Net clinical benefit of a reduced dose of direct oral anticoagulants in non-valvular atrial fibrillation: a meta-analysis of randomized trials

Objective: To evaluate the net clinical benefit of a reduced dose of direct oral anticoagulants (DOACs) compared to warfarin in nonvalvular atrial fibrillation. Design and method: We searched three electronic databases covering the period until end-February 2021. All-cause death, non-fatal stroke/systemic embolism, and major bleeding events, with or without the inclusion of myocardial infarction, were used to define two different net clinical benefit outcomes. In addition, we evaluated different component outcomes of net clinical benefit as secondary outcomes. Finally, each outcome's risk ratios and 95% Confidence Intervals (CI) were calculated (random-effects model). Results: In the four randomized trials included (n = 29,779 patients), the net clinical benefit - with or without the inclusion of myocardial infarction - of low-dose DOACs, compared to warfarin, was a 12% (95% CI, 7%-16%) or a 10% (95% CI, 5%-13%) reduction of events, respectively. Compared to warfarin, the reduced dose of DOACs decreased death outcomes, major bleeding events, and hemorrhagic stroke, whereas all thrombotic outcomes were not different among the groups. Conclusions: DOACs at low doses present a more favorable net clinical benefit profile than warfarin.