Oral anticoagulant treatment and risk of kidney disease-a nationwide, population-based cohort study

Ane Emilie Friis Vestergaard; Simon Kok Jensen; Uffe Heide-Jørgensen; Kasper Adelborg; Henrik Birn; Juan-Jesus Carrero; Christian Fynbo Christiansen

doi:10.1093/ckj/sfad252

Oral anticoagulant treatment and risk of kidney disease-a nationwide, population-based cohort study

Clin Kidney J. 2023 Oct 3;17(1):sfad252. doi: 10.1093/ckj/sfad252. eCollection 2024 Jan.

Authors

Ane Emilie Friis Vestergaard¹, Simon Kok Jensen¹, Uffe Heide-Jørgensen¹, Kasper Adelborg^{1

2}, Henrik Birn^{3

4}, Juan-Jesus Carrero⁵, Christian Fynbo Christiansen¹

Affiliations

¹ Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark.
² Department of Clinical Biochemistry, Gødstrup Regional Hospital, Gødstrup, Denmark.
³ Departments of Biomedicine and Clinical Medicine, Aarhus University, Aarhus, Denmark.
⁴ Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.
⁵ Department of Medical Epidemiology and Biostatisctics, Karolinska Institutet, Stockholm, Sweden.

Abstract

Background: Direct oral anticoagulants (DOACs) are recommended as first-line treatment of atrial fibrillation. Whether DOAC use is associated with lower risks of kidney complications compared with vitamin K antagonists (VKAs) remains unclear. We examined this association in a nationwide, population-based cohort study.

Methods: We conducted a cohort study including patients initiating oral anticoagulant treatment within 3 months after an atrial fibrillation diagnosis in Denmark during 2012-18. Using routinely collected creatinine measurements from laboratory databases, we followed patients in an intention-to-treat approach for acute kidney injury (AKI) and chronic kidney disease (CKD) progression. We used propensity-score weighting to balance baseline confounders, computed weighted risks and weighted hazard ratios (HRs) with 95% confidence intervals (CIs) comparing DOACs with VKAs. We performed several subgroup analyses and a per-protocol analysis.

Results: We included 32 781 persons with atrial fibrillation initiating oral anticoagulation (77% initiating DOACs). The median age was 75 years, 25% had a baseline estimated glomerular filtration rate <60 mL/min/1.73 m², and median follow-up was 2.3 (interquartile range 1.1-3.9) years. The weighted 1-year risks of AKI were 13.6% in DOAC users and 15.0% in VKA users (HR 0.86, 95% CI 0.82; 0.91). The weighted 5-year risks of CKD progression were 13.9% in DOAC users and 15.4% in VKA users (HR 0.85, 95% CI 0.79; 0.92). Results were similar across subgroups and in the per-protocol analysis.

Conclusions: Initiation of DOACs was associated with a decreased risk of AKI and CKD progression compared with VKAs. Despite the potential limitations of observational studies, our findings support the need for increased clinical awareness to prevent kidney complications among patients who initiate oral anticoagulants.

Keywords: acute kidney injury; anticoagulant drugs; atrial fibrillation; pharmacoepidemiology; renal insufficiency.