Anticoagulation in Older Adults With Advanced Chronic Kidney Disease and Atrial Fibrillation: Comparative Safety of Apixaban, Rivaroxaban, and Warfarin

Background: Older adults with atrial fibrillation (AF) and chronic kidney disease (CKD) stage 4–5 have simultaneously high risks of ischemic stroke and anticoagulant-related bleeding. Evidence guiding drug selection is limited because pivotal direct oral anticoagulant (DOAC) trials largely excluded patients with severe renal impairment. Objective: To review contemporary comparative evidence for apixaban, rivaroxaban, and warfarin in older adults with advanced CKD, with emphasis on major bleeding, thromboembolism, renal function, dose selection, and the distinction between non-dialysis CKD and kidney failure requiring dialysis. Summary: Observational data consistently suggest that apixaban is associated with less major bleeding than warfarin or rivaroxaban in non-dialysis CKD stage 4–5, while stroke rates appear broadly similar but are less precisely estimated. A 2024 nationwide US cohort found major bleeding to be higher with warfarin and rivaroxaban than with apixaban. A separate cohort of patients with severe CKD, mean age 78.5 years, similarly found lower major bleeding with apixaban than with warfarin or rivaroxaban. Recent 2026 analyses continue to support a favorable apixaban safety signal, but certainty remains limited by confounding and sparse randomized evidence. In dialysis, small randomized trials have not established clear superiority of apixaban or vitamin K antagonists. Conclusion: In older adults with AF and non-dialysis advanced CKD who require anticoagulation, apixaban currently has the most consistent observational safety signal. Warfarin remains appropriate in selected patients, particularly when DOACs are unsuitable. Anticoagulation in kidney failure requiring dialysis should remain individualized because the net clinical benefit is uncertain.