Author + information
- Received January 22, 2019
- Revision received April 2, 2019
- Accepted April 8, 2019
- Published online June 24, 2019.
- So-Ryoung Lee, MDa,∗,
- Hyun-Jung Lee, MDa,∗,
- Eue-Keun Choi, MD, PhDa,∗ (, )@SNUnow,
- Kyung-Do Han, PhDb,
- Jin-Hyung Jung, BScb,
- Myung-Jin Cha, MDa,
- Seil Oh, MD, PhDa and
- Gregory Y.H. Lip, MDa,c,d
- aDivision of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, KoreaDivision of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- bDepartment of Medical Statistics, College of Medicine, Catholic University of Korea, Seoul, KoreaDepartment of Medical Statistics, College of Medicine, Catholic University of Korea, Seoul, Korea
- cLiverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Chest & Heart Hospital, Liverpool, United KingdomLiverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Chest & Heart Hospital, Liverpool, United Kingdom
- dAalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkAalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
- ↵∗Address for correspondence:
Dr. Eue-Keun Choi, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea.
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.
↵∗ Drs. S.-R. Lee and H.-J. Lee contributed equally to this work.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
This study was supported by the Korea National Research Foundation funded by the Ministry of Education, Science and Technology (grant 2014R1A1A2A16055218). Dr. Choi has received research grants from Daiichi-Sankyo, Bristol-Myers Squibb/Pfizer, and Biosense Webster. Dr. Lip has served as a consultant for Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi-Sankyo; and has served as a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received January 22, 2019.
- Revision received April 2, 2019.
- Accepted April 8, 2019.
- 2019 American College of Cardiology Foundation
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