Madrid, Spain – 30 August 2025: In-hospital initiation of dapagliflozin did not significantly reduce the short-term risk of cardiovascular death or worsening heart failure (HF) in patients admitted for HF, although positive effects were seen when combining trial data, according to late-breaking research presented in a Hot Line session today at ESC Congress 2025.1
Hospitalisation for HF is the leading cardiovascular reason for hospital admission2 and is associated with a high risk of death and other adverse outcomes during admission and in the weeks after discharge.3 “Initiating and optimising disease-modifying HF therapies during hospitalisation may improve both short- and long-term outcomes; however, there are limited data on initiating sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients hospitalised for HF,” explained Doctor David Berg, an Investigator in the TIMI Study Group at Brigham and Women's Hospital, Boston, USA, and Principal Investigator of the DAPA ACT HF-TIMI 68 trial. “We designed the trial to test the hypothesis that in-hospital initiation of the SGLT2i, dapagliflozin, as compared with placebo, could safely and effectively decrease the early risk of cardiovascular death or worsening HF among patients hospitalised for HF.”
The DAPA ACT HF-TIMI 68 trial was a double-blind, placebo-controlled randomised trial conducted at 210 sites in USA, Canada, Poland, Hungary and the Czech Republic. Eligible patients were ≥18 years of age and were currently hospitalised with a primary diagnosis of HF, including signs and symptoms of fluid overload. Patients were required to have elevated natriuretic peptide levels during the index hospitalisation. Patients were randomised 1:1 to dapagliflozin 10 mg daily or placebo at least 24 hours and no later than 14 days after hospital admission and as early as possible following initial stabilisation. The primary efficacy outcome was a composite of cardiovascular death or worsening HF over the first 2 months.
A total of 2,401 patients were randomised. The median age was 69 years and 33.9% were women. The median time from hospital admission to randomisation was 3.6 days.
The primary outcome of cardiovascular death or worsening HF occurred in 10.9% of patients in the dapagliflozin group and 12.7% of patients in the placebo group (hazard ratio [HR] 0.86; 95% confidence interval [CI] 0.68 to 1.08; p=0.20).
Cardiovascular death occurred in 2.5% of patients with dapagliflozin and 3.1% with placebo (HR 0.78; 95% CI 0.48 to 1.27), while a worsening HF event occurred in 9.4% and 10.3% of patients, respectively (HR 0.91; 95% CI 0.71 to 1.18).
All-cause mortality occurred in 3.0% of patients in the dapagliflozin group and 4.5% of patients in the placebo group (HR 0.66; 95% CI 0.43 to 1.00). Rates of symptomatic hypotension were 3.6% and 2.2%, respectively, and rates of worsening kidney function were 5.9% and 4.7% with dapagliflozin and placebo, respectively.
A prespecified meta-analysis was conducted of DAPA ACT HF-TIMI 68 plus trials with two other SGLT2is (empagliflozin and sotagliflozin) assessing in-hospital initiation in 3,527 patients hospitalised for HF.4,5 SGLT2is reduced the early risk of cardiovascular death or worsening HF (HR 0.71; 95% CI 0.54 to 0.93; p=0.012) and all-cause mortality (HR 0.57; 95% CI 0.41 to 0.80; p=0.001).
Doctor Berg concluded: “In-hospital initiation of dapagliflozin did not significantly reduce the risk of cardiovascular death or worsening HF over the first 2 months in DAPA ACT HF-TIMI 68. However, the totality of trial data suggests that in-hospital initiation of an SGLT2i reduces the early risk of cardiovascular death or worsening HF and all-cause mortality.”
ENDS
Notes to editor
This press release accompanies both a presentation and an ESC press conference at ESC Congress 2025.
It does not necessarily reflect the opinion of the European Society of Cardiology.
Funding: The study was funded by AstraZeneca.
Disclosures: Doctor Berg has received institutional research grant support through Brigham and Women’s Hospital from AstraZeneca, Merck and Pfizer; received consulting fees from AstraZeneca, Pfizer, Mobility Bio and Youngene Therapeutics; 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.
References and notes:
1‘DAPA ACT HF-TIMI 68: Dapagliflozin in patients hospitalised for acute heart failure’ presented during HOT LINE 2 on 30 August 2025 at 08:15 to 08:25 in Madrid (Main Auditorium).
2Martin SS, Aday AW, Allen NB, et al. 2025 Heart disease and stroke statistics: A report of US and global data from the American Heart Association. Circulation. 2025;151:e41–e660.
3Bozkurt B, Ahmad T, Alexander K, et al. HF STATS 2024: Heart failure epidemiology and outcomes statistics. An updated 2024 report from the Heart Failure Society of America. J Card Fail. 2025;31:66–116.
4Voors AA, Angermann CE, Teerlink JR, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. 2022;28:568–574.
5Pitt B, Bhatt DL, Szarek M, et al. Effect of sotagliflozin on early mortality and heart failure-related events: A post hoc analysis of SOLOIST-WHF. JACC Heart Fail. 2023;11:879–889.
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