Variability in Non–Vitamin K Antagonist Oral Anticoagulants Dose Adjustment in Atrial Fibrillation Patients With Renal Dysfunction: The Influence of Renal Function Estimation Formulae

Abstract Background Non-vitamin K antagonist oral anticoagulants (NOACs) require renal dose adjustment. The most common estimates of renal function in clinical practice are derived from glomerular filtration rate (eGFR; Modified Diet in Renal Disease [MDRD] or the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). However, the landmark stroke prevention trials and product monographs recommend the use of the Cockcroft-Gault creatinine clearance equation (eCrCl) for drug eligibility and dose adjustment. We sought to evaluate the agreement in NOAC dosing between these three equations in a large population of patients with AF and moderate chronic kidney disease (CKD). Methods We identified 831 patients with non-dialysis dependent CKD and AF (CHA 2 DS 2 -VASc 3.9). For each patient eCrCl, MDRD eGFR, and CKD-EPI eGFR were prospectively calculated. Eligibility criteria for NOAC medications were evaluated by comparing the eGFR as estimated by MDRD or CKD-EPI equation to the eCrCl as estimated by Cockcroft-Gault, with the latter regarded as the "gold standard." Results The use of eGFR resulted in significant misclassification with respect to NOAC dosing. Compared to eCrCl the MDRD eGFR and CKD-EPI eGFR misclassified 36.2% and 35.8% of patients, respectively. The misclassification resulted in under-treatment (e.g. inappropriate dose reduction; 26.9% MDRD, 28.8% CKD-EPI), and to a lesser extent over-treatment (e.g. inappropriate use of standard dose; 9.3% MDRD, 7.0% CKD-EPI). Conclusion MDRD and CKD-EPI eGFR fails to correctly identify a significant proportion of patients that require NOAC dose adjustment, limiting their clinical utility. Cockcroft-Gault eCrCl should be calculated for all patients in whom a NOAC is being prescribed.