Non-vitamin K oral anticoagulants in nonvalvular atrial fibrillation: a network meta-analysis

Objectives. We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) including the comparison of non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin for patients with atrial fibrillation (AF). Design. Network meta-analysis. Two authors independently extracted data. All authors evaluated overall confidence in the evidence. Results. Eighteen RCTs included in our review, a total of 78,796 patients with AF, with sample sizes from 90 to 21,105 patients. Apixaban 5?mg (OR: 0.79, 95% CI: 0.66 to 0.95), dabigatran 110?mg (0.91, 0.74–1.12), dabigatran 150?mg (0.66, 0.53–0.82), edoxaban 60?mg (0.87, 0.74–1.02), and rivaroxaban 20?mg (0.88, 0.74–1.03) reduced the risk of stroke or systemic embolism compared with warfarin. Dabigatran 150?mg had the highest P-score for reducing stroke or systemic embolic events. The risk of haemorhagic stroke and all-cause mortality was lower with all NOACs than with warfarin. Apixaban 5?mg (0.69, 0.60–0.80), dabigatran 110?mg (0.80, 0.69–0.93), dabigatran 150?mg (0.93, 0.80–1.08), edoxaban 30?mg (0.46, 0.40–0.54), and edoxaban 60?mg (0.78, 0.69–0.90) reduced the risk of major bleeding compared with warfarin. Edoxaban 30?mg had the highest P-score for reducing major bleeding. The plots of P-scores rank showed that apixaban offered the most favorable balance of efficacy and safety. Conclusions. This study adds an attempt for treatment ranking of both efficacy and safety outcomes. Future trials comparing directly NOACs are needed in order to provide conclusive proofs for these results and not only circumstantial evidence offered by a network meta-analysis.