Rationale and Design of the Dapagliflozin Effect on Cardiovascular Events in Acute Heart Failure (DAPA ACT HF)-TIMI 68 Trial
- PMID: 40335233
- DOI: 10.1016/j.jchf.2025.03.014
Rationale and Design of the Dapagliflozin Effect on Cardiovascular Events in Acute Heart Failure (DAPA ACT HF)-TIMI 68 Trial
Abstract
Although sodium-glucose cotransporter 2 inhibitors reduce the risk of cardiovascular death or worsening heart failure (HF) in patients with chronic HF, there are limited data on initiation in hospitalized patients with HF. DAPA ACT HF-TIMI 68 (Dapagliflozin and Effect on Cardiovascular Events in Acute Heart Failure - Thrombolysis in Myocardial Infarction 68) is an international, randomized, double-blind trial evaluating the initiation of dapagliflozin (10 mg daily) vs placebo in 2,401 patients hospitalized for acute HF. Patients were enrolled irrespective of left ventricular ejection fraction, type 2 diabetes status, or chronicity of HF (de novo and worsening chronic HF). Randomized participants receive blinded treatment for 2 months. The primary efficacy endpoint is time to first occurrence of cardiovascular death or worsening HF (worsening HF during the index admission, rehospitalization for worsening HF, or urgent HF visit). Key safety endpoints include symptomatic hypotension and worsening kidney function. This is the first cardiovascular outcomes trial designed specifically to evaluate the efficacy and safety of in-hospital initiation of dapagliflozin in patients hospitalized for the management of acute HF. (Dapagliflozin and Effect on Cardiovascular Events in Acute Heart Failure - Thrombolysis in Myocardial Infarction 68 [DAPA ACT HF-TIMI 68]; NCT04363697; EudraCT # 2022-001262-35).
Keywords: clinical trial; hospitalization; sodium-glucose cotransporter 2 inhibitors; worsening heart failure.
Copyright © 2025. Published by Elsevier Inc.
Conflict of interest statement
Funding Support and Author Disclosures The DAPA ACT HF-TIMI 68 trial was funded by AstraZeneca. Drs Berg, Patel, Haller, Sabatine, and Wiviott, Ms Cange, and Ms Murphy are members of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Ionis Pharmaceuticals, Janssen Research and Development, MedImmune, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Roche, Saghmos Therapeutics, Siemens Healthcare Diagnostics, Softcell Medical Limited, The Medicines Company, Verve Therapeutics, and Zora Biosciences. Dr Berg has received consulting fees from AstraZeneca, Pfizer, Mobility Bio, and Youngene Therapeutics; has received honoraria from the Medical Education Speakers Network, Metabolic Endocrine Education Foundation, Pri-Med, and USV Private Limited; and has served on clinical endpoint committees for studies sponsored by Beckman Coulter, CeleCor Therapeutics, Kowa Pharmaceuticals, Novo Nordisk, and Tosoh Biosciences. Dr Patel has received consulting fees from Janssen. Dr Haller has received travel grants from the German Center of Cardiovascular Research (DZHK); has received funding by the German Foundation for Heart Research; and is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation; 10086/1-1). Dr Bělohlávek has received lecture honoraria from Novartis, AstraZeneca, Boehringer Ingelheim, Getinge, Abiomed, and Resuscitec. Dr Desai has received institutional research grants from Abbott, Alnylam Pharmaceuticals, AstraZeneca, Bayer, Novartis, and Pfizer; and personal consulting fees from Abbott, Alnylam Pharmaceuticals, AstraZeneca, Bayer, Biofourmis, Boston Scientific, Endotronix, GlaxoSmithKline, iRhythm Technologies, Medpace, Medtronic, Merck, Novartis, Parexel, Porter Health, Regeneron, River 2 Renal, Roche, Veristat, Verily, and Zydus. Dr Drożdż has received research grants from AstraZeneca and Servier Poland; and lecture fees from Bayer Healthcare, Boehringer Ingelheim, and Novartis. Dr Inzucchi has received honoraria for consulting and/or clinical trial committee work from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Merck, Pfizer, and Bayer; and has given lectures sponsored by AstraZeneca and Boehringer Ingelheim. Dr McMurray has received payments to Glasgow University for clinical trials and other research projects from the British Heart Foundation, National Institutes of Health–National Heart, Lung, and Blood Institute, Alnylam Pharmaceuticals, AstraZeneca, Bayer, Cardurion, Cytokinetics, Novartis, and Roche; personal consultancy fees from Alnylam Pharmaceuticals, AnaCardio, AstraZeneca, Bayer, Cardurion, Cytokinetics, Novartis, River BioMedics, Biohaven Pharmaceuticals, Chugai Pharmaceuticals, Protherics Medicine Developments, and DalCor Pharmaceuticals; and personal lecture fees from Alkem Metabolics, AstraZeneca, Canadian Medical and Surgical Knowledge Translation Research Group, Centrix Healthcare, Emcure Pharmaceuticals, Eris Lifesciences, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J.B. Chemicals and Pharmaceuticals, Lupin Pharmaceuticals, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, Translational Medicine Academy, Regeneron, MCI India, Hilton Pharmaceuticals, IMEDIC Pharmaceuticals Micro Labs, At the Limits, ARMGO Pharmaceuticals; he serves on the Data Safety Monitoring Board of WCG Clinical Services; and he is a director at Global Clinical Trial Partners (which provides clinical trial services such as endpoint committees and educational programs). Dr Merkely has received lecture fees from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, CSL Behring, Daiichi Sankyo, Medtronic, and Novartis. Dr O’Meara holds the Montreal Heart Institute’s Carolyn and Richard J. Renaud Chair for Research in Heart Failure, with fees paid through her institution for this chair and for the following: Canadian Heart Function Alliance team grant, funded by the Canadian Institutes of Health Research (steering committee member), and involvement in the following trials as a steering committee member for DAPA ACT HF-TIMI 68 (TIMI Study Group and AstraZeneca), GARDEN-TIMI 74 (TIMI Study Group and Pfizer), HEART-FID (American Regent), CARDINAL-HF (Cardurion), HERMES (National Lead Investigator, Novo Nordisk), and BalancedD-HF (NLI, AstraZeneca); has received consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer, Novartis, and Novo Nordisk; and has received speaker fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Novo Nordisk, and Pfizer. Dr Verma has received research grants and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, Pfizer, PhaseBio, S & L Solutions Event Management, and Sanofi. Dr Sabatine has received research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Ionis, Marea, Merck, Novartis, Pfizer, Saghmos Therapeutics, and Verve Therapeutics; and has been a consultant for Amgen, AMPEL BioSolutions, Anthos Therapeutics, AstraZeneca, Beren Therapeutics, Boehringer Ingelheim, Dr Reddy’s Laboratories, Fibrogen, Merck, Moderna, Novo Nordisk, Precision BioSciences, and Silence Therapeutics. Dr Wiviott has received research grants from Amgen, AstraZeneca, Janssen, Merck, and Pfizer; has received consulting fees from Icon, Novo Nordisk, and Verian; and has received speaking honoraria from Harvard Medical School.
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