The majority of the patients in ATRIA had a CHADS score of 1. c VKA therapy likely does not lead to any reductions in all-cause mortality compared with no therapy in low-risk patients with a CHADS score of because there is evidence suggesting that absolute reductions in ischemic stroke heavily depend on stroke risk (eg, small reductions at low CHADS score), whereas the absolute increase in intracranial hemorrhage is relatively consistent across CHADS categories (Singer et al ). d Intracranial hemorrhage includes intracerebral, subdural, and subarachnoid bleeds. For studies that did not report the number of strokes that were fatal and nonfatal (CAFA, EAFT), we imputed values for the number of fatal and nonfatal strokes to estimate the pooled relative risk for nonfatal stroke across all eligible studies. Assumptions underlying these estimates are detailed in the section of this article. e Of the nonfatal strokes on no therapy, an estimated were ischemic, and two were hemorrhagic. f Of the nonfatal strokes on VKA therapy, an estimated were ischemic, and two were hemorrhagic. g We estimated the annual rates of nonfatal stroke (ischemic and hemorrhagic) on no therapy by extrapolating from observed annual rates of ischemic stroke (fatal nonfatal), strati ed by CHADS score, in the aspirin arms of six historical RCTs in patients with AF (Gage et al ). Assumptions underlying these estimates are detailed in the section of this article. h Estimate of the rate of nonfatal major extracranial bleeding on no therapy is derived from rates in observational cohorts of predominantly patients with AF receiving adjusted-dose VKA therapy (median, and dividing by the relative risk of major bleeding on adjusted-dose VKA therapy observed in the RCTs (see section of this article). 