The Risk of Acute Kidney Injury with Oral Anticoagulants in Elderly Adults with Atrial Fibrillation

Ziv Harel; Eric McArthur; Nivethika Jeyakumar; Manish M. Sood; Amit X. Garg; Samuel A. Silver; Paul Dorian; Daniel Blum; William Beaubien-Souligny; Andrew T. Yan; Sunil V. Badve; Brendan Smyth; Min Jun; Racquel Jandoc; Abhijat Kitchlu; Ron Wald

doi:10.2215/CJN.05920421

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Abstract

Background and objectives Anticoagulation with either a vitamin K antagonist or a direct oral anticoagulant may be associated with AKI. Our objective was to assess the risk of AKI among elderly individuals with atrial fibrillation newly prescribed a direct oral anticoagulant (dabigatran, rivaroxaban, or apixaban) versus warfarin.

Design, setting, participants, & measurements Our population-based cohort study included 20,683 outpatients in Ontario, Canada, ≥66 years with atrial fibrillation who were prescribed warfarin, dabigatran, rivaroxaban, or apixaban between 2009 and 2017. Inverse probability of treatment weighting on the basis of derived propensity scores for the treatment with each direct oral anticoagulant was used to balance baseline characteristics among patients receiving each of the three direct oral anticoagulants compared with warfarin. Cox proportional hazards regression was performed in the weighted population to compare the association between the prescribed anticoagulant and the outcomes of interest. The exposure was an outpatient prescription of warfarin or one of the direct oral anticoagulants. The primary outcome was a hospital encounter with AKI, defined using Kidney Disease Improving Global Outcomes thresholds. Prespecified subgroup analyses were conducted by eGFR category and by the percentage of international normalized ratio measurements in range, a validated marker of anticoagulation control.

Results Each direct oral anticoagulant was associated with a significantly lower risk of AKI compared with warfarin (weighted hazard ratio, 0.65; 95% confidence interval, 0.53 to 0.80 for dabigatran; weighted hazard ratio, 0.85; 95% confidence interval, 0.73 to 0.98 for rivaroxaban; and weighted hazard ratio, 0.81; 95% confidence interval, 0.72 to 0.93 for apixaban). In the subgroup analysis, the lower risk of AKI associated with each direct oral anticoagulant was consistent across each eGFR strata. The risk of AKI was significantly lower among users of each of the direct oral anticoagulants compared with warfarin users who had a percentage of international normalized ratio measurements ≤56%.

Conclusions Direct oral anticoagulants were associated with a lower risk of AKI compared with warfarin.

Received April 30, 2021.
Accepted August 9, 2021.

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