Adjusted indirect comparison of new oral anticoagulants for stroke prevention in atrial fibrillation

Background: Vit-K antagonists are the therapy of choice to prevent thromboembolic events due to atrial fibrillation since many years. New oral anticoagulants (NOA) showed encouraging results vs. warfarin but there are no data directly comparing different NOA. We performed an adjusted indirect meta-analysis. Methods: Randomized controlled trials (RCTs) were searched. Efficacy end points were the cumulative rate of thomboembolic stroke (TES) and systemic embolism (SE). Main safety end point was the rate of hemorrhagic stroke (HS). Results: Three RCTs (50578 patients) were included. Overall, NOA were comparable to warfarin according to the cumulative risk of TES and SE, as well as for TES alone. NOA were associated with a reduced rate of SE [OR 0.64 (0.44, 0.94], P = 0.02]. Compared to warfarin, NOA were associated with a significantly reduced risk of HS [OR 0.43 (0.34, 0.55), P < 0.001, NNT to avoid a HS 153] and all cause death [OR 0.90 [0.84, 0.96], P = 0.03, NNT to save one fatality 43]. Head to head comparison showed that in terms of cumulative rate of TES/SE, as well as of TES, none of the NOA was significantly superior to the others (all Ps > 0.05). Rivaroxaban showed superiority in the prevention of SE. Dabigatran 150 mg/twice daily was associated with the largest reduction in the risk of HS vs. warfarin and vs. other NOA. Overall mortality was quite comparable across NOA. Conclusions: Overall superiority of NOA over warfarin is largely influenced by the reduction of HS. Dabigatran 150 mg/twice daily seems to have the best risk/benefit profile.