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 Clinicaltrial.gov 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.