Dapagliflozin significantly reduced the risk of cardiovascular death or worsening of heart failure in patients with mildly reduced or preserved ejection fraction in DELIVER Phase III trial
Detailed results from the DELIVER Phase III trial showed AstraZeneca’s 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 at the European Society of Cardiology Congress 2022 in Barcelona, Spain, and simultaneously published in The New England Journal of Medicine1.
Dapagliflozin 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 dapagliflozin 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. VK Chopra, Senior Director, Cardiac Sciences, Cardiology, Max Super Speciality Hospital, Saket and past president Heart Failure Association of India said: “HFpEF is an underdiagnosed and undertreated condition with high morbidity and mortality. It considered as an orphan therapy area by clinicians as for the last 50 years, limited therapies have shown any benefit in outcomes. DELIVER results helps us to address this huge unmet need and also adds to the evidence that Dapagliflozin is effective in reducing cardiovascular outcomes across the spectrum of heart failure irrespective of ejection fraction.”
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 dapagliflozin 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)2.
Dr. Anil Kukreja, Vice President- Medical Affairs & Regulatory said, “We are committed to push the boundaries of available research and bring the best-in-class solutions for patients. Our ground-breaking results from DELIVER indicates Dapagliflozin’s positive and significant impact on patients with cardiorenal problems. We are constantly enhancing our understanding of the current disease biology with the aim of treating, preventing and even curing complex diseases in near future”.
With a concentrated focus and efforts towards delivery research and science based solution, AstraZeneca’s DapaCare is a robust programme of clinical trials to evaluate the potential CV, renal and organ protection benefits of dapagliflozin. It includes more than 35 completed and ongoing Phase IIb/III trials in more than 35,000 patients, as well as more than 2.5 million patient-years’ experience. Dapagliflozin is currently being tested in patients without T2D following an acute myocardial infarction or heart attack in the DAPA-MI Phase III trial – a first of its kind, indication-seeking registry-based randomised controlled trial.
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 1,2. 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 dapagliflozin as foundational therapy for patients with HF, regardless of ejection fraction.
The safety and tolerability profile of dapagliflozin in the DELIVER Phase III trial was consistent with the well-established safety profile of the medicine.
HF is a chronic, long-term condition that worsens over time3. It affects nearly 64 million people globally, nearly 10 million in India and is associated with substantial morbidity and mortality5,6,14. Chronic HF is the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden6. There are several types of HF often defined by LVEF, a measurement of the percentage of blood leaving the heart each time it contracts, including: HFrEF (LVEF less than or equal to 40%), HFmrEF (LVEF 41-49%) and HFpEF (LVEF greater than or equal to 50%)2. Approximately half of all HF patients have HFmrEF or HFpEF, with few therapeutic options available2,7.
DELIVER was an international, randomised, double-blind, parallel-group, placebo-controlled, event-driven Phase III trial designed to evaluate the efficacy of dapagliflozin , compared with placebo, in the treatment of HF patients with LVEF greater than 40%, with or without T2D. Dapagliflozin was given once daily in addition to background therapy (regional standard of care [SoC] for all comorbidities, including diabetes and hypertension, with the exception of concomitant use of a SGLT2 inhibitor)8. DELIVER is the largest clinical trial to date in HF patients with LVEF above 40%, with 6,263 randomised patients8,9.
The primary endpoint was the time to first occurrence of CV death, hospitalisation for HF (hHF) or an urgent HF visit. The secondary endpoint includes the total number of HF events (hHF or urgent HF visit) and CV death, change from baseline in the total symptom score of the KCCQ at eight months, time to the occurrence of CV death and time to the occurrence of death from any cause8.
AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection and improving outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company’s ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide.