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Trial explainer

DAPA-HF: what the trial showed

In 4,744 patients with symptomatic heart failure and an ejection fraction of 40% or less, dapagliflozin 10 mg daily on top of recommended therapy reduced worsening heart failure or cardiovascular death from 21.2% to 16.3% over a median of 18.2 months, with and without diabetes.

Main cited publication: Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. New England Journal of Medicine, 2019. PMID 31535829. Results are summarized from the cited trial report and any companion publications listed below.

At a glance

DesignPhase 3, randomised, double-blind, placebo-controlled, event-driven
Population4,744 adults with NYHA class II to IV heart failure and a left ventricular ejection fraction of 40% or less, with or without type 2 diabetes, on recommended heart failure therapy
InterventionDapagliflozin 10 mg once daily
ComparatorPlacebo
Follow-upMedian 18.2 months
RegistrationNCT03036124
FundingAstraZeneca

Primary outcome

Composite of worsening heart failure (hospitalisation or urgent visit needing intravenous therapy) or cardiovascular death.

Dapagliflozin 10 mg once dailyPlaceboEffect
16.3% (386 of 2,373)21.2% (502 of 2,371)Hazard ratio 0.74 (95% CI 0.65 to 0.85), P<0.001

Key findings

  • A first worsening heart failure event occurred in 10.0% with dapagliflozin and 13.7% with placebo (HR 0.70, 95% CI 0.59 to 0.83).
  • Cardiovascular death occurred in 9.6% versus 11.5% (HR 0.82, 95% CI 0.69 to 0.98), and all-cause death in 11.6% versus 13.9% (HR 0.83, 95% CI 0.71 to 0.97).
  • The effect was similar in patients with and without type 2 diabetes, which established SGLT2 inhibition as a heart failure treatment rather than a glucose-lowering strategy.
  • The absolute reduction in the primary outcome was about 4.9 percentage points over the trial period, roughly one event prevented for every 21 patients treated for 18 months.

Harms and safety

  • Adverse events related to volume depletion, renal dysfunction, and hypoglycaemia did not differ between groups.
  • The abstract does not report an excess of serious adverse events with dapagliflozin.

Limitations

  • Median follow-up was 18 months, so longer-term effects and rare harms are not captured by the primary publication.
  • Patients were already on recommended therapy in a trial setting; real-world populations are older, with more comorbidity and lower adherence.
  • Industry funded and placebo controlled; there is no head-to-head comparison with other SGLT2 inhibitors.

Where it sits in guidelines

The 2021 ESC heart failure guideline gives dapagliflozin and empagliflozin a class I recommendation in symptomatic HFrEF, as one of the four pillars of therapy alongside an ACE inhibitor or ARNI, a beta-blocker, and an MRA, largely on the strength of DAPA-HF and EMPEROR-Reduced.

CliniAtlas answers that use this trial

Written for healthcare professionals as an orientation to the primary publication, not as a substitute for reading it. For literature search, education, and professional evidence review only. Not for diagnosis, treatment selection, triage, monitoring, prognosis, or patient-specific clinical decision-making.