Study title: DAPA ACT HF-TIMI 68: Dapagliflozin in Patients Hospitalized for Acute Heart Failure

Conferance: ESC Congress 2025, Madrid

Link: https://esc365.escardio.org/presentation/312142

Prepared by: Dr. Yunus Emre Özbebek

Introduction
SGLT2 inhibitors reduce the risk of cardiovascular (CV) death or worsening heart failure (HF) in patients with chronic HF; however, evidence regarding initiation during hospitalization is limited. DAPA ACT HF–TIMI 68 was designed to evaluate the efficacy and safety of initiating dapagliflozin (10 mg/day) in patients hospitalized with acute HF. The primary hypothesis was that in-hospital initiation of dapagliflozin would reduce the risk of CV death or worsening HF during the early post-discharge period.

Methods
This was an international, multicenter, phase 3, double-blind, placebo-controlled, 1:1 randomized trial. A total of 2,401 patients were enrolled, irrespective of left ventricular ejection fraction (HFrEF/HFpEF), and included both de novo and worsening chronic HF, with or without type 2 diabetes. Randomization occurred at least 24 hours and up to 14 days after hospital admission, once hemodynamic stabilization was achieved. Follow-up duration was 2 months. The primary endpoint was defined as CV death or worsening HF (advanced decompensation requiring intensive support during the index hospitalization, post-discharge HF rehospitalization, or urgent/ambulatory HF visit requiring IV diuretics).

Results
The primary endpoint was not significantly reduced (HR 0.86; 95% CI 0.68–1.08; p=0.20). In component analyses, CV death had an HR of 0.78 (95% CI 0.48–1.27), and worsening HF had an HR of 0.91 (95% CI 0.71–1.18). For other outcomes, the HR for CV death or HF rehospitalization was 0.79 (95% CI 0.62–1.02), and for all-cause mortality it was 0.66 (95% CI 0.43–1.00). Subgroup analyses showed consistent effects across de novo vs. chronic HF, LVEF ≤/>40%, eGFR < / ≥60 mL/min/1.73 m², and NT-proBNP/BNP below or above the median, with no significant interactions.

Safety
Dapagliflozin was safe and well tolerated. Symptomatic hypotension occurred in 3.6% vs. 2.2%, worsening kidney function in 5.9% vs. 4.7%, major hypoglycemia in 0.2% vs. 0.3%, and diabetic ketoacidosis in 0% vs. 0% for dapagliflozin vs. placebo, respectively. The rate of drug discontinuation due to adverse events was 4.8% vs. 4.7%.

Conclusion
At two months of follow-up, in-hospital initiation of dapagliflozin did not significantly reduce the primary composite endpoint. However, pooled evidence from randomized trials suggests that starting an SGLT2 inhibitor in hospitalized patients may lower the risk of CV death or worsening HF and all-cause mortality in the early post-discharge period. The safety profile was consistent with the known class effects of SGLT2 inhibitors, supporting their use in the inpatient setting. Meta-analysis results demonstrated additional benefit, with HR 0.71 for CV death or worsening HF and HR 0.57 for all-cause mortality compared with placebo.