Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Liver Disease

So Ryoung Lee, Hyun Jung Lee, Eue Keun Choi, Kyung Do Han, Jin Hyung Jung, Myung Jin Cha, Seil Oh, Gregory Y.H. Lip

Research output: Contribution to journalArticle

13 Scopus citations


Background: Advanced liver disease is known to increase the risk for bleeding and affects the hepatic clearance and metabolism of drugs. Subjects with active liver disease were excluded from pivotal clinical trials of direct oral anticoagulants (DOACs), so the evidence regarding the efficacy and safety of DOACs in patients with liver disease is lacking. Objectives: The aim of this study was to compare DOACs with warfarin in patients with nonvalvular atrial fibrillation and liver disease. Methods: Using the Korean National Health Insurance Service database, subjects with atrial fibrillation and active liver disease treated with oral anticoagulation were included (12,778 with warfarin and 24,575 with DOACs), and analyzed ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, all-cause death, and the composite outcome. Propensity score weighting was used to balance covariates between the 2 groups. Results: DOACs were associated with lower risks for ischemic stroke (hazard ratio [HR]: 0.548; 95% confidence interval [CI]: 0.485 to 0.618), intracranial hemorrhage (HR: 0.479; 95% CI 0.394 to 0.581), gastrointestinal bleeding (HR: 0.819; 95% CI: 0.619 to 0.949), major bleeding (HR: 0.650; 95% CI: 0.575 to 0.736), all-cause death (HR: 0.698; 95% CI: 0.636 to 0.765), and the composite outcome (HR: 0.610; 95% CI: 0.567 to 0.656) than warfarin. Among the total study population, 13% of patients (n = 4,942) were identified as having significant active liver disease. A consistent benefit was observed in patients with significant active liver disease (HR for the composite outcome: 0.691; 95% CI: 0.577 to 0.827). Conclusions: In this large Asian population with atrial fibrillation and liver disease, DOACs showed better effectiveness and safety than warfarin, which was consistent in those with significant active liver disease.

Original languageEnglish
Pages (from-to)3295-3308
Number of pages14
JournalJournal of the American College of Cardiology
Issue number25
StatePublished - 2 Jul 2019


  • atrial fibrillation
  • direct oral anticoagulant
  • liver disease
  • warfarin

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