In-hospital start of dapagliflozin shows no significant short-term benefit in heart failure patients

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.

Hospitalization for HF is the leading cardiovascular reason for hospital admission and is associated with a high risk of death and other adverse outcomes during admission and in the weeks after discharge.

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 hospitalized for HF. 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 hospitalized for HF."

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

The DAPA ACT HF-TIMI 68 trial was a double-blind, placebo-controlled randomized 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 randomized. The median age was 69 years and 33.9% were women. The median time from hospital admission to randomization 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 hospitalized 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."