For instance, for every 1,000 patients at low risk of stroke with a CHADS2 score of 0, VKA therapy compared with no treatment is anticipated to result in ve fewer nonfatal strokes at the expense of eight more nonfatal major extracranial bleeds and the additional burden of adjusted-dose VKA treatment (Table 3). Although VKA therapy is expected to reduce all-cause mortality in patients with AF in general, it is likely that this mortality bene t does not extend to low-risk patients. The absolute reduction in fatal ischemic stroke with VKA therapy will be far fewer such patients, whereas their absolute increase in fatal intracranial hemor- rhage will be similar to those with higher CHADS2 For patients with a CHADS2 score of 0, treatment with aspirin for 1 year may result in the prevention of two nonfatal strokes per 1,000 patients (moderate- quality evidence due to imprecision) at the expense of three additional nonfatal major extracranial bleeds per 1,000 patients compared with no treatment (Table 4). If stroke rates are truly declining over time, bleeding with oral anticoagulation compared with aspirin. ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) was a double-blind, double-dummy RCT comparing apixaban 5 mg bid to warfarin (INR 2.0-3.0) in 18,201 patients with AF (mean CHADS2 score of 2.1).87 Apixaban reduced by 21% the risk of the primary outcome of stroke (ischemic or hemorrhagic) or systemic embo- lism (hazard ratio, 0.79; 95% CI, 0.66-0.95) and reduced by 31% the risk of major bleeding (hazard ratio, 0.69; 95% CI, 0.60-0.80) compared with warfa- rin. There was no evidence of a difference in major GI bleeding between apixaban and warfarin (hazard was lower with apixaban compared with warfarin (hazard ratio, 0.89; 95% CI, 0.80-0.998). 