Abstract
BACKGROUND: Patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) face elevated risks of stroke and bleeding; yet, optimal anticoagulation remains uncertain due to their exclusion from randomized trials. This systematic review and meta-analysis evaluated rivaroxaban vs warfarin in patients with AF and moderate-to-advanced CKD including dialysis. METHODS: We searched PubMed/MEDLINE, Embase, and Cochrane CENTRAL through August 2025 for observational studies comparing rivaroxaban with warfarin in adults with nonvalvular AF and CKD stages 4 to 5 including dialysis. Primary outcomes were stroke/systemic embolism and major bleeding. Pooled hazard ratios (HRs) were calculated using random-effects models. Risk of bias was assessed using ROBINS-I, and certainty of evidence was evaluated using GRADE. RESULTS: Four observational studies encompassing 31,037 patients of whom 12,160 received rivaroxaban and 18,877 received warfarin. Mean age ranged from 66 to 80 years, with CHA(2)DS(2)-VASc scores ranging from 3.5 to 4.5. Reduced-dose rivaroxaban (10-15 mg daily) was commonly prescribed. Compared with warfarin, rivaroxaban demonstrated a 30% reduction in stroke/systemic embolism (pooled HR, 0.70; 95% CI, 0.54-0.92; P = .009; I (2) = 38.1%) and 17% reduction in major bleeding (HR, 0.83; 95% CI, 0.72-0.97; P = .018). Favorable but nonsignificant trends were observed for intracranial hemorrhage (HR, 0.73; 95% CI, 0.49-1.08) and gastrointestinal bleeding (HR, 0.68; 95% CI, 0.46-1.03). Overall evidence quality was moderate according to GRADE assessment. CONCLUSION: In patients with AF and advanced CKD including dialysis, rivaroxaban may be associated with improved efficacy and safety compared with warfarin. However, heterogeneity in CKD stages and off-label dosing practices necessitate prospective randomized trials to establish definitive treatment recommendations.