Oral Anticoagulants in Patients With Atrial Fibrillation and Advanced CKD Not Requiring Dialysis

Importance: The net benefit of oral anticoagulants (OACs) in patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) not receiving dialysis remains uncertain. Objective: To compare the estimated effectiveness and safety of apixaban compared with warfarin and no OAC use among patients with AF and advanced CKD not receiving dialysis. Design, Setting, and Participants: This retrospective cohort study used a 3-group target trial emulation framework and included patients from Medicare fee-for-service claims (January 1, 2013, to December 31, 2022) and the Optum deidentified Clinformatics Data Mart database (January 1, 2013, to February 28, 2025). Eligible participants had AF, CKD stage 4 or 5, no prior dialysis, and continuous medical and pharmacy coverage. Data analysis was conducted from February 2025 to June 2026. Exposures: Initiation of apixaban or warfarin vs no oral anticoagulation. Main Outcomes and Measures: Primary outcomes were hospitalization for major bleeding, ischemic stroke, and their composite. Propensity score matching weights were used to balance baseline characteristics, and weighted hazard ratios (HRs) and rate differences (RDs) per 1000 person-years (PYs) were estimated. Results: The study included 14 712 apixaban users (7954 female [54.1%]; mean [SD] age, 78.93 [7.35] years), 6335 warfarin users (3148 female [49.7%]; mean [SD] age, 77.47 [7.03] years), and 21 005 nonusers of OACs (10 797 female [51.4%]; mean [SD] age, 79.59 [7.49] years). Compared with nonusers, apixaban was associated with an increased rate of major bleeding (HR, 1.32 [95% CI, 1.11 to 1.58]; RD, 17.16 [95% CI, 2.45 to 31.87] per 1000 PYs) and a lower rate of ischemic stroke (HR, 0.46 [95% CI, 0.32 to 0.66]; RD, -12.67 [95% CI, -20.65 to -4.69] per 1000 PYs), but there was no association with the composite outcome (HR, 1.05 [95% CI, 0.89 to 1.22]; RD, 6.13 [95% CI, -10.61 to 22.87] per 1000 PYs). Warfarin users had a higher rate of major bleeding (HR, 2.44 [95% CI, 2.06 to 2.88]) and no significant diffrence in the rate of ischemic stroke (HR, 0.87 [95% CI, 0.61 to 1.22]), resulting in a higher rate of the composite outcome compared with nonuse (HR, 1.95 [95% CI, 1.69 to 2.26]). Compared with warfarin, apixaban was associated with lower risk of major bleeding (HR, 0.55 [95% CI, 0.46 to 0.65]) and ischemic stroke (HR, 0.50 [95% CI, 0.33 to 0.78]). Conclusions and Relevance: This study found that among patients with AF and advanced CKD not receiving dialysis, anticoagulation was associated with reduced risk of ischemic stroke, but increased risk of bleeding compared with nonuse, suggesting that the trade-off between ischemic stroke reduction and bleeding risk was more favorable for apixaban than for warfarin.