Prospective study of oral anticoagulants and risk of liver injury in patients with atrial fibrillation

• Type of Material: Article
• Authors: Alvaro Alonso, Emory University; Richard F. MacLehose, University of Minnesota; Lin Y. Chen, University of Minnesota; Lindsay G.S. Bengtson, Optum; Alanna M. Chamberlain, Mayo Clinic; Faye L. Norby, University of Minnesota; Pamela L. Lutsey, University of Minnesota
• Language: English
• Date: 2017-06-01
• Publisher: BMJ Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017, BMJ Publishing Group. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1136/heartjnl-2016-310586
• Title of Journal or Parent Work: Heart
• ISSN: 1355-6037
• Volume: 103
• Issue: 11
• Start Page: 834
• End Page: 839
• Grant/Funding Information: This work was supported by grant R01-HL122200 from the National, Heart, Lung and Blood Institute and American Heart Association grant 16EIA26410001 (Alonso).
• Keywords: WARFARIN; Cardiovascular System & Cardiology; Science & Technology; METAANALYSIS; APIXABAN; ACUTE HEPATITIS; SAFETY; HEPATOTOXICITY; Life Sciences & Biomedicine; DABIGATRAN; CODES; RIVAROXABAN; Cardiac & Cardiovascular Systems
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Public Health

Abstract

Objective: To assess the risk of liver injury hospitalisation in patients with atrial fibrillation (AF) after initiation of direct oral anticoagulants (DOACs) or warfarin and to determine predictors of liver injury hospitalisation in this population. Methods: We studied 113 717 patients (mean age 70, 39% women) with AF included in the MarketScan Commercial and Medicare Supplemental databases with a first prescription for oral anticoagulation after 4 November 2011, followed through 31 December 2014. Of these, 56 879 initiated warfarin, 17 286 initiated dabigatran, 30 347 initiated rivaroxaban and 9205 initiated apixaban. Liver injury hospitalisation and comorbidities were identified from healthcare claims. Results: During a median follow-up of 12 months, 960 hospitalisations with liver injury were identified. Rates of liver injury hospitalisation ( per 1000 person-years) by oral anticoagulant were 9.0 (warfarin), 4.0 (dabigatran), 6.6 (rivaroxaban) and 5.6 (apixaban). After multivariable adjustment, liver injury hospitalisation rates were lower in initiators of DOACs compared with warfarin: HR (95% CI) of 0.57 (0.46 to 0.71), 0.88 (0.75 to 1.03) and 0.70 (0.50 to 0.97) for initiators of dabigatran, rivaroxaban, and apixaban, respectively (vs. warfarin). Compared with dabigatran initiators, rivaroxaban initiators had a 56% increased risk of liver injury hospitalisation (HR 1.56, 95% CI 1.22 to 1.99). In addition to type of anticoagulant, prior liver, gallbladder and kidney disease, cancer, anaemia, heart failure and alcoholism significantly predicted liver injury hospitalisation. A predictive model including these variables had adequate discriminative ability (C-statistic 0.67, 95% CI 0.64 to 0.70). Conclusions: Among patients with non-valvular AF, DOACs were associated with lower risk of liver injury hospitalisation compared with warfarin, with dabigatran showing the lowest risk.