Comparative safety and effectiveness of warfarin or rivaroxaban versus apixaban in patients with advanced CKD and atrial fibrillation: nationwide US cohort study

Abstract

Rationale & Objective: Head-to-head data comparing the effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) are lacking. We compared the safety and effec tiveness of warfarin or rivaroxaban versus apix aban in patients with AF and non–dialysis dependent CKD stage 4/5. Study Design: Propensity score–matched cohort study. Setting & Participants: 2 nationwide US claims databases, Medicare and Optum’s deidentified Clinformatics Data Mart Database, were searched for the interval from January 1, 2013, through March 31, 2022, for patients with nonvalvular AF and CKD stage 4/5 who initiated warfarin versus apixaban (matched cohort, n = 12,488) and rivaroxaban versus apixaban (matched cohort, n = 5,720). matching was used to adjust for 80 potential confounders. Results: Compared with apixaban, warfarin initia tion 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). Compared with apixaban, rivaroxaban 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) and rivaroxaban (0.94; 0.81-1.10) versus 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) versus apixaban, but the CIs were wide. Similar results were observed for warfarin versus apixaban in the positive control cohort of patients with CKD stage 3, consistent with randomized trial findings. Exposures: Warfarin, rivaroxaban, or apixaban. Outcomes: Primary outcomes included major bleeding and ischemic stroke. Secondary out comes included all-cause mortality, major gastrointestinal bleeding, and intracranial bleeding. Analytical Approach: Cox regression was used to estimate HRs, and 1:1 propensity-score Limitations: Few ischemic stroke events, poten tial residual confounding. Conclusions: In patients with AF and advanced CKD, rivaroxaban and warfarin were associated with higher rates of major bleeding compared with apixaban, suggesting a superior safety pro f ile for apixaban in this high-risk population.