Author + information
- Received September 26, 2017
- Revision received December 1, 2017
- Accepted January 1, 2018
- Published online March 5, 2018.
- Antonios Douros, MD, PhDa,b,c,
- Laurent Azoulay, PhDa,b,d,
- Hui Yin, MSca,
- Samy Suissa, PhDa,b and
- Christel Renoux, MD, PhDa,b,e,∗ ()
- aCentre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
- bDepartment of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
- cInstitute of Clinical Pharmacology and Toxicology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- dGerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada
- eDepartment of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
- ↵∗Address for correspondence:
Dr. Christel Renoux, Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine Road, H425.1, Montreal, Quebec H3T 1E2, Canada.
Background Non–vitamin K antagonist oral anticoagulants (NOACs) are relatively new drugs used for stroke prevention in nonvalvular atrial fibrillation (NVAF). However, there are concerns that their use may be associated with hepatotoxic effects.
Objectives The purpose of this study was to determine whether the use of NOACs is associated with an increased risk of serious liver injury compared with the use of vitamin K antagonists (VKAs) in NVAF patients with and without prior liver disease.
Methods Using the administrative databases of the Canadian province of Quebec’s health insurances, the authors conducted a cohort study among patients newly diagnosed with NVAF between January 2011 and December 2014. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of serious liver injury (defined as either a hospitalization or related death) were estimated using time-dependent Cox proportional hazards models, comparing current use of NOACs to current use of VKAs separately among patients with or without prior liver disease.
Results The cohort comprised 51,887 patients, including 3,778 with prior liver disease. During 68,739 person-years of follow-up, 585 patients experienced a serious liver injury. Compared with current use of VKAs, current use of NOACs was not associated with an increased risk of serious liver injury in patients without or with prior liver disease (adjusted HR: 0.99; 95% CI: 0.68 to 1.45; and adjusted HR: 0.68; 95% CI: 0.33 to 1.37, respectively).
Conclusions Compared with VKAs, NOACs were not associated with an increased risk of serious liver injury irrespective of baseline liver status. Overall, these results provide reassurance regarding the hepatic safety of NOACs.
This work was supported by an infrastructure grant from the Canadian Foundation for Innovation, and the database was acquired thanks to unrestricted funding from Bayer Pharma AG. The sponsors had no other role in the study. Dr. Douros has received a research fellowship from the German Research Foundation (Deutsche Forschungsgemeinschaft). Dr. Azoulay has received a Chercheur-Boursier Award from the Fonds de recherche du Québec–Santé and a William Dawson Scholar award from McGill University. Dr. Suissa has received the James McGill Professorship award; has received research grants from Bayer Pharma, Boehringer Ingelheim, and Bristol-Myers Squibb; and has participated in advisory board meetings or as a speaker for AstraZeneca, Boehringer Ingelheim, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received September 26, 2017.
- Revision received December 1, 2017.
- Accepted January 1, 2018.
- 2018 American College of Cardiology Foundation
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