(P091) VARIABILITY IN NOAC DOSE ELIGIBILITY AND ADJUSTMENT ACCORDING TO RENAL FORMULAE AND CLINICAL OUTCOMES IN AF PATIENTS WITH AND WITHOUT CKD: INSIGHTS FROM ORBIT AF II

Background: Non-Vitamin K Oral Anticoagulants (NOACs) are used for prevention of thromboembolism in patients with atrial fibrillation (AF). Guidelines recommend dose adjustment based on kidney function.The most common estimates of kidney function employed in clinical practice are derived from glomerular filtration rate (eGFR), however, product monographs recommend the use of the Cockcroft-Gault creatinine clearance equation (eCrCl) for dose adjustment. We sought to evaluate misclassification of NOAC renal dosing using eGFR versus eCrCl.

METHODS AND RESULTS: We included patients enrolled in Outcomes Registry for Better Informed Treatment of Atrial Fibrillation AF II (ORBIT-AF II) trial. eGFR was calculated using both the Modified Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae. Dose adjustments and eligibility were based on landmark trials, with eCrCl of 30-50ml/min for rivaroxaban, eCrCl of 30ml/min for dabigatran, and eCrCl of 25 ml/min for apixaban. 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, new-onset heart failure (HF), and myocardial infarction. Sensitivity analysis was performed for the subgroup of patients with CKD (eCrCl < 60 ml/min.) Among 8,727 in the overall cohort (median age: 71 (64, 78); medianCHADS2score: 2), agreement between CrCl and eGFR(MDRD and CKD-EPI)was observed in 93.5-93.8% of patients. Among 2,184 patients with CKD, the agreement between eCrCl and eGFR (MDRD and CKD-EPI) 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].

Conclusion: 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.