Interaction of Kidney Function and Dapagliflozin in Patients With Acute Heart Failure: A Pre-Specified Analysis of DICTATE-AHF

BACKGROUND Early sodium glucose co-transporter 2 inhibitor initiation during acute heart failure (AHF) acutely improves measures of diuresis. Glucosuria from dapagliflozin decreases with declining estimated glomerular filtration rate (eGFR), and thus, the decongestive benefits may differ across eGFR. We investigated dapagliflozin's acute diuretic effects according to eGFR at randomization and the effects of dapagliflozin initiation on kidney function in AHF. METHODS This pre-specified analysis of DICTATE-AHF evaluated 238 patients randomized within 24 hours of AHF hospital admission to dapagliflozin 10 mg daily or structured usual care, with protocolized IV diuretics in both groups. The role of eGFR at randomization as an effect modifier between weight loss, diuresis, and natriuresis per 40 mg IV furosemide and treatment assignment and changes in kidney function were assessed using proportional odds models. RESULTS Median (IQR) eGFR at randomization was 53 (42 to 70) mL/min/1.73 m2. eGFR at randomization did not modify dapagliflozin's treatment effect on diuretic efficiency assessed by weight loss (interaction p = 0.22), diuresis (interaction p = 0.23), or natriuresis (interaction p = 0.36). Dapagliflozin was not associated with a decrease in eGFR (p = 0.89), blood urea nitrogen (BUN) (p = 0.94), nor BUN/serum creatinine ratio (p = 0.41) from randomization to end-of-study. CONCLUSIONS Early dapagliflozin initiation during AHF hospitalization is safe and similarly effective on acute diuretic measures across a wide range of eGFR. eGFR did not modify dapagliflozin's effects on weight loss, diuresis, and natriuresis. Dapagliflozin was not associated with worsening kidney function. TRIAL REGISTRATION NCT04298229.