Revolutionary Trial Unveils Surprising Results

In a groundbreaking study presented at the European Society of Cardiology Congress 2025 in Madrid, researchers revealed that dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, failed to significantly lower the short-term risk of cardiovascular death or worsening heart failure (HF) in patients admitted for the condition. This finding emerges from the extensive DAPA ACT HF-TIMI 68 trial.

Heart Failure Epidemic on the Rise

Heart failure has become a leading cause of hospitalization globally, with cases soaring in the last decade. Patients facing this life-threatening condition often encounter heightened risks during the early post-discharge period. Past studies have indicated that early initiation of heart failure therapies, such as beta-blockers and mineralocorticoid receptor antagonists, can significantly enhance patient outcomes.

Trial Insights: A Closer Look at DAPA ACT

Doctor David Berg, a lead investigator at Brigham and Women’s Hospital, explained that limited research exists on the effective use of sodium-glucose cotransporter-2 inhibitors in hospitalized HF patients. The DAPA ACT trial was meticulously designed to evaluate whether starting dapagliflozin in the hospital could effectively lower the immediate risk of cardiovascular issues for these patients.

Study Design and Participants

Conducted across 210 sites in the USA, Canada, Poland, Hungary, and the Czech Republic, the double-blind, placebo-controlled trial enrolled 2,401 participants, aged 18 and above, who were hospitalized with confirmed HF. Patients were randomly assigned to receive either dapagliflozin 10 mg daily or a placebo, initiating treatment 24 hours to 14 days after hospital admission.

Disappointing Outcomes

The trial's primary efficacy outcome—comprised of cardiovascular death or worsening HF within the first two months—showed that 10.9% of patients on dapagliflozin experienced poor outcomes, compared to 12.7% in the placebo group. Notably, cardiovascular death rates were 2.5% for dapagliflozin versus 3.1% for the placebo.

Insights from Meta-Analysis

Despite the disappointing results of the DAPA ACT trial, a pre-specified meta-analysis including two other SGLT2 trials—empagliflozin and sotagliflozin—suggested a silver lining. This larger analysis of 3,527 patients demonstrated that in-hospital initiation of SGLT2 inhibitors could indeed reduce early risks of cardiovascular death and all-cause mortality.

Looking Ahead: Implications of the Findings

While DAPA ACT did not achieve its primary endpoints, the overall data indicates that starting SGLT2 inhibitors in the hospital may offer significant benefits to heart failure patients. Berg stated, 'Although in-hospital initiation of dapagliflozin did not significantly reduce the risk of cardiovascular death or worsening HF, the totality of trial data suggests there may still be a profound benefit to initiating treatment early.' The search for more effective solutions continues in the fight against heart failure.