Antonios Douros1, Laurent Azoulay2, Hui Yin3, Samy Suissa4, Christel Renoux5. 1. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada; Institute 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. 2. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada; Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada. 3. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. 4. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada. 5. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. Electronic address: christel.renoux@mcgill.ca.
Abstract
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.
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 NVAFpatients 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.