Effectiveness and safety of apixaban and warfarin in patients with new-onset atrial fibrillation after advanced chronic kidney disease or end-stage kidney disease

BACKGROUND Limited evidence supports the use of apixaban for atrial fibrillation (AF) in patients with severe chronic kidney disease (CKD) or end-stage kidney disease (ESKD) when warfarin is often contraindicated. OBJECTIVE Through an extensive cohort study, we attempted to compare the outcomes of apixaban and warfarin in patients within this population. METHODS Using TriNetX data (2017-2023), we compared apixaban and warfarin in patients with chronic AF after stage 5 CKD or ESKD. Propensity score matching (PSM) and Cox multivariate analysis were applied to reduce bias. Only exclusive users were included to prevent switching influence. Subdistribution hazard ratios (SHRs) and 95% confidence intervals (CIs) for outcomes (cerebrovascular events, bleeding, and mortality) were adjusted for competing risks. Subgroup analyses considered sex, age, and dialysis status. We also compared apixaban doses to evaluate dose-related effects. RESULTS After 1:1 PSM, our analysis included 1364 cases per group. The apixaban group showed significant advantages over the warfarin group in effectiveness (cerebral infarction: SHR 0.72; 95% CI 0.60-0.85; hemorrhagic stroke: SHR 0.42, 95% CI 0.28-0.63; cerebrovascular events: SHR 0.69, 95% CI 0.59-0.81), bleeding safety (gastrointestinal bleeding: SHR 0.77, 95% CI 0.61-0.97; blood transfusion: SHR 0.73, 95% CI 0.61-0.87; bleeding-related outcomes: SHR 0.75, 95% CI 0.64-0.87), and all composite outcomes (SHR 0.69, 95% CI 0.61-0.78). Subgroup analyses showed consistent improvements across gender, age, and dialysis status. Warfarin's time in therapeutic range was 44.4%. Sensitivity analysis still lacks sufficient evidence to determine whether the 5-mg or 2.5-mg dose of apixaban is superior. CONCLUSION This large cohort study highlights the lower risks of cerebrovascular events and bleeding associated with apixaban in patients with stage 5 CKD or those undergoing hemodialysis. However, the optimal dosage of apixaban requires further investigation in future studies.