Abstract 9317: Variability in Non-Vitamin K Oral Anticoagulant Dose Adjustment According to Renal Formulae and Clinical Outcomes in Atrial Fibrillation Patients: Insights From ORBIT-AF II

Abstract

Background: Non-Vitamin K Oral Anticoagulants (NOACs) require dose adjustment based on kidney function. Glomerular filtration rate (eGFR) is most commonly used in clinical practice, but product monographs recommend the use of Cockcroft-Gault creatinine clearance equation (eCrCl) for dose adjustment. We sought to evaluate misclassification of NOAC renal dosing using eGFR versus eCrCl. Methods: We included patients enrolled in the ORBIT-AF II trial. eGFR was calculated using both the MDRD and CKD-EPI formulae. Dose adjustments and eligibility were based on landmark trials. Dosing was considered inappropriate when use of eGFR resulted in a lower (under-treatment) or higher (over-treatment) dose than that recommended by eCrCl. Agreement in NOAC dosing between eCrCl and eGFR was assessed. The primary outcome of major adverse cardiovascular and neurological events (MACNE) was a composite of cardiovascular death, stroke or systemic embolism, and myocardial infarction. Sensitivity analysis was performed for the subgroup of patients with CKD (eCrCl<60 ml/min). Results: Among 8,727 in the overall cohort, agreement between CrCl and eGFR was observed in 93.5-93.8% of patients. Among 2,184 patients with CKD, the agreement between eCrCl and eGFR was 79.9-80.7%. Dosing misclassification was observed in 11.5% of rivaroxaban and 1.1% of dabigatran and apixaban treated patients. Patients receiving an inappropriate NOAC dose had a lower mean eCrCl and eGFR. Undertreated patients were older and of lower body weight compared to overtreated and appropriately dosed patients. Dosing misclassification was more frequent in the CKD population (41.9% of rivaroxaban, 5.7% of dabigatran and 4.6% apixaban patients). At one-year, undertreated patients in the CKD group had significantly greater MACNE [adjusted HR 2.90 (1.09-7.75) compared to appropriate NOAC dosing group p = 0.03]. Conclusions: The prevalence of NOAC dosing misclassification NOACs was high when using eGFR, particularly among those with CKD. Among patients with CKD, potential undertreatment due to inappropriate and off-label renal formulae may result in worse clinical outcomes. These findings highlight the importance of using eCrCl, and not eGFR, for dose-adjustment in all AF patients receiving NOACs.