A systematic review of network meta-analyses among patients with nonvalvular atrial fibrillation: A comparison of efficacy and safety following treatment with direct oral anticoagulants

Background: Direct oral anticoagulants (DOACs) are indicated for the prevention of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation. While no head-to-head randomized controlled trials (RCTs) exist that evaluate the efficacy and safety of DOACs, network meta-analyses (NMAs) based mainly on RCTs for each DOAC and using various methodologies have been published. This systematic literature review summarizes the evidence on stroke/SE bleeding events, mortality, and other adverse events from NMAs that reported indirect comparisons of DOACs. Methods: Searches were conducted in PubMed, Embase, and the Cochrane Database of Systematic Reviews to identify NMAs published between January 2010 and March 2017 that compared vitamin K antagonists or DOACs using RCT data. Comparisons on stroke/SE and major bleeding (MB), as well as secondary outcomes, for DOAC versus DOAC comparisons were extracted and summarized using apixaban as the reference. Results: Twenty-two NMAs were included in the final summary: All assessed MB; 15 assessed stroke/SE. No statistically significant differences were observed for apixaban compared with any DOAC in the 15 NMAs that assessed stroke/SE. Apixaban was associated with a lower risk for MB compared with rivaroxaban in 16 of 20 NMAs and dabigatran 150 mg in 13 of 16 NMAs. Four of 6 NMAs showed lower risk for GI bleeding for apixaban compared with rivaroxaban and dabigatran 150 mg; however, this outcome was not assessed by most NMAs. Conclusion: This systematic literature review of NMAs showed varying levels of bleeding risk among DOACs, with apixaban generally having a lower risk than rivaroxaban and dabigatran 150 mg. (c) 2018 The Authors. Published by Elsevier B.V.