Carlos Nuñez Aguillon, PharmD; Minnesota Community Care | La Clinica
Background: Use of warfarin and DOACs such as apixaban and rivaroxaban are first-line therapies for anticoagulation in atrial fibrillation (AF), the most common arrhythmia. Although AF is more common in patients with cirrhosis than in the general population, trials and guidelines comparing these oral anticoagulants (OAC) in AF have excluded this population. Clinicians making clinical decisions on which OACs to use in patients with cirrhosis and non-valvular AF is limited and may lead to serious efficacy and safety concerns.
Purpose: The purpose of this study was to compare apixaban vs rivaroxaban and warfarin in their safety and effectiveness in patients with cirrhosis and AF. Safety and efficacy were determined by rates of hemorrhagic events (hemorrhagic stroke, other intracranial bleeding, major gastrointestinal (GI) bleeding, or non-GI bleeding) and major ischemic events (hospitalization for ischemic stroke or systemic embolism).
Study Design: In this retrospective cohort study, investigators analyzed two U.S. claims databases, Medicare and Optum, identifying adults with non-valvular AF and cirrhosis through International Classification of Disease (ICD) codes. The claims data included Medicare, Medicare Advantage, and employer-sponsored health insurance. This study included patients diagnosed with AF and cirrhosis who filled an initial prescription for standard dosing of apixaban 5 mg twice daily and rivaroxaban 20 mg once daily, reduced dose of apixaban 2.5 mg twice daily and rivaroxaban 15 mg once daily, and warfarin. Additionally, the groups were 1:1 propensity score (PS)-matched to account for cirrhosis severity and CHADS2-VASC scores with an opposing exposure.
Results: This study involved 5,570 patients starting rivaroxaban or apixaban, and 5,704 patients starting warfarin or apixaban, all matched 1:1 by propensity score. The mean ages were 72.8 and 73.0 for apixaban and rivaroxaban respectively, and 73.7 and 73.8 for apixaban and warfarin respectively. Rivaroxaban had significantly higher major bleeding rates compared to apixaban (HR 1.47; 95% CI, 1.11 to 1.94), but similar ischemic stroke rates (HR 0.88; 95% CI, 0.37 to 2.06). At a reduced dose, rivaroxaban showed no significant difference in major bleeding (HR 1.65; 95% CI, 0.94 to 2.9) or ischemic stroke (HR 0.52; 95% CI, 0.05 to 5.71). Patients with decompensated cirrhosis initiating rivaroxaban experienced significantly higher absolute rates of hemorrhagic events when compared to apixaban (RD 45.2 per 1000 PY; 95% CI, 1.6 to 88.8 per 1000 PT) but did not result in statistically significant higher risk (HR 1.65; 95% CI, 0.99 to 2.77). Warfarin had significantly higher major bleeding rates compared to apixaban (HR 1.38; 95% CI, 1.03 to 1.84), but similar ischemic stroke rates (HR 1.09; 95% CI, 0.51 to 2.35). When assessing compensated cirrhosis patients, initiating warfarin resulted in significantly higher absolute rates of major hemorrhagic events when compared to apixaban (RD 22.5 per 1000 PY; 95% CI, 11.1 to 33.9 per 1000 PY), although it did not result in significantly higher risk (HR 1.29; 95% CI, 0.89 to 1.87). In decompensated patients, warfarin initiator also saw significantly higher rates of major hemorrhagic events than apixaban (RD 42.2 per 1000 PY; 95% CI, 22.1 to 62.2 per 1000 PY), but did not result in significantly higher risk (HR 1.54; 95% CI, 0.97 to 2.43). Overall, all-cause mortality was not significantly different between rivaroxaban (HR 1.1; 95% CI, 0.9 to 1.35) or warfarin (HR 1.09; 95% CI, 0.91 to 1.31) and apixaban.
Conclusion: Overall, the study concluded that the choice and dosing of OAC in patients with cirrhosis and AF can affect clinical outcomes and the safety of the patient. Similar to other studies that excluded cirrhosis patients, overall rates of major bleeding in this study were lower when apixaban was used. In decompensated cirrhosis patients, higher rates of major bleeding were observed in rivaroxaban and warfarin but significantly higher risk was not observed. This can also be noted for compensated cirrhosis patients initiating warfarin when compared to apixaban initiators. In the clinical setting, apixaban may be the preferred choice of OAC in this population due to the reduced risk of major bleeding events.
Key Point: Patients with cirrhosis and AF starting standard dosing of rivaroxaban and warfarin had higher rates of hemorrhagic events when compared to the standard dose of apixaban. No statistical difference in risk of hemorrhagic events was observed when comparing reduced doses of apixaban and rivaroxaban. Rates of ischemic stroke and all-cause mortality were similar in the apixaban vs rivaroxaban and apixaban vs warfarin groups.
References:
- Simon TG, Singer DE, Zhang Y, 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. Published online July 9, 2024. doi:10.7326/M23-3067
- Lip GYH, Banerjee A, Boriani G, et al. Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report. Chest. 2018;154(5):1121-1201. doi:10.1016/j.chest.2018.07.040