Abstract
BACKGROUND: Direct oral anticoagulants (DOACs) are the standard of care for treatment of venous thromboembolism and stroke prophylaxis in atrial fibrillation. Since patients with Child-Pugh (CP) B or C liver cirrhosis are underrepresented in trials, the safety of DOACs in this population is unclear. OBJECTIVES: This study synthesized primary evidence on the safety profile of DOACs in patients with advanced liver cirrhosis. METHODS: A literature search of MEDLINE and Embase from inception to October 2025 identified randomized and nonrandomized cohort studies comparing DOAC with vitamin K antagonists or low-molecular-weight heparin in patients with liver cirrhosis. Screening and data collection were conducted in duplicate. The primary outcome was major bleeding defined by International Society on Thrombosis and Haemostasis criteria, stratified by CP class. Data were meta-analyzed using a random-effects model, presented as odds ratios (OR) with corresponding 95% CIs. RESULTS: Of 797 articles captured in the literature search, 15 nonrandomized (n = 17,387) and 1 randomized (n = 70) study were included. DOACs reduced major bleeding in both CP class B and C exclusive subgroup and a subgroup with unspecified CP stages of liver cirrhosis (CP B and C: OR, 0.53; 95% CI, 0.36-0.80; CP unspecified: OR, 0.66; 95% CI, 0.46-0.98). CONCLUSION: Based on the findings of this meta-analysis, DOACs may be associated with a reduced risk of major bleeding compared with vitamin K antagonists or low-molecular-weight heparin in patients with liver cirrhosis, including those with CP class B and C cirrhosis. The results of this meta-analysis should be interpreted in the context of methodological limitations. Future analysis should evaluate the impact of specific DOACs and dosage on safety outcomes in this patient population.