Abstract P431: Comparative Safety and Effectiveness of Direct Oral Anticoagulants versus Warfarin in Patients With Non-Valvular Atrial Fibrillation and Severe Chronic Kidney Disease

Background: Landmark trials of direct oral anticoagulants (DOACs) versus warfarin for non-valvular atrial fibrillation (NVAF) excluded patients with severe chronic kidney disease (CKD). Real-world data on safety and effectiveness of DOACs in severe CKD is limited. Methods: New users of DOACs (apixaban, rivaroxaban, and dabigatran) or warfarin with NVAF and severe CKD between 2010 and 2020 were identified using the de-identified electronic health records form the Optum Labs Data Warehouse. We estimated the risks of bleeding, ischemic stroke, and death for apixaban and rivaroxaban separately (vs. warfarin) using Cox regression models. Incidence rate (IR) and hazard ratio (HR) were adjusted for baseline characteristics by inverse probability of treatment weighting (IPTW). Dabigatran users were not included for the analysis due to small sample size (n=318). Results: Compared with warfarin users (n=7548), apixaban users (n=3719) were older (mean age 77 vs. 76 years) and had more hypertension (94% vs. 90%). In IPTW analysis, apixaban was associated with a lower risk of any bleeding (HR [95% CI], 0.71 [0.56, 0.89]), as well as major bleeding (HR [95% CI], 0.61 [0.46, 0.81]). There were no significant differences in ischemic stroke and death between apixaban and warfarin users ( Figure A ). Rivaroxaban users (n=920) were older (mean age 76 vs. 75 years) and had higher estimated glomerular filtration rate than warfarin users (mean: 25 vs. 23 ml/min/1.73 m 2 ). In IPTW analysis, risks of bleeding were higher among rivaroxaban users than warfarin users (any bleeding: HR [95% CI], 1.43 [1.05, 1.95]; major bleeding: HR [95% CI], 1.54 [1.09, 2.17]), with no significant differences in ischemic stroke and death ( Figure B ). Conclusion: Apixaban was associated with a lower risk of bleeding, but rivaroxaban was associated with a higher risk of bleeding, compared with warfarin in patients with NVAF and severe CKD. Risks of ischemic stroke and death were similar between agents. Apixaban may be a preferable oral anticoagulant in this population.