Comparative Effectiveness and Safety of Apixaban, Rivaroxaban, and Warfarin in Patients With Cirrhosis and Atrial Fibrillation : A Nationwide Cohort Study

Abstract

Background: Apixaban, rivaroxaban, and warfarin have shown benefit for preventing major ischemic events, albeit with increased bleeding risk, among patients in the general population with atrial fibrillation (AF). However, data are scarce in patients with cirrhosis and AF.

Objective: To compare the effectiveness and safety of apixaban versus rivaroxaban and versus warfarin in patients with cirrhosis and AF.

Design: Population-based cohort study.

Setting: Two U.S. claims data sets (Medicare and Optum's de-identified Clinformatics Data Mart Database [2013 to 2022]).

Participants: 1:1 propensity score (PS)-matched patients with cirrhosis and nonvalvular AF initiating use of apixaban, rivaroxaban, or warfarin.

Measurements: Primary outcomes included ischemic stroke or systemic embolism and major hemorrhage (intracranial hemorrhage or major gastrointestinal bleeding). Database-specific and pooled PS-matched rate differences (RDs) per 1000 person-years (PY) and Cox proportional hazard ratios (HRs) with 95% CIs were estimated, controlling for 104 preexposure covariates.

Results: Rivaroxaban initiators had significantly higher rates of major hemorrhagic events than apixaban initiators (RD, 33.1 per 1000 PY [95% CI, 12.9 to 53.2 per 1000 PY]; HR, 1.47 [CI, 1.11 to 1.94]) but no significant differences in rates of ischemic events or death. Consistently higher rates of major hemorrhage were found with rivaroxaban across subgroup and sensitivity analyses. Warfarin initiators also had significantly higher rates of major hemorrhage than apixaban initiators (RD, 26.1 per 1000 PY [CI, 6.8 to 45.3 per 1000 PY]; HR, 1.38 [CI, 1.03 to 1.84]), particularly hemorrhagic stroke (RD, 9.7 per 1000 PY [CI, 2.2 to 17.2 per 1000 PY]; HR, 2.85 [CI, 1.24 to 6.59]).

Limitation: Nonrandomized treatment selection.

Conclusion: Among patients with cirrhosis and nonvalvular AF, initiators of rivaroxaban versus apixaban had significantly higher rates of major hemorrhage and similar rates of ischemic events and death. Initiation of warfarin versus apixaban also contributed to significantly higher rates of major hemorrhagic events, including hemorrhagic stroke.

Primary funding source: National Institutes of Health.

Figure 1.

Cumulative Incidence of the Primary Outcome of Major Hemorrhagic Events (Panel A) or Major Ischemic Events (Panel B) Among Initiators of Rivaroxaban or Apixaban, in the Pooled, PS-Matched Population¹ (N=5,626) Abbreviations: PS, propensity score ¹For details regarding the individual Medicare and Optum databases and method of pooling data, cohort construction and included covariates, propensity score-matching procedures, definitions of all study outcomes, please see the Methods and the Supplementary Appendix.

Figure 2.

Cumulative Incidence of the Primary Outcome of Major Hemorrhagic Events (Panel A) or Major Ischemic Events (Panel B) Among Initiators of Warfarin or Apixaban, in the Pooled, PS-Matched Population¹ (N=5,728) Abbreviations: PS, propensity score ¹For details regarding the individual Medicare and Optum databases, cohort construction and included covariates, propensity score-matching procedures, definitions of all study outcomes, please see the Methods and the Supplementary Appendix.