Assumptions underlying these estimates are detailed in section of this article. g The published report did not provide the number of major extracranial bleeds that were fatal and nonfatal; therefore, we imputed values for the number of fatal and nonfatal major extracranial bleeds to estimate the relative risk for nonfatal major extracranial bleeds. Assumptions underlying these estimates are detailed in section of this article. h Rate of nonfatal major extracranial bleeding on warfarin is from observational cohorts of patients receiving adjusted-dose VKA therapy (median, 1.3%/y). i Based on rate of systemic embolism on aspirin of per patient-y reported in the IPD meta-analysis of warfarin vs aspirin by van Walraven et al and a relative risk for systemic embolism of with VKA vs aspirin ( Table ). e556S Antithrombotic Therapy for Atrial Fibrillation no reduction in all-cause mortality. However, because absolute rates of stroke may have fallen over the past 2 decades, we may be overestimating the abso- lute reduction in nonfatal stroke achieved with VKA therapy. Moreover, the true extent of bleeding risk with VKA therapy compared with aspirin therapy is unclear because the pooled estimate of the relative risk of bleeding from the relevant RCTs is imprecise (Table 5). The limited ability of CHADS2 to accu- rately predict stroke risk (C statistic, 0.6-0.7), the considerable variability in patient values and pref- erences, and the burden and lifestyle limitations associated with adjusted-dose VKA therapy, intro- duce further uncertainty. Compared with combination therapy with aspirin and clopidogrel, VKA therapy is expected to result in six fewer nonfatal strokes per 1,000 patients over a 1-year period, anywhere from four fewer to three more nonfatal major extracranial bleeds, and no reduction in all-cause mortality (Table 6). 