Abstract 13678: Initial Decline in Estimated Glomerular Filtration Rate After Initiation of Dapagliflozin in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: Insights From DELIVER

Abstract

Introduction: Among patients with heart failure with reduced ejection fraction, an initial eGFR decline >10% with dapagliflozin was associated with a lower risk of cardiovascular (CV) outcomes and slowing of kidney function decline, compared with a similar decline among those on placebo. We examined these associations in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). Methods: In this prespecified analysis of DELIVER, the frequency of initial eGFR decline (baseline to month 1) was compared between dapagliflozin vs. placebo. Cox models (adjusted for baseline eGFR, age, sex, race, BMI, hypertension, left ventricular ejection fraction, log-transformed NT-proBNP, systolic blood pressure (SBP), ACEi or ARB use, MRA use, and change in SBP from baseline to month 1) were fit to estimate the association of initial >10% eGFR decline with CV (CV death or heart failure event) and kidney (≥50% eGFR decline, eGFR <15 ml/min/1.73m 2 or dialysis, death from renal causes) outcomes, landmarked at month 1, stratified by baseline diabetes. Results: The median [IQR] initial change in eGFR was -1 [-6, +5] and -4 [-9, +1] ml/min/1.73m 2 with placebo and dapagliflozin, respectively (difference 3 ml/min/1.73m 2 ; P<0.001). Patients randomized to dapagliflozin were more likely to develop an initial eGFR decline >10%, vs. placebo (odds ratio 1.9; 95%CI 1.7, 2.1). An initial eGFR decline >10% was associated with a higher risk of the CV outcome among those randomized to placebo (adjusted hazard ratio [aHR] 1.31; 95%CI 1.08, 1.59), but not to dapagliflozin (aHR 0.93; 95%CI 0.77, 1.13; P interaction =0.01; Fig. 1 ). In the dapagliflozin group, an initial eGFR decline >10% was not associated with adverse kidney outcomes (aHR 0.94; 95%CI 0.49, 1.82). Conclusions: Among patients with HFmrEF/HFpEF in DELIVER, an initial eGFR decline >10% (vs. ≤10%) was not associated with a higher risk of cardiovascular or kidney events, among those assigned to dapagliflozin.