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American Journal of Kidney Diseases

Apixaban Dosing Patterns Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation Receiving Dialysis: A Retrospective Cohort Study

  • James B. Wetmore
    Correspondence
    Address for Correspondence: James B. Wetmore, MD, MS, Chronic Disease Research Group, Hennepin Healthcare Research Institute, 701 Park Ave, Suite S4.100, Minneapolis, MN 55415.
    Affiliations
    Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, Minnesota

    Division of Nephrology, University of Minnesota, Minneapolis, Minnesota
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  • Eric D. Weinhandl
    Affiliations
    Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, Minnesota

    Hennepin County Medical Center and Department of Medicine, and Department of Pharmaceutical Care and Health Systems, University of Minnesota, Minneapolis, Minnesota
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  • Heng Yan
    Affiliations
    Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, Minnesota
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  • Jorge L. Reyes
    Affiliations
    Department of Internal Medicine, Hennepin County Medical Center, Minneapolis, Minnesota
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  • Charles A. Herzog
    Affiliations
    Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, Minnesota

    Division of Cardiology, University of Minnesota, Minneapolis, Minnesota
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  • Nicholas S. Roetker
    Affiliations
    Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, Minnesota
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Published:April 22, 2022DOI:https://doi.org/10.1053/j.ajkd.2022.03.007

      Background & Objectives

      Comparison of clinical outcomes across anticoagulation regimens using different apixaban dosing or warfarin is not well-defined in patients with nonvalvular atrial fibrillation (AF) who are receiving dialysis. This study compared these outcomes in a US national cohort of patients with kidney failure receiving maintenance dialysis.

      Study Design

      Retrospective cohort study.

      Setting & Participants

      Patients receiving dialysis represented in the US Renal Data System database 2013-2018 who had AF and were treated with apixaban or warfarin.

      Exposure

      First prescribed treatment with apixaban dosed according to the label, apixaban dosed below the label, or warfarin.

      Outcome

      Ischemic stroke/systemic embolism, major bleeding, and all-cause mortality.

      Analytical Approach

      Cox proportional hazards models with inverse probability of treatment weighting. Analyses simulating an intention-to-treat (ITT) approach as well as those incorporating censoring at drug switch or discontinuation (CAS) were also implemented. Inverse probability of censoring weighting was used to account for possible informative censoring.

      Results

      Among 17,156 individuals, there was no difference in risk of stroke/systemic embolism among the label-concordant apixaban, below-label apixaban, and warfarin treatment groups. Both label-concordant (HR, 0.67 [95% CI, 0.55-0.81]) and below-label (HR, 0.68 [95% CI, 0.55-0.84]) apixaban dosing were associated with a lower risk of major bleeding compared with warfarin in ITT analyses. Compared with label-concordant apixaban, below-label apixaban was not associated with a lower bleeding risk (HR, 1.02 [95% CI, 0.78-1.34]). In the ITT analysis of mortality, label-concordant apixaban dosing was associated with a lower risk versus warfarin (HR, 0.85 [95% CI, 0.78-0.92]) while there was no significant difference in mortality between below-label dosing of apixaban and warfarin (HR, 0.97 [95% CI, 0.89-1.05]). Overall, results were similar for the CAS analyses.

      Limitations

      Study limited to US Medicare beneficiaries; reliance on administrative claims to ascertain outcomes of AF, stroke, and bleeding; likely residual confounding.

      Conclusions

      Among patients with nonvalvular AF undergoing dialysis, warfarin is associated with an increased risk of bleeding compared with apixaban. The risk of bleeding with below-label apixaban was not detectably less than with label-concordant dosing. Label-concordant apixaban dosing is associated with a mortality benefit compared to warfarin. Label-concordant dosing, rather than reduced-label dosing, may offer the most favorable benefit-risk trade-off for dialysis patients with nonvalvular AF.

      Graphical abstract

      Index Words

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