Efficacy and Safety of Dapagliflozin in Patients With Acute Heart Failure.

Background: The primary goals during acute heart failure (AHF) hospitalization are decongestion and guideline-directed medical therapy (GDMT) optimization. Unlike diuretics or other GDMT, early dapagliflozin initiation could achieve both AHF goals.
Objectives: The authors aimed to assess the diuretic efficacy and safety of early dapagliflozin initiation in AHF.
Methods: In a multicenter, open-label study, 240 patients were randomized within 24 hours of hospital presentation for hypervolemic AHF to dapagliflozin 10 mg once daily or structured usual care with protocolized diuretic titration until day 5 or hospital discharge. The primary outcome, diuretic efficiency expressed as cumulative weight change per cumulative loop diuretic dose, was compared across treatment assignment using a proportional odds model adjusted for baseline weight. Secondary and safety outcomes were adjudicated by a blinded committee.
Results: For diuretic efficiency, there was no difference between dapagliflozin and usual care (OR: 0.65; 95% CI: 0.41-1.02; P = 0.06). Dapagliflozin was associated with reduced loop diuretic doses (560 mg [Q1-Q3: 260-1,150 mg] vs 800 mg [Q1-Q3: 380-1,715 mg]; P = 0.006) and fewer intravenous diuretic up-titrations (P ≤ 0.05) to achieve equivalent weight loss as usual care. Early dapagliflozin initiation did not increase diabetic, renal, or cardiovascular safety events. Dapagliflozin was associated with improved median 24-hour natriuresis (P = 0.03) and urine output (P = 0.005), expediting hospital discharge over the study period.
Conclusions: Early dapagliflozin during AHF hospitalization is safe and fulfills a component of GDMT optimization. Dapagliflozin was not associated with a statistically significant reduction in weight-based diuretic efficiency but was associated with evidence for enhanced diuresis among patients with AHF. (Efficacy and Safety of Dapagliflozin in Acute Heart Failure [DICTATE-AHF]; NCT04298229).
Competing Interests: Funding Support and Author Disclosures This study was funded by AstraZeneca as an investigator-initiated study. The authors designed the protocol, conducted the trial according to the protocol and statistical analysis plan, analyzed the data, and attest to the accuracy and completeness of the data. The REDCap database is supported by a grant from National Center for Advancing Translational Sciences/National Institutes of Health (NIH) (UL1 TR000445). Dr Cox has received research funding from AstraZeneca; and has received consulting fees from Roche and Translational Catalyst. Dr Collins has performed consulting for Boehringer Ingelheim, Reprieve Cardiovascular, Siemens, and Abbott; and has received research support from the Patient-Centered Outcomes Research Institute, NIH, U.S. Department of Defense, Agency for Healthcare Research and Quality, and Beckman Coulter. Dr Lindsell has received funding from AstraZeneca, bioMerieux, Entegrion, Endpoint Health, NIH, the U.S. Department of Defense, and the Centers for Disease Control and Prevention. Dr Stubblefield has received funding from the NIH/National Heart, Lung, and Blood Institute. Dr Lindenfeld has received research funding from AstraZeneca, Volumetrix, and NIH; and has received consulting fees from AstraZeneca, Abbott, Alleviant, Axon, Boston Scientific, CVRx, Edwards Lifesciences, Medtronic, Merck, Vascular Dynamics, VWave, and Whiteswell. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)