David Berg, MD, is a cardiologist and critical care specialist at Brigham and Women’s Hospital and a member of the TIMI Study Group.

David Berg, MD

In a new meta-analysis examining the DAPA-HF, DELIVER, and DAPA-ACT-HF trials, dapagliflozin substantially reduced the risk of cardiovascular death or worsening 

DAPA-TRIO-HF: Dapagliflozin Improves HF Outcomes Regardless of Healthcare Setting

The DAPAgliflozin for TReatment of Inpatients and Outpatients with Heart Failure (DAPA-TRIO-HF) meta-analysis included the DAPA-HF, DELIVER, and DAPA-ACT-HF-TIMI 68 trials of dapagliflozin in HF. These prior studies had displayed substantial improvements in cardiovascular death risk, as well as worsening HF and all-cause mortality; however, they largely prioritized either hospitalized or ambulatory patients. To address this, investigators initiated the present analysis to examine dapagliflozin in both groups.

“Almost a year ago, I presented the primary results of the DAPA ACT HF-TIMI 68 trial, and that new data really gave us an opportunity to question the effect of dapagliflozin not only across the spectrum of ejection fraction, but across the different heart failure care settings – both inpatients and outpatients,” David Berg, MD, a cardiologist and critical care specialist at Brigham and Women’s Hospital and a member of the TIMI Study Group, told 

 in an exclusive interview. “It allowed us to ask questions about whether we want to view heart failure patients holistically.”

All patients enrolled in DAPA-HF and 98.6% of patients in DELIVER were randomized in the ambulatory setting, while all patients in the DAPA ACT HF-TIMI 68 trial were enrolled during hospitalization for HF. Median follow-up was 18 months in DAPA-HF, 28 months in DELIVER, and 2 months in DAPA ACT HF-TIMI 68. The analysis’s primary endpoint was a composite of cardiovascular death or worsening HF. Secondary endpoints included each component individually, cardiovascular death or hospitalization for HF, and all-cause mortality.

The 3 trials included a total of 13,408 patients, with a mean age of 69 years. 43% of patients had diabetes mellitus, and 54% were hospitalized for HF. Regarding left ventricular ejection fraction, 48% of patients had ≤40%, 17% had 41-49%, and 35% had ≥50%. All 3 trials randomly assigned participants to either dapagliflozin or placebo.

Across the 3 trials, dapagliflozin recipients saw a reduction of 22% in cardiovascular death or worsening HF (HR, 0.78; 95% CI, 0.71-0.86; 

 <.001). Cardiovascular death on its own was reduced by 15% (HR, 0.85; 95% CI, 0.75-0.96; 

 = .011), while worsening HF was reduced by 22% (HR, 0.78; 95% CI, 0.69-0.87; 

 <.001). The composite secondary endpoint of cardiovascular death or hospitalization for HF was reduced by 23% (HR, 0.77; 95% CI, 0.7-0.84; 

 <.001), while all-cause mortality saw a reduction of 13% (HR, 0.87; 95% CI, 0.76-0.99; 

 = .034). Berg and colleagues also found no heterogeneity in the treatment effects of dapagliflozin in any subgroup, including ambulatory versus hospitalized treatment.

Ultimately, Berg and colleagues concluded that dapagliflozin’s treatment results are consistent regardless of the care setting in which treatment is initiated. Additionally, treatment effects were seen regardless of age, sex, race, diabetes status, baseline LVEF, background medication use, or eGFR. The team concluded that these data support the early initiation and usage of dapagliflozin across the HF care continuum.

“We now have very robust data for dapagliflozin across the ejection fraction spectrum and across different care settings,” Berg said. “What I hope to see from here is greater adoption of this therapy, and implementation of this therapy in clinical practice, both for hospitalized and ambulatory patients.”

Editors’ Note: Berg reports disclosures with AstraZeneca, CeleCor Therapeutics, Merck, Novo Nordisk, Pfizzer, Radcliffe Cardiology, and others.

Berg D. DAPAgliflozin for TReatment of Inpatients and Outpatients with Heart Failure: The DAPA-TRIO-HF Meta-Analysis. Presented at the Heart Failure Society of America Annual Scientific Meeting. September 29, 2025. Accessed September 22, 2026.

Berg DD, Vaduganathan M, Docherty KF, Bellavia A, Murphy SA, Claggett BL, Desai AS, Inzucchi SE, Patel SM, Wiviott SD, Solomon SD, McMurray JJV, Sabatine MS. Dapagliflozin in Patients With Heart Failure Across the Care Spectrum: A Meta-Analysis of DAPA-HF, DELIVER, and DAPA ACT HF-TIMI 68. JACC Heart Fail. 2026 Aug;14(8):103232. 

Videos

David Berg, MD, discusses his meta-analysis of 3 major trials of dapagliflozin, which determined its efficacy in reducing cardiovascular death risk.

David Berg, MD

Articles