Background: Sodium–glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of incident heart failure hospitalization in individuals with type 2 diabetes who have, or are at high risk of, cardiovascular disease. Most patients in these trials did not have heart failure at baseline and the effect of SGLT2 inhibitors on outcomes in individuals with established heart failure (with or without diabetes) is unknown. Design and methods: The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF) is an international, multicentre, parallel group, randomized, double-blind, study in patients with chronic heart failure, evaluating the effect of dapagliflozin 10 mg, compared with placebo, given once daily, in addition to standard care, on the primary composite outcome of a worsening heart failure event (hospitalization or equivalent event, i.e. an urgent heart failure visit) or cardiovascular death. Patients with and without diabetes are eligible and must have a left ventricular ejection fraction ≤ 40%, a moderately elevated N-terminal pro B-type natriuretic peptide level, and an estimated glomerular filtration rate ≥ 30 mL/min/1.73 m 2 . The trial is event-driven, with a target of 844 primary outcomes. Secondary outcomes include the composite of total heart failure hospitalizations (including repeat episodes), and cardiovascular death and patient-reported outcomes. A total of 4744 patients have been randomized. Conclusions: DAPA-HF will determine the efficacy and safety of the SGLT2 inhibitor dapagliflozin, added to conventional therapy, in a broad spectrum of patients with heart failure and reduced ejection fraction.
Bibliographical noteFunding Information:
DAPA-HF is funded by AstraZeneca. Conflict of interest: J.J.V.McM. My employer, Glasgow University, has been paid by the following sponsors for the time spent as a committee member for a number of clinical trials (including travel and accommodation for some meetings related to these trials), advisory boards, other forms of consulting and lectures/presentations. These payments were made through a Consultancy with Glasgow University and no personal payments were received in relation to these trials/other activities. Abbvie, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Cardurion, DalCor, GSK, Imbria Pharmaceuticals, Kidney Research UK & Vifor-Fresenius Pharma, McMaster University, Merck, Novartis, Resverlogix and Theracos. D.L.DeM. is a consultant to the National Institutes of Health, the Food and Drug Administration and the pharmaceutical and medical device industry on the design, monitoring and analysis of clinical trials. He receives compensation for serving on several industry sponsored data and safety monitoring committees including AstraZeneca, Amgen, Actelion, Bristol-Myers Squibb, DalCor, GSK, Merck, Sanofi, Boehringer Ingelheim, Boston Scientific, Medtronic, Mesoblast, Intercept, Duke Clinical Research Institute and Population Health Research Institute of Hamilton. He holds no stock in any pharmaceutical or device company. S.E.I. has received professional fees and/or travel expense reimbursement from the following companies for services on steering/executive/publications committees for clinical research trials: Boehringer Ingelheim, AstraZeneca, Sanofi/Lexicon, Novo Nordisk, and Eisai (via the TIMI Group). He has also received honoraria for lectures and medical writing support (reported as transfer of value) from Boehringer Ingelheim. He has received consulting fees from VTV Therapeutics and Zafgen. L.K. has received payments to his institution from AstraZeneca and Novartis for participation in trial executive committees. He also received lecture fees from Novartis. M.N.K. has received research grant support from AstraZeneca, Boehringer Ingelheim, and has consulted for AstraZeneca, Boehringer Ingelheim, Amgen, GSK, Novo Nordisk, Sanofi, Merck, Eisai, Janssen, Glytec, Intarcia, Novartis, Bayer, Applied Therapeutics, Amarin. F.A.M. has received research grants from AstraZeneca, Novartis, Bristol-Myers Squibb, Vifor Pharma, and has consulted for Bristol-Myers Squibb, Astra Zeneca, Novar-tis, Baliarda, Janssen Cilag. P.P. reports personal fees and other from AstraZeneca, personal fees and other from Boehringer-Ingelheim, during the conduct of the study; grants, personal fees and other from Vifor Pharma, personal fees and other from Amgen, grants, personal fees and other from Servier, personal fees and other from Novartis, personal fees and other from Bayer, personal fees from Berlin-Chemie, personal fees from Pfizer, outside the submitted work. M.S.S. has received research grant support through Brigham and Women’s Hospital from Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Medicines Company, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Takeda (All >$10,000 per year), and has consulted for Amgen, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, Dyrnamix, IFM Therapeutics, Medicines Company, MedImmune, Merck (all
≤$10,000 per year except Amgen). S.D.S. has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, Novartis, Sanofi Pasteur, Theracos, and has consulted for Akros, Alnylam, Amgen, AstraZeneca, Bayer, BMS, Cardior, Corvia, Cytokinetics, Gilead, GSK, Ironwood, Merck, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Tenaya. A.M.L., O.B. and M.S. are employees of AstraZeneca.
- Clinical trial
- Heart failure
- Sodium–glucose co-transporter 2 inhibitor
- Type 2 diabetes mellitus
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
- Clinical Trial Protocol
- Multicenter Study
- Randomized Controlled Trial