Jason G Andrade1, Nathaniel M Hawkins2, Christopher B Fordyce2, Marc W Deyell2, Lee Er3, Ognjenka Djurdjev3, Laurent Macle4, Sean A Virani2, Adeera Levin5. 1. Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Electrophysiology Service at the Montreal Heart Institute and the Department of Medicine, Université de Montréal, Montreal, Quebec, Canada. Electronic address: Jason.andrade@vch.ca. 2. Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. 3. Department of Methodology and Analytics, BC Provincial Renal Agency, Vancouver, British Columbia, Canada. 4. Electrophysiology Service at the Montreal Heart Institute and the Department of Medicine, Université de Montréal, Montreal, Quebec, Canada. 5. Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
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 estimated 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 3 equations in a large population of patients with atrial fibrillation and moderate chronic kidney disease. METHODS: We identified 831 patients with non-dialysis-dependent chronic kidney disease and atrial fibrillation (CHA2DS2-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 with 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 with eCrCl, the MDRD eGFR and CKD-EPI eGFR misclassified 36.2% and 35.8% of patients, respectively. The misclassification resulted in undertreatment (eg, inappropriate dose reduction; 26.9% MDRD, 28.8% CKD-EPI), and to a lesser extent overtreatment (eg, inappropriate use of standard dose; 9.3% MDRD, 7.0% CKD-EPI). CONCLUSIONS: MDRD and CKD-EPI eGFR fail to correctly identify a significant proportion of patients who require NOAC dose adjustment, limiting their clinical utility. Cockcroft-Gault eCrCl should be calculated for all patients in whom a NOAC is being prescribed.
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 estimated 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 3 equations in a large population of patients with atrial fibrillation and moderate chronic kidney disease. METHODS: We identified 831 patients with non-dialysis-dependent chronic kidney disease and atrial fibrillation (CHA2DS2-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 with 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 with eCrCl, the MDRD eGFR and CKD-EPI eGFR misclassified 36.2% and 35.8% of patients, respectively. The misclassification resulted in undertreatment (eg, inappropriate dose reduction; 26.9% MDRD, 28.8% CKD-EPI), and to a lesser extent overtreatment (eg, inappropriate use of standard dose; 9.3% MDRD, 7.0% CKD-EPI). CONCLUSIONS: MDRD and CKD-EPI eGFR fail to correctly identify a significant proportion of patients who require NOAC dose adjustment, limiting their clinical utility. Cockcroft-Gault eCrCl should be calculated for all patients in whom a NOAC is being prescribed.
Authors: Morten Baltzer Houlind; Kristian Kjær Petersen; Henrik Palm; Lillian Mørch Jørgensen; Mia Aakjær; Lona Louring Christrup; Janne Petersen; Ove Andersen; Charlotte Treldal Journal: Pharmaceuticals (Basel) Date: 2018-09-18