Author + information
- Xiaoxi Yao, PhD∗ (, )
- Nilay D. Shah, PhD,
- Lindsey R. Sangaralingham, MPH,
- Bernard J. Gersh, MB, ChB, DPhil and
- Peter A. Noseworthy, MD
- ↵∗Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
We thank Drs. Schwartz, Pazmiño, and Shroff for their interest in our paper (1). We agree that there is a difference between estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and creatinine clearance using the Cockcroft-Gault method. Due to the lack of body weight, our study only used the CKD-EPI equation, but we do not believe this substantially affected our findings.
The rationale behind dose reduction is that non-vitamin K antagonist oral anticoagulants (NOACs) rely on renal function for drug elimination; thus, patients with reduced renal function should receive a reduced dose. In theory, the dose reduction should rely on the most accurate estimate of renal function; however, the Cockcroft-Gault equation was developed before standardization of creatinine assays and cannot be re-expressed for use with standardized creatinine assay (2). The CKD-EPI equation was found to be more accurate than the Cockcroft-Gault method, and is recommended by the current kidney guidelines for evaluating renal function (2). The drug labels use creatinine clearance, because this method was used in the trials, which were designed before the CKD-EPI equation was developed and widely adopted, not because the Cockcroft-Gault method leads to better dosing decisions. The National Institute of Diabetes and Digestive and Kidney Diseases suggests that either equation can be used for general drug dosing purpose (3). The 2011 Kidney Disease Improving Global Outcomes clinical update on drug dosing in patients with kidney diseases recommended using the most accurate method for estimating renal function when making dosing decisions, rather than limiting it to the Cockcroft-Gault equation (4).
We currently face the challenge that the dosage advice in drug labels has not caught up with what is now standard practice. Future studies are needed to compare clinical outcomes using the 2 equations for dosing. Fortunately, for most patients, the dosing decision would be the same using either equation. However, for patients whose indication for dose reduction depends on which equation is used, clinicians should carefully consider other factors when making decisions, such as drug interaction, stroke, and bleeding as risk factors, as well as patient preference.
Chronic kidney disease (CKD) stages may not be very useful for NOAC dosing, as the glomerular filtration rate cutoff points for NOAC dose reduction and CKD stages are often different. Furthermore, CKD diagnosis requires an evaluation of chronicity, and ongoing dose adjustments may be needed in patients with brief periods of renal dysfunction or fluctuating renal function.
Please note: Dr. Gersh serves on the data and safety monitoring board for Mount Sinai St. Lukes, Boston Scientific Corporation, St. Jude Medical Inc., Janssen Research & Development, Baxter Healthcare Corporation, Cardiovascular Research Foundation, and Thrombosis Research Institute; serves on the advisory board for Medtronic Inc.; and provides general consulting for Janssen Scientific Affairs (formerly known as Ortho-McNeil), Xenon Pharmaceuticals, Cipla Limited, and Armetheon Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2017 American College of Cardiology Foundation
- Yao X.,
- Shah N.D.,
- Sangaralingham L.R.,
- Gersh B.J.,
- Noseworthy P A.
- ↵The National Institute of Diabetes and Digestive and Kidney Diseases. Estimation of Kidney Function for Prescription Medication Dosage in Adults. 2015. Available: http://www.niddk.nih.gov/health-information/health-communication-programs/nkdep/a-z/ckd-drug-dosing/Pages/CKD-drug-dosing.aspx. Accessed August 21, 2017.