Extracranial arterial and venous thromboembolism in patients with atrial fibrillation: A meta-analysis of randomized controlled trials

BACKGROUND Thromboembolism prevention is central to atrial fibrillation (AF) management. Randomized controlled trials (RCTs) have primarily focused on stroke prevention. Detailed analyses of extracranial thromboembolic events, particularly in patients with low dose nonvitamin K antagonist oral anticoagulants (NOACs), are scarce. OBJECTIVE The purpose of this study was to assess efficacy of NOACs in prevention of extracranial arterial and venous thromboembolism. METHODS We searched PubMed, CENTRAL, and CINAHL through April 2016 for phase III RCTs of NOACs in patients with AF. Information regarding systemic embolism (SE), pulmonary embolism (PE), and deep vein thrombosis (DVT) was retrieved and compared by risk ratio (RR) and 95% confidence interval (CI) with a fixed-effects model. A network with additional RCTs involving antiplatelet agents was constructed. The surface under the cumulative ranking curve (SUCRA) of each treatment was calculated for assessing the best treatment in the network meta-analysis. RESULTS Among 72,963 patients with AF from 5 RCTs, relative to warfarin, standard dose NOACs were associated with a lower risk of SE (RR 0.71, 95% CI 0.52-0.99) and similar risks of PE and DVT (RR 0.95, 95% CI 0.72-1.35; and RR 0.83, 95% CI 0.56-1.24, respectively). Compared with warfarin, risks of SE, PE, and DVT with low dose NOACs were similar. In network meta-analyses, standard dose NOACs were associated with the largest SUCRA for prevention of SE and PE. CONCLUSION In patients with AF, standard dose NOACs were the most efficacious treatment in preventing SE, whereas both dose regimens of NOACs were reasonable alternatives to warfarin in preventing venous thromboembolism.