In contrast, dabigatran at a dose of 110 mg bid was not associated with a signi cant difference in the risk of death, nonfatal stroke, nonfa- tal major extracranial bleeding, or systemic embolism (Table 10). ROCKET-AF (Rivaroxaban Once Daily Oral direct Factor Xa inhibition Compared with Vitamin K Antago- nism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) was a double-blind, double- dummy RCT comparing rivaroxaban 20 mg once daily to adjusted-dose warfarin (INR 2.0-3.0) in 14,264 patients with AF at increased risk of stroke (mean CHADS2 score of 3.5).85 In the intention-to- treat analysis, rivaroxaban was noninferior to warfarin for the primary end point of stroke (ischemic or hem- orrhagic) or systemic embolism but was not superior to warfarin (hazard ratio, 0.88; 95% CI, 0.74-1.03). The trial did not nd evidence of a difference in major bleeding between rivaroxaban and warfarin (hazard ratio, 1.04; 95% CI, 0.90-1.20). Major GI bleeding was more common with rivaroxaban than with warfarin (3.2% and 2.2%, respectively, P,.001). Mortality was not signi cantly different between rivaroxaban and warfarin. The Apixaban vs Acetylsalicylic Acid to Prevent Strokes (AVERROES) RCT compared apixaban 5 mg bid to aspirin in 5,599 patients with AF who were demonstrated or expected to be unsuitable candi- dates for adjusted-dose VKA therapy.86 The trial was stopped early for bene t and was consistent with the trials of VKA therapy vs aspirin (section 2.1.3), reporting that apixaban reduces by one-half the occurrence of the primary outcome of stroke and systemic embolism compared with aspirin (hazard ratio, 0.45; 95% CI, 0.32-0.62). 