Current and new oral antithrombotics in non-valvular atrial fibrillation: a network meta-analysis of 79 808 patients

Background Antithrombotic therapy reduces stroke, embolism and mortality in patients with atrial fibrillation (AF); however, meta-analyses have focused on pairwise comparisons of treatments. Objective To synthesise the evidence from trials using a multiple treatment comparison methods thereby permitting a broader comparison across multiple therapies. Design, setting, patients Randomised controlled trials in patients with AF of antithrombotics were identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through May 2012. We performed a random-effects model within a Bayesian framework using Markov Chain Monte Carlo simulation to calculate pooled OR and 95% credibility intervals (CrI). We also ranked therapies by their likelihood of leading to the best results for the outcomes. Main outcome measure Multiple endpoints including stroke, embolism, death and bleeding. Results We identified 20 studies with 79 808 patients allocated to 8 treatments: ASA, ASA plus clopidogrel, vitamin K antagonists (VKAs), dabigatran 110 mg, dabigatran 150 mg, rivaroxaban, apixaban or placebo/control. Compared with placebo/control, dabigatran 150 mg was associated with the lowest risk of stroke (OR=0.25, 0.15–0.43), the composite of ischaemic stroke or systemic embolism (OR=0.26, 0.12–0.54) and mortality (OR=0.53, 0.28–0.88). ASA plus clopidogrel was associated with the highest risk of major bleeding (OR=3.65, 1.22–13.56). In simulated comparisons, the novel oral anticoagulants ranked better than VKA or antiplatelet therapies for prevention of stroke, ischaemic stroke or systemic embolism and mortality. Conclusions In this network meta-analysis, novel oral anticoagulants were the most promising treatments to reduce stroke, stroke or systemic embolism, and all-cause mortality in patients with AF.