Pre-specified pooled analysis from phase 3 trials demonstrates 14% reduction in CV mortality and from any cause by 10% in individuals with HF, irrespective of ejection fraction.
Dapagliflozin (Farxiga; AstraZeneca) demonstrated mortality benefit compared with the placebo, in individuals with heart failure (HF), in new results from a pooled analysis from the phase 3 DAPA-HF (NCT03057977) and DELIVER (NCT03619213) trials.
The findings, which were published in Nature Medicine, were presented at the European Society of Cardiology Congress 2022.
“Heart failure remains one of the leading causes of death worldwide with high unmet need for some 64 million [individuals]. This analysis demonstrates [dapagliflozin]’s ability to treat patients across the full left ventricular ejection fraction spectrum and reduce the risk of cardiovascular death,” Mene Pangalos, executive vice president of BioPharmaceuticals R&D at AstraZeneca said in a statement.
The reduction in risk of cardiovascular (CV) death was consistent across the pre-specified subgroups, according to the results of the study.
It is the first analysis to demonstrate a mortality benefit with a HF medication for those with HF across the left ventricular ejection fraction (LVEF) range.
Investigators found that dapagliflozin reduced the risk of CV death by 14% over the median follow up of 22 months in those with HF irrespective of LVEF. Additionally, they found that death by any cause was reduced by 10%, and total, including first and repeat, hospitalization for HF was reduced by 29%.
Furthermore, the composite of death from CV causes, myocardial infarction, or stroke was reduced by 10% in those with HF, irrespective of LVEF.
“In this patient-level meta-analysis including over 11,000 patients with [HF] across the full range of ejection fraction, dapagliflozin reduced the risk of both [CV] death and [HF] hospitalization. These results underpin the valuable role dapagliflozin can play in clinical practice, as we can initiate treatment right away while waiting for ejection fraction to be measured,” John McMurray, MD, professor of Medical Cardiology and deputy director of the Institute of Cardiovascular and Medical Sciences at the University of Glasgow, said in the statement.
The DAPA-HF and DELIVER trials were randomized and double-blind to compare dapagliflozin with the placebo. Investigators of each trial enrolled individuals with a diagnosis of HF, functional limitation, and elevated natriuretic peptides.
In the DAPA-HF trial, investigators included individuals with an LVEF of 40% or less. The composite endpoint was time to the first occurrence of a worsening HF event or CV death. The secondary endpoint included the total number of hospitalizations for HF and CV deaths and change from the baseline to 8 months in the total symptom score on the Kansas City Cardiomyopathy Questionnaire (KCCQ).
In the DELIVER trial, individuals with a LVEF greater than 40% were included. Investigators included individuals from across 20 countries in each trial.
The primary endpoint was the time to first occurrence of CV death, hospitalization for HF, or urgent HF visit. The secondary endpoint included the changes from the baseline in the total symptom score of the KCCQ at 8 months, time to the occurrence of CV deaths, time to occurrence of death from any cause, and total number of HF events and CV death.
New data show Farxiga significantly lowers the risk of cardiovascular death in patients with heart failure. News release. AstraZeneca. August 27, 2022. Accessed August 29, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/farxiga-lowers-risk-cv-death-heart-failure.html