Exposure to vitamin k antagonists and kidney function decline in patients with atrial fibrillation and chronic kidney disease

Abstract

BackgroundExposure to vitamin K antagonists (VKA) has been suggested to accelerate progression of chronic kidney disease (CKD) but robust clinical data are currently lacking. MethodsWe retrospectively evaluated the impact of VKA exposure on kidney function in patients with atrial fibrillation (AF) and CKD stage 3/4. Patients were prospectively followed within a primary care electronic database (median follow‐up of 1.45 years). The kidney function trajectory over time, defined as the annualized change in estimated glomerular filtration rate (eGFR), was analyzed with linear mixed‐effects regression including propensity score adjustment. Results14 432 patients (median age 78 years, median CHA2DS2‐VASc score 4 points) contributed 97 792 eGFR measurements (mean 6.8 measurements/patient; range: 1‐197). Mean baseline eGFR was 50.3 mL/min/1.73 m2; and declined by 1.10 mL/min/1.73 m2/year (95% CI: 0.91‐1.28, P<0.0001). In 7409 patients with VKA exposure, CKD progression was significantly faster compared to patients without VKA exposure (5‐year absolute eGFR loss from baseline: 6.0 mL/min/1.73 m2 vs 4.5 mL/min/1.73 m2, for an absolute 5‐year excess eGFR decline with VKA exposure of 1.5 mL/min/1.73 m2 (95% CI: 0.4‐2.7, P = 0.002). These results prevailed upon adjusting for CHA2DS2‐VASc score and other potential imbalances in prognostic variables, and in several sensitivity analyses. In the group without documented VKA exposure, 1775 VKA patients (24%) and 1012 patients (14%) developed a 30% decline in eGFR during follow‐up (P<0.0001). ConclusionsIn patients with AF and CKD, VKA use is associated with accelerated eGFR decline. Within the limitations of a retrospective analysis, this finding supports the “VKA‐renal‐calcification hypothesis.” However, although statistically significant, the excess loss in eGFR over 5 years with VKA was modest.