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.

The authors have declared no competing interest.

This work was supported by grants from the Chang Gung Memorial Hospital, Taiwan (CMRPG2N0041).

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The data were retrieved from the Chang Gung Research Database. Due to retrospective nature of the database study, the hospital identification number of each patient was encrypted and de-identified to protect their privacy. Therefore, informed consent was waived for this study. The institutional review board of Chang Gung Memorial Hospital approved the study protocol (IRB No. :202200625B0).

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