Higher Rates of Major Hemorrhage with Rivaroxaban and Warfarin
Clinical question: How effective and safe are apixaban versus rivaroxaban versus warfarin in patients with cirrhosis and nonvalvular atrial fibrillation (AF)?
Background: Apixaban, rivaroxaban, and warfarin are commonly used to prevent ischemic events in patients with nonvalvular AF. However, data comparing their safety and effectiveness specifically in patients with cirrhosis and AF remain limited.
Study design: Population-based, retrospective, cohort study
Setting: Two U.S. health-insurance databases—Medicare and Optum (2013 to 2022)
Synopsis: This study examined a propensity-score-matched cohort of 5,570 patients comparing rivaroxaban to apixaban. Rivaroxaban was associated with higher rates of major hemorrhagic events, including major gastrointestinal bleeding and intracranial bleeding (86.9 versus 51.0 per 1,000 person-years), with a hazard ratio (HR) of 1.47 (confidence interval [CI], 1.11 to 1.94). In a separate cohort of 5,704 patients comparing warfarin to apixaban, warfarin was associated with higher rates of major hemorrhagic events (78.9 versus 50.6 per 1,000 person-years), with an HR of 1.38 (CI, 1.03 to 1.84), including significantly higher rates of hemorrhagic stroke (14.6 versus 5.1 per 1,000 person-years), with an HR of 2.85 (CI, 1.24 to 6.59). Rates of ischemic events and all-cause mortality did not differ significantly comparing either rivaroxaban or warfarin versus apixaban. While multiple sensitivity analyses were conducted to adjust for confounding, the observation and nonrandomized nature of the study introduced some limitations.
Bottom line: Rivaroxaban and warfarin were associated with higher rates of major hemorrhage compared to apixaban, with similar rates of ischemic events and mortality in patients with cirrhosis and nonvalvular AF.
Citation: Simon TG, Singer DE, et al. Comparative effectiveness and safety of apixaban, rivaroxaban, and warfarin in patients with cirrhosis and atrial fibrillation: a nationwide cohort study. Ann Intern Med. 2024;177(8):1028-38.
Dr. Siau
Dr. Siau is a clinical assistant professor in the division of hospital medicine at NYU Grossman School of Medicine in New York.