The risk of acute kidney injury with oral anticoagulants in elderly adults with atrial fibrillation

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

Methods — A population-based cohort study of 20,683 outpatients in Ontario, Canada, ≥66 years, with atrial fibrillation who were prescribed warfarin, dabigatran, rivaroxaban or apixaban between 2009- 2017. Inverse probability of treatment weighting based on derived propensity scores for the treatment with each DOAC was used to balance baseline characteristics among patients receiving each of the three DOACs, compared to 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 DOACs. The primary outcome was a hospital encounter with AKI, defined using KDIGO thresholds. Prespecified subgroup analyses were conducted by estimated glomerular filtration rate (eGFR) category, and by the percentage of international normalized ratio measurements in range, a validated marker of anticoagulation control.

Results — Each DOAC was associated with a significantly lower risk of AKI compared to warfarin (weighted HR 0.65; 95% CI 0.53 to 0.80 for dabigatran, weighted HR 0.85; 95% CI 0.73 to 0.98 for rivaroxaban; and weighted HR 0.81; 95% CI 0.72 to 0.93 for apixaban). In subgroup analysis, the lower risk of AKI associated with each DOAC was consistent across each eGFR strata. The risk of AKI was significantly lower among users of each of the DOACs compared to warfarin users who had a percentage of international normalized ratio measurements ≤56.1%.

Conclusions — DOACs were associated with a lower risk of AKI compared to warfarin.