To compare the efficacy and safety of apixaban and rivaroxaban for the prevention of stroke in patients with nonvalvular atrial fibrillation (NVAF) by way of a meta-analysis informed by real-world evidence. Systematic review and meta-analysis of observational studies including patients with NVAF on apixaban and rivaroxaban, which reported stroke/systemic embolism and/or major bleeding. Prospero registration number: CRD42021251719. Estimates of relative treatment effect (based on hazard ratios[HRs]) were pooled using the inverse variance method. Fixed-effects and random effect analyses were conducted. Exploratory meta-regression analyses that included study-level covariates were conducted using the metareg (meta-regression) command of Stata Statistical Software: Release 15.1 (College Station, Texas. StataCorp LLC.). Study level covariates explored in the meta-regression analyses were CHA2DS2-VASc and HAS-BLED scores. A total of 10 unique retrospective real-world evidence studies reported comparative estimates for apixaban versus rivaroxaban in patients with NVAF and were included in the meta-analysis. Adjusted HR was 0.88 (95% [confidence interval] CI 0.81 to 0.95), indicating a significantly lower hazard of stroke/systemic embolism associated with apixaban versus rivaroxaban. Pairwise meta-analysis for a major bleeding episode was significantly lower with apixaban compared with rivaroxaban (HR 0.62; 95% CI 0.56 to 0.69), whereas apixaban was associated with a lower risk of gastrointestinal bleeding compared with rivaroxaban (HR 0.57; 95% CI 0.50 to 0.64). In conclusion, this study suggests that patient CHA2DS2-VASc and HAS-BLED scores might be an important factor when selecting which direct oral anticoagulants to use, given the relation these scores have on treatment outcomes. Apixaban is associated with lower rates of both major and gastrointestinal bleeding than rivaroxaban, with no loss of efficacy.
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