Current Trial-Associated Outcomes With Warfarin in Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation A Meta-analysis

Background: Although several new antithrombotic agents have been developed for stroke prevention in patients with nonvalvular atrial fibrillation (AF), many patients will continue to be treated with warfarin worldwide. Weperformed a meta-analysis of safety and efficacy outcomes in patients with AF treated with warfarin for stroke prevention in large contemporary randomized controlled trials (RCTs). Methods: We searched the MEDLINE, EMBASE, and Cochrane databases for relevant studies; RCTs comparing warfarin with an alternative thromboprophylaxis strategy with at least 400 patients in the warfarin arm and reporting stroke as an efficacy outcome were included. Results: Eight RCTs with 55 789 patient-years of warfarin therapy follow-up were included. Overall time spent in the therapeutic range was 55% to 68%. The annual incidence of stroke or systemic embolism in patients with AF taking warfarin was estimated to be 1.66% (95% CI, 1.41%-1.91%). Major bleeding rates varied from 1.40% to 3.40% per year across the studies. The risk of stroke per year was significantly higher in elderly patients (2.27%), female patients (2.12%), patients with a history of stroke (2.64%), and patients reporting no previous exposure to vitamin K antagonists (1.96%). There was a significant increase in the annual incidence of stroke with progressively increasing CHADS(2) (congestive heart failure, hypertension, age, diabetes, and prior stroke) scores. Conclusions: Current use of warfarin as a stroke prevention agent in patients with AF is associated with a low rate of residual stroke or systemic embolism estimated to be 1.66% per year. Compared with a previous meta-analysis, there has been significant improvement in the proportion of time spent in therapeutic anticoagulation, with a resultant decline in observed stroke rates.