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. 2025 Jul 14:16:1620394.
doi: 10.3389/fphar.2025.1620394. eCollection 2025.

Effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists in atrial fibrillation patients with liver disease: a systematic review and meta-analysis

Qiang Zhou #  1 , Xiang Liu #  2 , Shuyu Liu  3 , Zhichun Gu  4 , Yanzi Wu  1 , Yuansu Yang  5 , Yingying Tao  1 , Meng Wei  1
Affiliations

Effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists in atrial fibrillation patients with liver disease: a systematic review and meta-analysis

Qiang Zhou et al. Front Pharmacol. .

Abstract

Introduction: Patients with atrial fibrillation (AF) and liver disease, particularly cirrhosis, are frequently excluded from anticoagulation trials, leaving the optimal therapeutic strategy uncertain.

Methods: 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 (risk ratio [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.

Conclusion: 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.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024623387.

Keywords: anticoagulants; atrial fibrillation; direct oral anticoagulants; liver disease; meta-analysis; vitamin K antagonists.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flowchart showing the process of literature screening.
FIGURE 2
FIGURE 2
Meta-analysis of outcomes in patients with liver disease. DOAC, direct oral anticoagulant; VKA, vitamin K antagonist; IS, ischemic stroke; SE, systemic embolism; RR, risk ratio; CI, confidence interval. (A). IS/SE (B). Major bleeding (C). All-cause mortality (D). Gastrointestinal bleeding (E). Intracranial bleeding.
FIGURE 3
FIGURE 3
Meta-analysis of outcomes in patients with liver cirrhosis. DOAC, direct oral anticoagulant; VKA, vitamin K antagonist; IS, ischemic stroke; SE, systemic embolism; RR, risk ratio; CI, confidence interval. (A). IS/SE (B). Major bleeding (C). All-cause mortality (D). Gastrointestinal bleeding (E). Intracranial bleeding.
FIGURE 4
FIGURE 4
Subgroup analysis of data from different regions. DOAC, direct oral anticoagulant; VKA, vitamin K antagonist; IS, ischemic stroke; SE, systemic embolism; RR, risk ratio; CI, confidence interval. (A). Liver disease (B). Liver cirrhosis.
FIGURE 5
FIGURE 5
Subgroup analysis of data from different follow-up durations. DOAC, direct oral anticoagulant; VKA, vitamin K antagonist; IS, ischemic stroke; SE, systemic embolism; RR, risk ratio; CI, confidence interval. (A). Liver disease (B). Liver cirrhosis.
FIGURE 6
FIGURE 6
Subgroup analysis of data for direct oral anticoagulants (DOACs) (A. Rivaroxaban group vs Apixaban group; B. Regular-dose group vs Reduced-dose group). IS, ischemic stroke; SE, systemic embolism; ICH, intracranial hemorrhage; GI, Gastrointestinal; RR, risk ratio; CI, confidence interval. (A). Rivaroxaban vs. Apixaban (B). Regular-dose vs. Reduced-dose.
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