Abstract
The purpose of this study is to investigate the correlation between glomerular filtration rate (GFR) estimated by different renal function equations and non-vitamin K antagonist oral anticoagulant concentration. Atrial fibrillation patients who aged ≥ 20 years and used dabigatran, rivaroxaban, or apixaban for thromboembolism prevention were enrolled to collect blood samples and measure drug concentrations using ultra-high-performance liquid chromatography with tandem mass spectrometry. The GFR was estimated using the Cockroft–Gault formula (abbreviated as creatinine clearance, CrCL), Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) featuring both creatinine and cystatin C, and the Modification of Diet in Renal Disease Study equation (MDRD). Multivariate regression was used to investigate the associations of different renal function estimates with drug concentrations. A total of 511 participants were enrolled, including 146 dabigatran users, 164 rivaroxaban users and 201 apixaban users. Compared to clinical trials, 35.4% of dabigatran, 4.9% of rivaroxaban, and 5.5% of apixaban concentrations were higher than the expected range (p < 0.001). CKD-EPI and MDRD estimates classified fewer patients as having GFR < 50 mL/min than CrCL in all 3 groups. Both CrCL and CKD-EPI were associated with higher-than-expected ranges of dabigatran or rivaroxaban concentrations. Nevertheless, none of the renal function equations was associated with higher-than-expected apixaban concentrations. For participants aged ≥ 75 years, CKD-EPI may be associated with higher-than-expected trough concentration of dabigatran. In conclusion, CrCL and CKD-EPI both can be used to identify patients with high trough concentrations of dabigatran or rivaroxaban. Among elderly patients who used dabigatran, CKD-EPI may be associated with increased drug concentration.
Highlights
Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial have been approved by the Taiwanese Food and Drug Administration
The main purpose of our present study is to examine the correlation between Direct oral anticoagulants (DOAC) concentration and the GFR estimated by different renal function equations, including the C–G formula; the CKD-EPI equation, which featured both CRE and cystatin C; and Modification of Diet in Renal Disease (MDRD) study equations and to investigate which estimation approach provides more precise identification of patients with increased drug concentrations
After excluding 2 participants with missing data for essential laboratory tests for GFR estimates, 1 participant who discontinued dabigatran for more than 3 days before drug level measurement, 2 participants in the rivaroxaban group who had no atrial fibrillation (AF) diagnosis, and 4 participants in the apixaban group who were on stable hemodialysis, 511 participants were included in the data analysis
Summary
Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial have been approved by the Taiwanese Food and Drug Administration. One New Zealand study showed that the CKD-EPI equation overestimated the dabigatran dose compared to the C–G formula and caused an increased risk of hemorrhagic events[24] Another Taiwanese study showed that both the CKD-EPI and MDRD study equations overestimated GFR, led to inappropriate DOAC doses, and further attenuated the benefit of DOAC compared with warfarin in reducing major b leeding[25]. The main purpose of our present study is to examine the correlation between DOAC concentration and the GFR estimated by different renal function equations, including the C–G formula; the CKD-EPI equation, which featured both CRE and cystatin C; and MDRD study equations and to investigate which estimation approach provides more precise identification of patients with increased drug concentrations
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