapy may potentiate the antithrombotic effects of DOACs. Objectives We evaluated the impact of concomitant antiplatelet therapy on the efficacy and safety of DOACs. Patients/Methods MEDLINE, EMBASE, and were searched for randomized controlled trials of DOACs for the treatment of acute VTE. The efficacy outcome was symptomatic recurrent VTE and VTE-related death; the primary safety outcome was major bleeding. Results Six randomized controlled trials included 26 924 patients of whom 3550 (13.2%) received concomitant antiplatelet therapy, mainly aspirin (67.7%). Concomitant antiplatelet therapy did not reduce the incidence of recurrent VTE and VTE-related death with any oral anticoagulant (odds ratio [OR] 1.17; 95% confidence interval [CI], 0.92-1.48), with DOACs (OR 1.21; 95% CI, 0.86-1.71), or VKAs alone (OR 1.16; 95% CI, 0.77-1.73). Compared with no antiplatelet therapy, concomitant antiplatelet therapy was associated with a higher risk of major bleeding in patients with any oral anticoagulant (OR 1.79; 95% CI, 1.22-2.63), DOACs (OR 1.89; 95% CI, 1.04-3.44), or VKAs (OR 1.73; 95% CI, 1.16-2.59). In patients receiving concomitant antiplatelet therapy, there were no statistically significant differences in efficacy or safety outcomes with DOACs or VKAs (OR 0.99; 95% CI, 0.64-1.51, and OR 0.68; 95% CI, 0.32-1.45, respectively). Conclusions Concomitant use of antiplatelet therapy with oral anticoagulants does not appear to affect the risk of recurrent VTE and increases the risk of major bleeding.