Anticoagulant Therapy and Risk of Kidney Disease - A Nationwide Cohort Study

Background: Vitamin K-antagonists (VKAs) and direct oral anticoagulants (DOACs) are widely used in the treatment of atrial fibrillation and venous thromboembolism. Recent studies indicate that anticoagulant therapy may be associated with kidney complications with lower risks related to DOACs compared with VKAs. However, these studies suffer from methodological limitations, which we aim to address using the unique Danish setting of population-based medical databases.

Objectives: To examine the risk of acute kidney injury (AKI) and chronic kidney disease (CKD) progression in patients initiating DOACs and VKAs.

Methods: We conducted a new user active comparator cohort study in patients who started oral anticoagulant drug use within three months after an atrial fibrillation diagnosis during 2012 to 2018. Using routinely collected creatinine measurements from laboratory databases, we followed patients in an intension-to-treat approach for AKI and CKD progression. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria; CKD progression was a composite of >30% decline in estimated glomerular filtration rate (eGFR) or kidney failure. Propensity-score weighting was used to balance baseline confounders; we reported weighted absolute risks using the Aalen-Johansen estimator and weighted hazard ratios (HRs) using Cox regression. Consistency was checked within prespecified subgroups.

Results: We included 33,670 persons with atrial fibrillation initiating oral anticoagulation with 77% in the DOAC cohort. The median age was 75 years, 48% were women, and 25% had a baseline eGFR <60 ml/min/1.73 m2. The median follow-up was 2.3 years. Absolute risks of kidney complications were high: During the first year of treatment the cumulative risk of AKI was 13.9% in the DOAC group and 15.5% in the VKA group; the 5-year risk of CKD progression was 14.0% in DOAC users and 15.4% in VKA users. Compared to VKA initiation, DOAC treated patients had lower rates of both AKI and CKD progression with HRs of 0.85 (95% CI [0.81; 0.89]) and 0.84 (95% CI [0.78; 0.91]) respectively. Results were similar across subgroups of age, sex, baseline eGFR, and diabetes.

Conclusions: Kidney complications were common among atrial fibrillation patients initiating oral anticoagulant drugs. DOAC initiators had lower absolute risks and corresponding lower rates of AKI and CKD progression than initiators of VKAs.