*2.2.1.6.3. Apixaban*

Compared with warfarin, apixaban is associated with lower risk for intracranial hemorrhage in several real-world studies that included 66.482 patients (HR, 0.45; 95% CI, 0.31–0.63); lower risk for gastrointestinal hemorrhage in 2 studies that included 33.323 patients (HR, 0.63; 95% CI, 0.42–0.95); and lower risk for major hemorrhage in 4 studies that included 89.036 patients (HR, 0.55; 95% CI, 0.48–0.63) [36]. Authors identified only one study of 41.785 patients which assessed death; it reported lower risk with apixaban compared with warfarin (HR, 0.65; 95% CI, 0.56–0.75). Also, they identified only one study of 15.390 patients which assessed the outcome of any stroke or systemic embolism; it reported lower risk of apixaban compared with warfarin (HR, 0.67; 95% CI, 0.46–0.98). There is neither a statistical difference between apixaban and warfarin for the outcomes of ischemic stroke (HR, 0.95; 95% CI, 0.75–1.19) nor for ischemic stroke or systemic embolism (HR, 1.07; 95% CI, 0.87–1.31). Authors reported a significant degree of heterogeneity in the analysis of the outcomes of gastrointestinal hemorrhage but not for the other outcomes.
