In-hospital initiation of dapagliflozin did not significantly lower the short-term risk of cardiovascular death or worsening heart failure (HF) in patients admitted for HF, according to late-breaking results from the DAPA ACT HF-TIMI 68 trial presented at ESC Congress 2025. However, a pooled analysis of trial data with other sodium-glucose cotransporter-2 inhibitors (SGLT2is) showed early clinical benefits.
Heart failure remains the leading cardiovascular cause of hospitalisation and is associated with a high risk of death and adverse outcomes both during admission and shortly after discharge. Initiating and optimising disease-modifying therapies during hospitalisation may improve outcomes, yet there are limited data on starting SGLT2is in this setting.
The DAPA ACT HF-TIMI 68 was designed to test whether in-hospital initiation of dapagliflozin, compared with placebo, could safely and effectively reduce the early risk of cardiovascular death or worsening HF.
The trial was conducted at 210 sites across the USA, Canada, Poland, Hungary, and the Czech Republic. Eligible patients were ≥18 years of age, hospitalised with a primary diagnosis of HF and clinical evidence of fluid overload, and required to have elevated natriuretic peptide levels. Patients were randomised 1:1 to dapagliflozin 10 mg daily or placebo between 24 hours and 14 days after admission, as soon as clinically stabilised.
A total of 2,401 patients were randomised. Median age was 69 years, 33.9% were women, and the median time from hospital admission to randomisation was 3.6 days.
The primary endpoint (a composite of cardiovascular death or worsening HF within 2 months) occurred in 10.9% of patients receiving dapagliflozin and 12.7% of those receiving placebo. Cardiovascular death occurred in 2.5% of the dapagliflozin group versus 3.1% with placebo. Worsening HF was reported in 9.4% and 10.3%, respectively. All-cause mortality was 3.0% with dapagliflozin versus 4.5% with placebo.
Safety findings included rates of symptomatic hypotension (3.6% vs. 2.2%) and worsening kidney function (5.9% vs. 4.7%) for dapagliflozin and placebo, respectively.
A prespecified meta-analysis combined DAPA ACT HF-TIMI 68 with two other trials evaluating in-hospital initiation of SGLT2is (empagliflozin and sotagliflozin) in 3,527 patients. Results showed significant reductions in cardiovascular death or worsening HF and in all-cause mortality.
Overall, these findings show that in-hospital initiation of dapagliflozin did not significantly reduce cardiovascular death or worsening HF over the first 2 months in DAPA ACT HF-TIMI 68. But the totality of evidence indicates that early in-hospital initiation of an SGLT2i can reduce the short-term risk of cardiovascular death, worsening HF, and all-cause mortality.
Source: ESC
Image Credit: ESC
