Dapagliflozin is the first SGLT2 inhibitor approved by the FDA for the treatment of patients with heart failure (NYHA class II-IV) with reduced ejection fraction.
Treatment with dapagliflozin (Farxiga; AstraZeneca) was found to improve symptom severity and health-related quality of life in heart failure (HF) patients with mildly reduced or preserved ejection fraction (EF) compared with placebo, according to findings from DELIVER phase 3 trials presented at the 2022 American Heart Association (AHA) Scientific Sessions and published in Journal of the American College of Cardiology.
Patients with HF and mildly reduced or preserved EF have an increased risk of death and hospitalizations, as well as a high burden of symptoms and physical limitations causing poor quality of life. Dapagliflozin is the first sodium-glucose cotransporter 2 (SGLT2) inhibitor approved by the FDA for the treatment of patients with heart failure (NYHA class II-IV) with reduced ejection fraction (HFrEF).
Previous research has shown the efficacy of dapagliflozin in preventing and delaying heart and kidney disease while protecting the organs, a key finding because of the fundamental connections between the heart, kidneys and pancreas.
Dapagliflozin is also approved for adults and children 10 years of age and older for the treatment of poorly controlled type 2 diabetes mellitus (T2D) as an adjunct to diet and exercise and for the treatment of chronic kidney disease based on DAPA-HF and DAPA-CKD findings phase 3 trials.
DELIVER is a double-blind, phase 3 study designed to evaluate the efficacy of dapagliflozin compared with placebo in the treatment of HF patients with or without T2D. Dapagliflozin is administered once daily in addition to the main therapy. Researchers used the Kansas City Cardiomyopathy Questionnaire (KCCQ) to analyze the effects of dapagliflozin, which was found to improve symptom severity, physical limitations and quality of life as measured by KCCQ scores and compared to placebo.
The primary endpoint was time to first occurrence of cardiovascular (CV) death, HF hospitalization, or HF emergency visit. Key secondary endpoints included the total number of HF events and cardiovascular death, time to cardiovascular death, and time to death from any cause. In addition, KCCQ total symptom score was a prespecified key secondary endpoint and physical limitations, clinical summary, and general summary were assessed at randomization, 1, 4, and 8 months.
Benefits were maintained up to 8 months with mean improvements in total symptom score of 2.4 points, physical limitations 1.9 points, clinical summary 2.3 points, and total summary 2.1 points greater than placebo. Fewer dapagliflozin-treated patients had a significant deterioration at month 8 compared to placebo, and more had at least small, moderate, or large improvements in health status in the assessed KCCQ domains.
“Many patients living with heart failure value their symptoms and physical function at least as much as avoiding death, making these results extremely clinically relevant. Given the fact that individuals with heart failure and a mildly reduced and preserved ejection fraction experience particularly poor health, the findings should prompt clinicians to seriously consider initiating SGLT2 inhibitors in this group, especially if patients are symptomatic,” said Mikhail Kosiborod, MD , cardiologist at St. Luke’s Mid-America Heart Institute, vice president for research at St. Luke’s Health System, professor of medicine at the University of Missouri-Kansas City, in a press release.
Farxiga improved symptom severity and health-related quality of life in patients with mildly reduced or preserved ejection fraction in the DELIVER phase III trial. AstraZeneca. November 7, 2022. Accessed November 8, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/farxiga-improved-symptom-burden-in-deliver-phase-iii-trial. html