Comparative Effectiveness of Interventions for Stroke Prevention in Atrial Fibrillation: A Network Meta‐Analysis

BACKGROUND: The goal of this study was to compare the safety and effectiveness of individual antiembolic interventions in nonvalvular atrial fibrillation (AF): novel oral anticoagulants (NOACs) (apixaban, dabigatran, edoxaban, and rivaroxaban); vitamin K antagonists (VKA); aspirin; and the Watchman device. METHODS AND RESULTS: A network meta‐analysis of randomized, clinical trials (RCTs) was performed. RCTs that included patients with prosthetic cardiac valves or mitral stenosis, mean or median follow‐up <6 months, <200 participants, without published report in English language, and NOAC phase II studies were excluded. The placebo/control arm received either placebo or no treatment. The primary efficacy outcome was the combination of stroke (of any type) and systemic embolism. All‐cause mortality served as a secondary efficacy outcome. The primary safety outcome was the combination of major extracranial bleeding and intracranial hemorrhage. A total of 21 RCTs (96 017 nonvalvular AF patients; median age, 72 years; 65% males; median follow‐up, 1.7 years) were included. In comparison to placebo/control, use of aspirin (odds ratio [OR], 0.75 [95% CI, 0.60–0.95]), VKA (0.38 [0.29–0.49]), apixaban (0.31 [0.22–0.45]), dabigatran (0.29 [0.20–0.43]), edoxaban (0.38 [0.26–0.54]), rivaroxaban (0.27 [0.18–0.42]), and the Watchman device (0.36 [0.16–0.80]) significantly reduced the risk of any stroke or systemic embolism in nonvalvular AF patients, as well as all‐cause mortality (aspirin: OR, 0.82 [0.68–0.99]; VKA: 0.69 [0.57–0.85]; apixaban: 0.62 [0.50–0.78]; dabigatran: 0.62 [0.50–0.78]; edoxaban: 0.62 [0.50–0.77]; rivaroxaban: 0.58 [0.44–0.77]; and the Watchman device: 0.47 [0.25–0.88]). Apixaban (0.89 [0.80–0.99]), dabigatran (0.90 [0.82–0.99]), and edoxaban (0.89 [0.82–0.96]) reduced risk of all‐cause death as compared to VKA. CONCLUSIONS: The entire spectrum of therapy to prevent thromboembolism in nonvalvular AF significantly reduced stroke/systemic embolism events and mortality.