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.