Oral Anticoagulants in Patients With Atrial Fibrillation and Advanced or End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

Background: Patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) face a markedly elevated risk of both thromboembolic and bleeding events. While oral anticoagulation is the cornerstone of stroke prevention in AF, the optimal use of this treatment in patients with stage 4-5 CKD and end-stage renal disease (ESRD) undergoing dialysis remains uncertain, as these populations were largely excluded from the landmark trials that established the efficacy of direct oral anticoagulants (DOACs) in the general AF population. This study aimed to systematically evaluate and compare the efficacy and safety of vitamin K antagonists (VKAs) and DOACs, including factor Xa inhibitors, compared with alternative anticoagulation strategies or no anticoagulation in patients with AF and advanced CKD, including both non-dialysis-dependent stage 4-5 CKD and dialysis-dependent ESRD. Methods: A systematic search of PubMed (MEDLINE), the Cochrane Library, and ClinicalTrials.gov was performed through January 30, 2026. Randomized controlled trials and observational cohort studies evaluating oral anticoagulation in adults with AF and stage 4-5 CKD (estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m Results: A total of 20 studies met the inclusion criteria, comprising four randomized trials, one subgroup analysis of an RCT (ARISTOTLE), and fifteen observational cohorts. Four studies evaluated patients with advanced CKD not receiving dialysis, while sixteen focused on dialysis populations. In non-dialysis stage 4-5 CKD, DOAC therapy, particularly apixaban, was generally associated with comparable or reduced thromboembolic risk and lower rates of major bleeding compared with warfarin. Observational data also suggested a potential mortality benefit with DOACs compared with no anticoagulation. In contrast, findings in dialysis-dependent ESRD were heterogeneous. Warfarin was not consistently associated with reduced stroke risk compared with no anticoagulation and was frequently linked to elevated bleeding risk. Observational studies suggest that apixaban may confer a lower risk of major bleeding compared with VKAs while maintaining similar thromboembolic protection; however, randomized evidence has been limited and underpowered to demonstrate a definitive net clinical benefit. In a meta-analysis of the four dialysis randomized trials (n = 486), factor Xa inhibitors were associated with less ISTH major bleeding than VKAs (pooled risk ratio (RR) 0.64, 95% confidence interval (CI) 0.42-0.99; not retained in Mantel-Haenszel or Hartung-Knapp sensitivity analyses), with no significant difference in stroke, transient ischemic attack or systemic embolism (pooled RR 0.46, 95% CI 0.20-1.02) or all-cause mortality (RR 0.88, 95% CI 0.58-1.35). Conclusion: The risk-benefit profile of oral anticoagulation differs across the CKD spectrum. In stage 4-5 CKD not requiring dialysis, DOACs appear to offer a more favorable safety profile than VKAs while preserving efficacy. In dialysis-dependent ESRD, the net clinical benefit of anticoagulation remains uncertain, particularly for warfarin. Further adequately powered randomized trials are needed to clarify optimal anticoagulation strategies in this high-risk population. Until then, treatment decisions should remain individualized, balancing thromboembolic and bleeding risk. PROSPERO Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261286449.