SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Drugs Outcomes Research and Policies
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1620394
Effectiveness and Safety of Direct Oral Anticoagulants Versus Vitamin K Antagonists in Atrial Fibrillation Patients with Liver Disease: A Systematic Review and Meta-analysis
Provisionally accepted
- 1Affiliated Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
- 2Jiangsu College of Nursing, Huai'an, China
- 3Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Patients with atrial fibrillation (AF) and liver disease, particularly cirrhosis, are frequently excluded from anticoagulation trials, leaving the optimal therapeutic strategy uncertain.This study aimed to compare the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with AF and liver disease. We systematically searched the PubMed, Cochrane Library, Medline, and Embase databases for relevant studies published up to November 2024.Results: Fourteen studies, involving 44,848 participants, were included. Compared to VKAs, DOACs were associated with significantly lower risks of major bleeding (relative risk [RR]: 0.64, 95% confidence interval [CI]: 0.55-0.75; P < 0.0001), intracranial bleeding (RR: 0.43, 95% CI: 0.33-0.56; P < 0.0001), gastrointestinal (GI) bleeding (RR: 0.72, 95% CI: 0.59-0.89; P = 0.002), and all-cause mortality (RR: 0.83, 95% CI: 0.70-0.98; P =0.03). No significant difference was observed in ischemic stroke/systemic embolism (RR: 0.77, 95% CI: 0.52-1.13; P = 0.19). In patients with cirrhosis, DOACs were similarly superior for major bleeding, GI bleeding, and intracranial bleeding. Subgroup analyses revealed that apixaban demonstrated a more favorable safety profile than rivaroxaban in patients with liver disease, whereas both agents showed comparable effectiveness and safety in cirrhotic patients.DOACs are safer and equally effective alternatives to VKAs in patients with AF and liver disease, including those with cirrhosis. In patients with liver disease, apixaban may offer additional safety benefits compared with rivaroxaban. However, in patients with cirrhosis, the effectiveness and safety profiles of the two drugs are similar.
Keywords: Atrial Fibrillation, Liver disease, direct oral anticoagulants, Vitamin K antagonists, Anticoagulants, Meta-analysis
Received: 29 Apr 2025; Accepted: 27 Jun 2025.
Copyright: © 2025 Zhou, Liu, Liu, Gu, Wu, Yang, Tao and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Meng Wei, Affiliated Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
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