Over a median follow-up of 707 days, the primary end point of ischemic and hemor- rhagic stroke and systemic embolism in patients as actually treated (the prespecified analysis plan for efficacy in this study) occurred in 1.7%/y in those receiving rivaroxaban and 2.2%/y in those on warfarin (HR, 0.79; 95% CI, 0.66 0.96; P<0.001 for noninferiority; analyzed by intention to treat, HR, for superiority). The primary safety end point of major or nonmajor bleeding occurred in 14.9% of patients per year in those receiving rivaroxaban and 14.5% in those on warfarin reduced on rivaroxaban relative to warfarin. Subsequent sub- group analysis of the 6796 subjects without previous stroke found rivaroxaban to have borderline superiority to warfarin in intention-to-treat analysis of efficacy (HR, 0.77; 95% CI, 0.58 1.01), supporting its use in primary prevention. Other subgroup analyses397 found no differences in the effec- tiveness of rivaroxaban according to age, sex, CHADS2 score, or the presence of moderate renal insufficiency399 (creatinine clearance, 30 to 49 mL/min; these subjects were randomized to rivaroxaban 15 rather than 20 mg/d). Important concerns have been raised about the interpretation of ROCKET AF, most notably the relatively poor management of warfarin (mean time in therapeutic range, 55%) and the relatively high number of outcomes (stroke or systemic embolism) beyond the 2-day monitoring period after drug cessation.400 Apixaban has been studied in 2 phase III trials. The Apixaban Versus Acetylsalicylic Acid to Prevent Strokes in Atrial Fibrillation Patients Who Have Failed orAre Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial401 compared apixaban 5 mg twice daily with aspirin 81 to 324 mg daily in 5599 subjects with nonvalvular AF unsuitable for warfarin therapy. 