Systematic review and adjusted indirect comparison meta-analysis of oral anticoagulants in atrial fibrillation.

BACKGROUND Oral anticoagulants such as apixaban, dabigatran, and rivaroxaban are alternatives to warfarin for preventing events in patients with atrial fibrillation. Direct comparative studies between agents are unavailable. Our objective was to conduct an adjusted indirect comparison meta-analysis between new oral agents in atrial fibrillation. METHODS AND RESULTS We searched MEDLINE and Cochrane Central through February 2012 for randomized, controlled trials in patients with atrial fibrillation evaluating apixaban, dabigatran, or rivaroxaban versus warfarin. For dabigatran, only data from the Food and Drug Administration-approved dose were included. Outcomes included the composite of stroke or systemic embolism, any stroke, and major bleeding among, others. Outcomes were initially pooled using standard random-effects methods, producing risk ratio and 95% confidence intervals. Adjusted indirect comparisons using these pooled estimates were then performed. A total of 44 733 patients from 4 studies were analyzed. Most analyses yielded no differences between agents. Dabigatran lowered risk of composite outcome (risk ratio, 0.75; 95% confidence interval, 0.57-1.00), ischemic stroke (0.67; 0.48-0.93), and hemorrhagic stroke (0.45; 0.45-0.99) versus rivaroxaban. No differences in all strokes or mortality were seen. Apixaban lowered the risk of major bleeding (0.74; 0.60-0.91) and gastrointestinal bleeding (0.58; 0.41-0.82) versus dabigatran and major bleeding versus rivaroxaban (0.68; 0.55-0.83), but increased systemic emboli versus rivaroxaban (3.86; 1.17-12.75). CONCLUSIONS Significant differences in efficacy and safety parameters may exist between oral anticoagulant agents in patients with atrial fibrillation. Apixaban lowers the risk of major and gastrointestinal bleeding versus dabigatran and rivaroxaban. Dabigatran lowers the composite of stroke or systemic emboli, and ischemic stroke versus rivaroxaban. Head-to-head clinical trials are required to confirm these findings.