Comparative Risk of Acute Kidney Injury with Oral Anticoagulant Use Among Patients with Nonvalvular Atrial Fibrillation

Background: Acute kidney injury (AKI) is common in patients with nonvalvular atrial fibrillation (NVAF) taking oral anticoagulants (OAC), especially in those with underlying chronic kidney disease (CKD). However, little is known on the comparative risk of AKI with the use of different OAC, including the direct acting oral anticoagulants (DOACs).

Methods: We conducted a population-based cohort study using the administrative healthcare databases of Quebec, Canada. Patients with NVAF who were new users of oral anticoagulants between 2011 and 2014 were followed for hospitalized AKI, stratified by CKD status. Hazard ratios (HR) and corresponding 95% CI for hospitalized AKI with the use of dabigatran, rivaroxaban, and apixaban versus warfarin and versus each other in pairwise analyses, were assessed using Cox proportional hazards models. Estimates were stratified by the deciles of a disease risk score for AKI obtained from a historic cohort of 25,513 warfarin users with NVAF. The disease risk score included important demographic and clinical covariates weighted by their association with AKI.

Results: Our cohort of 26,357 patients with NVAF included 22,084 without, and 4273 with CKD. The rates of AKI hospitalization were 3.2 (95% CI 2.9-3.4) and 16.5 (95% CI 15.3-17.9) per 100 person-years, respectively. Among patients without CKD, apixaban (HR, 0.25; 95% CI, 0.14-0.44), rivaroxaban (HR, 0.50; 95% CI, 0.40-0.64), and dabigatran (HR, 0.68; 95% CI 0.57-0.81) were associated with a decreased risk of AKI compared with warfarin (Table 1). Similar findings were observed in the CKD cohort (Table 2). Compared with apixaban, dabigatran was associated with increased AKI risk in patients without (HR, 2.58; 95% CI, 1.42-4.67) and with (HR, 2.08; 95% CI, 1.01-4.26) CKD, as was rivaroxaban (without CKD - HR, 2.29 [95% CI, 1.24-4.20]; with CKD - HR, 1.98 [95% CI, 0.95-4.11]). Rivaroxaban was associated with decreased risk of AKI in patients without CKD (HR, 0.76; 95% CI, 0.58-0.99), compared with dabigatran.

Conclusions: Use of all DOACs was associated with decreased risk of AKI compared with warfarin. Apixaban was associated with the lowest comparative risk of AKI among DOACs, and rivaroxaban was suggested to be more protective than dabigatran in patients without CKD. While these findings await further confirmation, worsening renal function while on DOAC treatment has been associated with increased risk of major bleeding. Thus, suggested differences in the renal safety of DOACs should be incorporated in informed prescription and monitoring of these drugs.

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