New findings from a pre-specified analysis of DELIVER Phase III trial data show that AstraZeneca’s Farxiga (dapagliflozin) improved symptom burden and health-related quality of life in patients with heart failure (HF) and mildly reduced or preserved ejection fraction (EF) compared with placebo1. The results were presented today at the American Heart Association (AHA) Scientific Sessions 2022 in Chicago, Illinois, US, and are currently in press in the Journal of the American College of Cardiology.
In addition to the greater risk of death and hospitalisations, patients with HF and mildly reduced or preserved EF experience an especially high burden of symptoms and physical limitations, and a poor quality of life, which is why improving health status is a key goal of management1. In a prespecified analysis of the DELIVER Phase III trial, the Kansas City Cardiomyopathy Questionnaire (KCCQ) was utilised to examine the effects of Farxiga on a broad range of health outcomes.
In the analysis, Farxiga, in addition to standard care compared with placebo, improved symptom burden, physical limitations and quality of life as measured by mean KCCQ scores, with benefits achieved as early as one month. Benefits were sustained at eight months, with mean improvement in total symptom score of 2.4 points, physical limitations 1.9 points, clinical summary 2.3 points and overall summary 2.1 points higher than placebo (all p <0.001). Also at eight months, fewer patients treated with Farxiga compared to placebo had a significant deterioration, and more had at least small, moderate and large (at least 5-, at least 10- and at least 15-point, respectively) improvements in health status across evaluated KCCQ domains1. The benefits of Farxiga on cardiovascular (CV) death and worsening HF in patients with mildly reduced or preserved EF appeared especially pronounced in those with greater degree of symptomatic impairment at baseline.
Dr. Mikhail Kosiborod, cardiologist at Saint Luke’s Mid America Heart Institute, Vice President of Research at Saint Luke’s Health System, Professor of Medicine at the University of Missouri-Kansas City, said: “Many patients living with heart failure value their symptoms and physical function at least equally with avoidance of death, making these results highly clinically relevant. Given the fact that individuals with heart failure and mildly reduced and preserved ejection fraction experience especially poor health status, the findings should prompt clinicians to strongly consider initiation of SGLT2 inhibitors in this group, particularly if patients are symptomatic.”
The results support the 2022 joint HF guidelines issued by the American College of Cardiology, the American Heart Association and the Heart Failure Society of America, recommending broader use of sodium-glucose cotransporter 2 (SGLT2) inhibitors in clinical practice and earlier initiation of guideline-directed medical therapy.
Furthermore, these data align with the recent JAMA Cardiology publication, Time to Clinical Benefit of Dapagliflozin in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Prespecified Secondary Analysis of the DELIVER Randomized Clinical Trial, which demonstrated early and sustained reductions in clinical events in patients with HF and mildly reduced or preserved EF with statistically significant benefits observed within two weeks of treatment initiation.
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Recently Farxiga became the first heart failure medication ever to demonstrate mortality benefit across the full ejection fraction range, and now we also have data from the DELIVER trial showing that the health-related quality of life of patients with heart failure is significantly improved. Coupled with the rapid clinical benefits seen within two weeks, the data support the use of Farxiga as foundational therapy and highlight key opportunities for clinicians to implement the guidelines and upgrade patient outcomes.”
