Efficacy and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients with Non-valvular Atrial Fibrillation and Liver Cirrhosis

Background Evidence of the pharmacodynamics of direct oral anticoagulants (DOACs) is limited in patients with atrial fibrillation (AF) and liver cirrhosis (LC). This study aimed to compare the efficacy and safety of DOACs versus warfarin in patients with non-valvular AF and LC. Methods We conducted a new-user, retrospective cohort study involving patients with AF and LC from the Chang Gung Hospital System for the years 2012–2021. LC was categorized per the Child–Pugh classification system. We divided the included patients into two cohorts, namely a DOAC cohort and a warfarin cohort. The measured outcomes were thromboembolic events (ischemic stroke [IS], transient ischemic attack [TIA], and systemic embolism [SE]), intracranial hemorrhage [ICH], gastrointestinal (GI) and major bleeding, and all-cause mortality. Results In total, 478 DOAC users and 247 warfarin users were included in the analysis. DOACs and warfarin exhibited comparable efficacy in preventing thromboembolic events, namely IS (adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 0.42–2.61), TIA (aHR, 1.36; 95% CI, 0.18–10.31]), and SE (aHR, 0.49; 95% CI, 0.14–1.70). DOAC use was associated with a similar risk of ICH (aHR, 0.65; 95% CI, 0.26–1.59) and GI bleeding (aHR, 0.64; 95% CI, 0.39–1.03), a decreased risk of major bleeding (aHR, 0.64; 95% CI, 0.42–0.99), and a reduction in all-cause mortality (aHR, 0.73; 95% CI, 0.54–0.99). Patients with Child– Pugh class A classification exhibited a significant reduction in major bleeding risk in DOAC users (aHR, 0.48; 95% CI, 0.33–0.70); however, this reduction was nonsignificant for patients with class B or C classification (aHR, 0.77; 95% CI, 0.54−1.08) Conclusion Relative to warfarin, DOACs provide comparable efficacy but greater safety for patients with non-valvular AF and LC. Specifically, DOAC use leads to a lower risk of major bleeding and a lower all-cause mortality. Clinical Perspective What is New? This study reveals that direct oral anticoagulants (DOACs) and warfarin have similar effectiveness in preventing thromboembolic events in patients with non-valvular atrial fibrillation (AF) and liver cirrhosis (LC). DOACs demonstrate a lower risk of major bleeding and reduced all-cause mortality compared to warfarin, especially in patients with Child–Pugh class A LC. The safety profile of DOACs in reducing gastrointestinal bleeding is comparable to that of warfarin, with a trend towards lower risk. What are the Clinical Implications? For patients with non-valvular AF and LC, particularly those with Child–Pugh class A classification, DOACs may be a safer alternative to warfarin due to their lower risk of major bleeding. Clinicians can consider DOACs as a comparable alternative to warfarin for stroke prevention in this patient group, given their similar efficacy in preventing thromboembolic events. The reduced all-cause mortality associated with DOACs highlights their potential benefit in improving overall patient outcomes in the context of AF and LC.