Hot Line 2: DAPA ACT HF-TIMI 68
31 Aug 2025
Hot Line ESC Congress 2025 Dapagliflozin initiated in hospitalisation for heart failure: DAPA ACT HF-TIMI 68
“Initiating and optimising disease-modifying heart failure (HF) therapies during hospitalisation may improve outcomes; however, there are limited data on hospital initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2is),” explained Doctor David Berg (Brigham and Women's Hospital - Boston, USA). “We designed the double-blind, international DAPA ACT HF-TIMI 68 trial to test the hypothesis that in-hospital initiation of dapagliflozin, as compared with placebo, could improve outcomes among patients hospitalised for HF.”
Eligible patients were hospitalised with a primary diagnosis of HF, including signs and symptoms of fluid overload, with elevated natriuretic peptide levels. Patients were randomised to dapagliflozin 10 mg or placebo at least 24 hours and no later than 14 days after admission and as early as possible following stabilisation.
A total of 2,401 patients were randomised and the median time from hospital admission to randomisation was 3.6 days.
The primary outcome of CV death or worsening HF at 2 months occurred in 10.9% of patients with dapagliflozin and 12.7% with placebo (hazard ratio [HR] 0.86; 95% CI 0.68 to 1.08; p=0.20).
CV 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 with dapagliflozin and 4.5% with placebo (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 the EMPULSE trial with empagliflozin1 and the SOLOIST-WHF trial with sotagliflozin,2 assessing in-hospital initiation in 3,527 patients hospitalised for HF. SGLT2is reduced the early risk of CV 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).
Dr. Berg concluded: “In-hospital initiation of dapagliflozin did not significantly reduce the risk of CV death or worsening HF over the first 2 months in DAPA ACT HF-TIMI 68. However, the totality of the data suggests that in-hospital initiation of an SGLT2i reduces the early risk of CV death or worsening HF and all-cause mortality.”
References
- Voors AA, et al. Nat Med. 2022;28:568–574.
- Pitt B, et al. JACC Heart Fail. 2023;11:879–889.
