Dapagliflozin in newly diagnosed versus worsening chronic HF: Insights from DAPA ACT HF-TIMI 68

ESC Heart Failure 2026 – In this prespecified analysis of DAPA ACT HF-TIMI 68, patients with newly diagnosed HF were younger, had fewer comorbidities, greater symptomatic improvement, better post-discharge outcomes, and fewer safety events than patients with worsening chronic HF. The efficacy and safety of in-hospital initiation of dapagliflozin were consistent regardless of HF chronicity.

This summary is based on the presentation of Paul Haller, MD, PhD (Vienna, Austria) at the ESC Heart Failure Congress 2026 - Dapagliflozin in patients hospitalized with newly diagnosed heart failure: a prespecified analysis of the DAPA ACT HF-TIMI 68 trial.

Introduction and methods

Clinical trials evaluating novel heart failure (HF) therapies have traditionally focused on ambulatory patients with chronic HF, with limited data available in patients with newly diagnosed HF.

The aim of this prespecified analysis of DAPA ACT HF-TIMI 68 was to: (1) compare the clinical profiles and outcomes of hospitalized HF patients according to HF chronicity; and (2) evaluate the treatment effects of in-hospital initiation of dapagliflozin according to HF chronicity.

DAPA ACT HF-TIMI 68 (Dapagliflozin Effect on Cardiovascular Events in Acute Heart Failure–Thrombolysis in Myocardial Infarction 68) was an investigator-initiated, randomized, double-blind, placebo-controlled trial of in-hospital initiation of dapagliflozin in 2401 patients hospitalized for HF. Patients were randomized within 1 to 14 days of admission to dapagliflozin 10 mg daily or placebo. Patients were followed for 2 months.

In this prespecified analysis, patients were stratified by HF chronicity into newly diagnosed HF (n=1074) or worsening chronic HF (n=1327).

The primary outcome was the first occurrence of cardiovascular death or worsening HF.

Main results

Newly diagnosed vs. worsening chronic HF

• Compared with patients with worsening chronic HF, those with newly diagnosed HF were younger, had fewer comorbidities, were less likely to have ischemic cause of HF, had lower NT-proBNP levels, and had higher eGFR.
• At 2 months, patients with newly diagnosed HF showed greater improvements in KCCQ-TSS than those with worsening chronic HF (difference: +11.4; 95%CI: 9.4-13.4; P<0.001).
• The cumulative incidence of the primary outcome was lower in patients with newly diagnosed HF compared with patients with worsening chronic HF.
• Safety outcomes occurred less frequently in patients with newly diagnosed HF compared with patients with worsening chronic HF.

Treatment effect of in-hospital initiation of dapagliflozin

• In the main trial, dapagliflozin did not significantly reduce the primary outcome compared with placebo, although the point estimate favored dapagliflozin (HR: 0.84; 95%CI: 0.66-1.07). In a meta-analysis of in-hospital initiation of SGLT2 inhibitors, the HR for the primary outcome was 0.71 (95%CI: 0.54-0.93).
• In this prespecified analysis, a similar pattern of efficacy of dapagliflozin was observed across the HF chronicity subgroups.
• Safety outcomes were similar between dapagliflozin and placebo regardless of HF chronicity (all P for interaction>0.05).

Conclusion

Patients with newly diagnosed HF were younger, had fewer comorbidities, greater symptomatic improvements, better post-discharge outcomes, and fewer overall safety concerns compared with patients with worsening chronic HF, irrespective of the randomized treatment. The efficacy and safety of in-hospital initiation of dapagliflozin were consistent regardless of HF chronicity.

 - Our reporting is based on the information provided at the ESC Heart Failure Congress 2026 -