Dapagliflozen May Decrease Fatal Risks of Heart Failure Associated With Higher Ejection Fraction

For patients suffering from a higher left ventricular ejection fraction, a sodium-glucose cotransporter 2 inhibitor could decrease risk of hospitalization or death from heart failure.

Dapagliflozen is suggested to reduce the risk of worsening heart failure and cardiovascular death in patients with heart failure and a mildly reduced or preserved ejection fraction. Currently, this risk is considered to increase for patients who have higher ejection fraction at greater than 40%.

Additionally, the researchers also did not notice a significant difference in the benefits of dapagliflozin among patients who had a greater, or less than, 60% ejection fraction.

“Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction,” wrote study authors in a report published in The New England Journal of Medicine.

Sodium-glucose cotransporter 2 (SLGT) inhibitors, once reserved for type 2 diabetes, have been found to treat chronic heart failure and a reduced ejection fraction at less than 40%. However, for moderate to higher ejection fraction, SLGTs are not proven to be an effective treatment.

The phase 3, international, multicenter, parallel-group, event-driven, double-blind, randomized, and controlled DELIVER trial assessed a 10 mg and once-daily dose of dapagliflozin (alongside usual therapy), against the placebo in 6263 patients with higher ejection fraction.

After a median of 2.3 years, 16.4% of patients dapagliflozin met the primary outcome—this was 19.5% in the placebo group. The factor of worsening heart failure occurred in 11.8% of dapagliflozin patients and 14.5% of placebo patients, and 7.4% of dapagliflozin patients died from cardiovascular issues, compared to 8.3% of those on the placebo.

“We observed no evidence of heterogeneity with respect to left ventricular ejection fraction in the DELIVER trial,” study authors said in the report. “This finding suggests that the benefit of SGLT2 inhibition is likely to extend throughout the full range of ejection fraction.”

During the trial, the primary outcome was worsening heart failure, which was characterized as either unplanned hospitalization or an urgent visit from heart failure, or cardiovascular death.

This outcome was consistent among subgroups, including those with or without type 2 diabetes mellitus, those with hospitalizations after 30 days, and those whose fraction was less than, but increased to, more than 40%.

Severe adverse events (AEs) impacted 43.5% of dapagliflozin patients, while 45.5% of patients in the placebo group were impacted by serious AEs. However, this drug was found to have a lower symptom burden than the placebo.

The trial used specific criteria to include and exclude certain participants, potentially generalizing findings. The results were limited by demographic, with only 5% of participants being Black; the burden of symptoms were determined only in patients who had been assessed before the COVID-19 pandemic in 2020.

“These data provide further evidence to support the use of an SGLT2 inhibitor as essential therapy in patients with heart failure, regardless of the presence or absence of type 2 diabetes mellitus or left ventricular ejection fraction,” the study authors wrote in the report.

Reference

Solomon, S.D., McMurray, J.J.V., Claggett, B. et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. The New England Journal of Medicine. September 22, 2022. Accessed September 26, 2022.