DIABETES & HF
DAPA-HF: dapagliflozin and prevention of adverse-outcomes in heart failure
Mikhail Kosiborod, MD
Division of Cardiology, Saint Luke’s Mid America Heart Institute, Kansas City, MO, USA
Department of Medicine, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA
The George Institute for Global Health, Sydney, Australia
Silvio Inzucchi, MD
Section of Endocrinology, Yale School of Medicine, New Haven, CT, USA
In patients with heart failure (HF) and reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was significantly lower with dapagliflozin than with placebo.
Of interest, the reduced risk was present regardless of the presence or absence of diabetes.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the risk of a first hospitalisation for HF. However, sufficient data is still lacking regarding the effects of SGLT2 inhibitors in patients with established HF and reduced ejection fraction, regardless of the presence or absence of type 2 diabetes.
DAPA-HF investigated the effects of dapagliflozin in patients with HF and reduced ejection fraction with or without diabetes.
Type of study, patients, and inclusion criteria
Randomised, phase 3, placebo-controlled trial.
New York Heart Association (NHYA) class II, III, or IV HF and an ejection fraction ≤40%.
Total patients randomised: 4744.
Dapagliflozin 10 g/day (n = 2373).
Placebo (n = 2371).
Primary outcome measure
Composite of worsening HF (hospitalisation or an urgent visit resulting in intravenous therapy for HF) or cardiovascular death.
Over a median follow-up of 18.2 months, the primary outcome occurred in 16.3% of patients in the dapagliflozin group vs. 21.2% with placebo (HR, 0.74; 95% CI 0.65-0.85; P <0.001).
A first worsening HF event occurred in 10% of patients in the dapagliflozin group compared to 13.7% with placebo (HR, 0.70; 95% CI 0.59-0.83).
Death from cardiovascular causes occurred in 9.6% of patients treated with dapagliflozin compared to 11.5% in the placebo group (HR, 0.82; 95% CI 0.69-0.98).
Of note, findings in patients with diabetes were similar to those in patients without diabetes.
The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycaemia did not differ between treatment groups.
Among patients with HF and reduced ejection fraction, the risk of worsening HF or death from cardiovascular causes was lower among those who received dapagliflozin than placebo.
The reduced risk was present regardless of the presence or absence of diabetes.
Key Messages/Clinical Perspectives
These encouraging results substantially reinforce observations from previous clinical trials with dapagliflozin.
It remains to be seen if SGLT2 inhibitors should be used in eligible patients with HF and reduced ejection fraction, independently of the presence of comorbid diabetes.
Presenter disclosure: The presenters has reported the follow relationships: M. Kosiborod: AstraZeneca, Boehringer Ingelheim, Amarin, Applied Therapeutics, Amgen, Bayer, Eisai, Glytec, GSK, Eli Lilly, Merck (Diabetes), Novartis, Novo Nordisk, Sanofi. S. Inzucchi: AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Sanofi/Lexicon, Merck, VTV Therapeutics.
Medical writer: Patrick Moore, PhD
Reviewer: Marco Gallo, MD
Local reviewers: Marco Gallo, MD (Italia); Anna Novials Sardá, MD, PhD (España); Eric Renard, MD, PhD (France); Peter Schwarz, MD, PhD (Deutschland)
Scientific Editor: Florian Toti, MD