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Prospective study of oral anticoagulants and risk of liver injury in patients with atrial fibrillation
  1. Alvaro Alonso1,
  2. Richard F MacLehose2,
  3. Lin Y Chen3,
  4. Lindsay GS Bengtson4,
  5. Alanna M Chamberlain5,
  6. Faye L Norby2,
  7. Pamela L Lutsey2
  1. 1Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
  2. 2Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
  3. 3Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
  4. 4Health Economics and Outcomes Research, Life Sciences, Optum, Eden Prairie, Minnesota, USA
  5. 5Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to Dr Alvaro Alonso, Department of Epidemiology, Rollins School of Public Health, Emory University. 1518 Clifton Rd NE, CNR Room 3051, Atlanta, GA 30322, USA; alvaro.alonso{at}


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.

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  • Contributors All authors contributed to the study design, analysis, interpretation of results and drafting of the manuscript.

  • Funding American Heart Association 16EIA26410001. U.S. Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute R01-HL122200.

  • Competing interests AA had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. LGSB is an employee of Optum.

  • Ethics approval Emory University Institutional Review Board (IRB), University of Minnesota IRB.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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