Different renal function estimation formulae and implications for dosing and clinical outcomes when prescribing non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

Abstract

Abstract Background Pivotal randomized trials of non-vitamin K antagonist oral anticoagulants (NOACs) adopted Cockcroft-Gault (CG) formula to calculate estimated glomerular filtration rate (eGFR) to determine the dosages of NOACs. However, Modified Diet in Renal Disease (MDRD]) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae are commonly used in clinical practice. In the present study, we investigated the agreements/disagreements of eGFRs calculated using different equations in Asian AF patients. Second, we studied the impacts of using different equations on the dosages of NOACs used, and finally, clinical outcomes compared to warfarin were assessed. Methods This retrospective study used medical data from a multicenter healthcare provider in Taiwan which included 39,239 AF patients whose data about body weight (BWs) and serum Creatinine (sCr) were available. Among these patients, there were 11,185 and 2,323 AF patients treated with NOACs and warfarin, respectively. Results At the cutoff values of eGFR of <15 mL/min, 15–50 mL/min and >50 mL/min, the agreements were 78% between MDRD and CG, and 81% between CKD-EPI and CG. The disagreements between different equations were largely due to over-estimations (21% for MDRD and 17% for CKD-EPI), especially for patients aged >75 years and BWs <50kg (58.8% for MDRD and 50.9% for CKD-EPI). For patients treated with NOACs, around 7.6% (MDRD) and 6.5% (CKD-EPI) had dosages of NOACs that were discordant compared to using the CG equation, with the highest percentages for rivaroxaban (11–13%) and lowest for edoxaban (1%). Among patients receiving NOACs whose dosages were defined as “on-label” based on MDRD or CKD-EPI, only those whose dosages were “truly on-label” based on CG were associated with a lower risk of ischemic stroke/systemic embolism (IS/SE) (adjusted hazard ratio [aHR] 0.78, 95% CI 0.61–1.00), major bleeding (aHR 0.34, 95% CI 0.26–0.45) and IS/SE or major bleeding (aHR 0.55, 95% CI 0.46–0.66) compared to warfarin (Figure). The risk of IS/SE (aHR 0.82, 95% CI 0.39–1.72), major bleeding (aHR 0.57, 95% CI 0.25–1.32) and IS/SE or major bleeding (aHR 0.69, 95% CI 0.40–1.19) were similar between warfarin and patients treated with NOACs whose dosages were disconcordant between eGFRs calculated using MDRD and CG (Figure). Conclusions The adoptions of MDRD or CKD-EPI rather than CG would result in inappropriate dosing of NOACs (mainly overdosing) which would attenuate the advantages of NOACs compared to warfarin. Therefore, the CG equation should be used as the “gold standard” for the calculations of eGFRs to guide the NOAC dosages. Funding Acknowledgement Type of funding source: None