Potential risks of substituting estimated glomerular filtration rate for estimated creatinine clearance for dosing of direct oral anticoagulants in atrial fibrillation and chronic kidney disease

Abstract

Abstract Background In the clinical trials with direct oral anticoagulants (DOAC) estimates of creatinine clearance (CrCl) with Cockcroft-Gault equation were used to assess renal functions. Recently, most laboratories report renal function estimated with the Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, which may lead to impaired dosing of DOACs by physicians. Purpose To compare estimated glomerular filtration rate and estimated creatinine clearance in a large group of patients with atrial fibrillation and chronic kidney disease. Methods Physicians from 423 institutions in the Czech Republic were asked to enroll 5 consecutive outpatients with atrial fibrillation (AF) treated by a DOAC with stage 3 chronic kidney disease and glomerular filtration rate (eGFR) 30–59 ml/min estimated by MDRD or CKD EPI equations into the registry. Besides eGFR, serum creatinine values were recorded and CrCl calculated by the Cockroft-Gault formula. Results of CrCl and eGFR obtained in individual patients were compared and statistically analyzed using two-sample t-test. Results A total of 2115 patients were enrolled. Mean CrCl was 47.43 ml/min, mean eGFR calculated by MDRD and CKD-EPI was lower 43.88 and 43.53 ml/min (P for difference <0.001 for both). Mean difference between CrCl and eGFR in individual patients calculated by MDRD and CKD-EPI was 8.8 and 9.41 ml/min. A difference beween CrCl and eGFR >10 ml/min was found in 31.5% and 34.8% patients when using MDRD and CKD-EPI formulas. The respective differences between CrCl and eGFR between 4.1 and 10 ml/min were found in 28.5% (MDRD) and 30.8% (CKD-EPI). At CrCl above or below 50 ml/min, 24.0% and 24.2% were misclassified when using eGFR calculated by MDRD and CKD-EPI. At CrCl above or below 30 ml/min, 9.8% (MDRD) and 10.0% (CKD-EPI) patients were misclassified (please see Figures). Conclusions When eGFR estimated by MDRD or CKD-EPI is used to assess renal function and guide DOAC dosing instead of CrCl calculated by the Cockroft-Gault formula in patients with AF and stage 3 CKD, more than a third of patients is misclassified and wrong DOAC dose can be recommended. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boehringer-Ingelheim Differences between CrCl and CKD-EPIDifferences between CrCl and MDRD