LONDON: Detailed results from the DELIVER Phase III trial showed AstraZeneca’s Farxiga (dapagliflozin) significantly reduced the composite of cardiovascular (CV) death or worsening heart failure (HF) in patients with HF and mildly reduced or preserved ejection fraction (EF), compared to placebo.
The results were presented today at the European Society of Cardiology Congress 2022 in Barcelona, Spain, and simultaneously published in The New England Journal of Medicine1.
Farxiga reduced the composite outcome of CV death or worsening of HF by 18% (p<0.001, 16.4% in the dapagliflozin group and 19.5% in the placebo group over a median follow-up of 2.3 years). All individual components contributed to the superiority of the primary endpoint. The findings were consistent across key subgroups examined and extend the benefits of Farxiga to the full spectrum of patients with HF irrespective of left ventricular ejection fraction (LVEF) status. The trial results also showed a symptom benefit in patient-reported outcomes measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score1.
Dr. Scott Solomon, Professor of Medicine at Harvard Medical School and Brigham and Women’s Hospital and Principal Investigator of the DELIVER Phase III trial, said: “These results from DELIVER are important for patients and clinical care as it shows that dapagliflozin is effective regardless of ejection fraction and therefore can be used as foundational therapy in all eligible patients with heart failure. Earlier HFpEF trials have shown attenuation in the highest LVEF but with dapagliflozin results are consistent across the LVEF range. The findings also reinforce most recent treatment guidelines, recommending earlier initiation of guideline-directed medical treatment and may support broader use of SGLT2 inhibitors in clinical practice.”
The updated 2022 joint HF guidelines issued by the American College of Cardiology, the American Heart Association and the Heart Failure Society of America, now recommend sodium-glucose cotransporter 2 (SGLT2) inhibitors such as Farxiga for HF with mildly reduced EF (HFmrEF) and HF with preserved EF (HFpEF). This expands upon previous recommendations supporting the use of SGLT2 inhibitors in HF with reduced EF (HFrEF).
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Heart failure patients with LVEF greater than 40% are the most difficult to treat with few treatment options available to them. We are proud to share the groundbreaking DELIVER results, which have expanded our understanding of the complexities of HF. These data build upon our previous studies demonstrating cardiorenal protection of Farxiga across patients with type-2 diabetes, chronic kidney disease and heart failure.”
DELIVER was designed with broader inclusion criteria than prior trials in this patient population to also include patients who were hospitalised, recently hospitalised, or those with HF with improved LVEF, for whom evidence-based therapy is limited.
These findings build upon the previously reported results from DAPA-HF, the only SGLT2 inhibitor outcomes trial in HF to demonstrate a significant reduction in mortality, to provide further evidence to support the use of Farxiga as foundational therapy for patients with HF, regardless of ejection fraction.
The safety and tolerability profile of Farxiga in the DELIVER Phase III trial was consistent with the well-established safety profile of the medicine.