Effectiveness and Safety of Apixaban, Rivaroxaban and Warfarin in Patients with Advanced Kidney Disease and Atrial Fibrillation: a Nationwide US Cohort Study
Postdoctoral fellow Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, United States
Background: Head-to-head data comparing the effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and advanced CKD are lacking, since they have been underrepresented in randomized controlled trials.
Objectives: To compare the safety and effectiveness of warfarin or rivaroxaban vs. apixaban in patients with AF and non-dialysis CKD stages 4-5.
Methods: We constructed two new-user, active-comparator cohorts using data from two nationwide U.S. claims databases, Medicare and Optum Clinformatics® Data Mart Database (01/01/2013-03/31/2022). We included patients with nonvalvular AF and CKD who newly initiated warfarin vs. apixaban or rivaroxaban vs. apixaban. CKD stages were determined based on a validated claims-based algorithm. The primary safety outcome was major bleeding and the primary effectiveness outcome was ischemic stroke. Secondary outcomes included all-cause mortality, major gastrointestinal bleeding and intracranial bleeding. We used 1:1 propensity score matching to adjust for 80 confounders. Adjusted hazard ratios (HRs) were estimated with Cox regression analyses in the propensity score matched sample.
Results: Compared with apixaban, warfarin initiation was associated with a higher rate of major bleeding (HR 1.85; 95% CI 1.59-2.15), including major gastrointestinal bleeding (1.86; 1.53-2.25) and intracranial bleeding (2.15; 1.42-3.25). Rivaroxaban vs. apixaban was also associated with a higher rate of major bleeding (1.69; 1.33-2.15). All-cause mortality was similar for warfarin (1.08; 0.98-1.18) or rivaroxaban (0.94; 0.81-1.10) vs. apixaban. Furthermore, no statistically significant differences for ischemic stroke were observed for warfarin (1.14; 0.83-1.57) or rivaroxaban (0.71; 0.40-1.24) vs. apixaban, although confidence intervals were wide. Similar results were observed for warfarin vs. apixaban in the positive control cohort of patients with CKD stage 3, consistent with randomized trial findings.
Conclusions: In patients with AF and advanced CKD, rivaroxaban and warfarin were associated with a higher rate of major bleeding compared with apixaban, suggesting a superior safety profile for apixaban in this high-risk population.
