In-hospital initiation of dapagliflozin in patients hospitalized for acute heart failure (HF) did not significantly reduce the short-term risk of worsening HF or death, based on findings from the DAPA ACT HF-TIMI 68 trial presented at ESC Congress 2025.

The trial, which was conducted at 210 sites in the U.S., Canada, Poland, Hungary and the Czech Republic, randomized 2,401 patients (median age 69 years/34% women) to 10 mg daily of dapagliflozin or placebo as early as possible following stabilization – at least 24 hours and no later than 14 days after hospital admission. All patients were hospitalized with a primary diagnosis of HF, including signs and symptoms of fluid overload, and were required to have elevated natriuretic peptide levels during the index hospitalization.

The primary outcome of cardiovascular death or worsening HF over the first two months occurred in 11% of patients in the dapagliflozin group compared with 13% of patients in the placebo group. Cardiovascular death was also lower in the dapagliflozin group (2.5% vs. 3.1%, respectively), as was the number of worsening HF events (9.4% vs. 10.3%, respectively). In other findings, all-cause mortality occurred in 3% of patients in the dapagliflozin group and 4.5% of patients in the placebo group. However, rates of symptomatic hypotension and rates of worsening kidney function were higher among those receiving dapagliflozin vs. placebo (3.6% vs. 2.2% and 5.9% vs. 4.7%, respectively).

Researchers also conducted a prespecified meta-analysis of DAPA ACT HF-TIMI 68 and two other trials assessing in-hospital initiation of SGLT2is (empagliflozin and sotagliflozin) in 3,527 patients hospitalized for HF. These findings found 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).

"In-hospital initiation of dapagliflozin did not significantly reduce the risk of cardiovascular death or worsening HF over the first two months in DAPA ACT HF-TIMI 68," said Principal Investigator David Berg, MD, FACC. "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."