Stroke prevention in atrial fibrillation: The multicenter, double-blind, randomized phase 3 Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial compared apixaban (5 mg bid) with warfarin (dose-adjusted to achieve an INR of 2-3) in 18,201 patients with atrial fibrillation with at least one additional risk factor for stroke.130 The rate of primary efficacy outcome, a composite of stroke (ischemic or hemorrhagic) and systemic embolism, was 1.27% per year in the apixaban group and 1.60% per year in the warfarin group (HR, 0.79; 95% CI, 0.66-0.95; P < .001 for noninferiority and P < .01 for superiority). Annual rates of major bleeding with apixaban and warfarin were 2.13% and 3.09%, respectively (HR, 0.69; 95% CI, 0.60-0.80; P < .001) and rates of hemorrhagic stroke were 0.24% and 0.47%, respectively (HR, 0.51; 95% CI, 0.35-0.75; P < .001). The rates of ischemic stroke were similar with apixaban and warfarin (0.97% and 1.05%, respectively). All-cause mortality was lower with apixaban than with warfarin (3.52% and 3.94%, respectively; P = .047). Therefore, apixaban was superior to warfarin in preventing stroke and systemic embolism and produced less bleeding. Enrollment has been completed and patients are now undergoing follow-up. In the multicenter, double-blind, phase 3 AVERROES trial, the same apixaban regimen was compared with aspirin in 5,600 patients with atrial fibrillation who were ineligible for vitamin K antagonist treatment or could not tolerate such therapy.131 Compared with aspirin, treatment with apixaban reduced the rate of stroke or systemic embolism from 3.6% to 1.6% (RR, 0.46; 95% CI, 0.33-0.64). Rates of major bleeding were similar with apixaban and aspirin (1.4% and 1.2%, respectively).