medwireNews: The addition of dapagliflozin to standard treatment may be beneficial for patients with established heart failure (HF) and reduced ejection fraction, indicate findings from the DAPA-HF trial.
Importantly, the study demonstrated an “entirely consistent benefit” of the sodium-glucose cotransporter (SGLT)2 inhibitor in patients both with and without diabetes, said John McMurray (University of Glasgow, UK), who presented the findings at the ESC Congress 2019 in Paris, France.
The global, event-driven phase III trial involved 4744 individuals with symptomatic HF and left ventricular ejection fraction of 40% or lower who were randomly assigned to receive once-daily treatment with dapagliflozin 10 mg or placebo in addition to standard drug and device therapy. A total of 45% of patients in each group had type 2 diabetes at baseline.
John McMurray talks about the results of the DAPA-HF trial, discussing whether the benefits of dapagliflozin for patients with heart failure could be extended to other SGLT2 inhibitors, and the next steps for research (3:29).
McMurray reported that the 2373 participants treated with dapagliflozin had a significant 26% reduced risk for the primary composite outcome of cardiovascular death, heart failure hospitalization, or an urgent heart failure hospital visit over a median follow-up of 18.2 months, compared with the 2371 individuals given placebo.
Cumulative rates of the primary composite outcome over a total of 2 years of follow-up were approximately 20% for the dapagliflozin group and 25% for the placebo arm.
This was “a highly statistically significant benefit,” and the number needed to treat with dapagliflozin to avoid one primary outcome event was 21, said McMurray.
He noted that when the two major components of the primary outcome were analyzed separately, dapagliflozin was associated with a significant 30% reduction in the risk for worsening HF events (unplanned HF hospitalization or urgent heart failure visit) and a significant 18% reduction in the risk for cardiovascular death relative to placebo.
In a “critically important” prespecified subgroup analysis, McMurray and co-investigators found a similar magnitude of benefit associated with dapagliflozin in patients with and without diabetes.
Specifically, among people with type 2 diabetes at baseline, 20% of the 1075 treated with dapagliflozin and 25% of the 1064 given placebo experienced a primary outcome event, and the corresponding rates among those without diabetes were 13% and 18%. These findings translated into a significant 25% risk reduction for people with diabetes and a significant 27% risk reduction for those without.
McMurray said that dapagliflozin was “very well tolerated” overall, with no difference between the two treatment groups in rates of volume depletion, renal adverse events, fracture, amputation, major hypoglycemia, and diabetic ketoacidosis.
Together, the DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) results suggest that “dapagliflozin offers a new approach to the treatment of patients with heart failure and reduced ejection fraction,” he concluded.
Commenting on these findings, discussant Marco Metra (University of Brescia, Italy) said that it remains to be determined whether dapagliflozin “will be effective in other phenotypes of heart failure,” such as HF with preserved ejection fraction (HFpEF), and whether other agents with similar mechanisms of action will have similar benefits.
“There are almost 20 ongoing trials with SGLT2 inhibitors including dapagliflozin, empagliflozin, and other drugs, and some of these trials are focused in patients with HFpEF,” he noted.
The DAPA-HF results were also presented at the 55th EASD Annual Meeting in Barcelona, Spain, and published simultaneously in The New England Journal of Medicine.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group