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Meta-analysis and adjusted indirect comparison of direct oral anticoagulants in prevention of acute limb ischemia in patients with atrial fibrillation

Abstract Background: Direct oral anticoagulants are being presented as alternatives to warfarin for preventing stroke in patients with atrial fibrillation. Yet direct comparative trials between these agents in prevention of acute limb ischemia (ALI) are unavailable so far. Objective: To conduct an adjusted indirect comparison meta-analysis between direct oral agents for prevention of acute limb ischemia in atrial fibrillation. Methods: We conducted a systematic literature review searching electronic databases (MEDLINE and Embase) and the Cochrane Library from January 1990 through November 2014. Two blinded investigators reviewed all potentially relevant articles in a parallel manner by using a priori defined criteria. To assess the long-term efficacy and safety of these agents, only randomized clinical trials (RCTs) with follow-up durations of >1 year were included. The primary efficacy outcome was the end point of acute limb ischemia and/or extremity embolism. Results: A total of 44,563 patients from three RCTs met criteria for inclusion. Patients randomized to direct oral anticoagulants had a non-significant decreased risk for acute limb ischemia (risk ratio [RR]: 0.57, 95% confidence interval [CI]: 0.26–1.2). In the analysis between agents, however, rivaroxaban significantly lowered the risk of ALI compared to warfarin (RR: 0.23, 95% CI: 0.064–0.82), apixaban (RR: 0.26, 95% CI: 0.081–0.83), and dabigatran (RR: 0.24, 95% CI: 0.077–0.83). Conclusions: Significant differences in prevention of acute limb ischemia may exist between oral anticoagulant agents in patients with atrial fibrillation. Rivaroxaban lowers the risk of limb embolism versus warfarin, apixaban and dabigatran.