DELIVER Trial: Prespecified Analysis Demonstrates Dapagliflozin Benefits Across Subgroups

The DELIVER Trial has provided robust evidence of the benefits of dapagliflozin in patients with heart failure with preserved ejection fraction (HFpEF), according to data revealed by Dr John Ostrominski at the ESC Heart Failure Association’s 2023 scientific sessions1.


The DELIVER trial was conducted by AstraZeneca and presented by Dr John Ostrominski at the ESC HFA 2023 Scientific Sessions. The study has provided robust evidence of the benefits of dapagliflozin, an SGLT2 inhibitor, in patients with heart failure with preserved ejection fraction (HFpEF).


Dapagliflozin is an SGLT2 inhibitor initially developed to improve glycemic control in patients with type 2 diabetes, which had demonstrated beneficial effects in both heart failure and chronic kidney disease. The mechanisms through which dapagliflozin exerts its effects are not fully understood. Interviewing Prof Martin Cowie (Clinical Vice-President AstraZeneca R&D & Honorary Consultant Cardiologist, Guy’s & St Thomas’ NHS Foundation Trust, London, UK), he said that ‘[Dapagliflozin] certainly affects sodium and fluid balance and the way the body holds on to fluid has effects of the kidney level, but it also has effects on the heart […] it’s very beneficial and protects people from the development of heart failure or worsening of heart failure. And we think part of that might be a metabolic switch where the heart becomes more efficient at burning fuel.”2


The DELIVER trial focused on patients with HFpEF, characterized by an ejection fraction above 40% with evidence of structural heart disease and an elevated B-type natriuretic peptide (BNP) level. The trial included over 6,200 patients, with an average age of 72 years followed for an average of 2.3 years. The primary endpoint a combination of cardiovascular mortality and heart failure worsening was reduced by 18% with dapagliflozin


At the ESC Heart Failure 2023 conference, further insights from prespecified subgroup analysis from the DELIVER trial were presented by Dr John Ostrominski. The findings showed that older patients with multiple comorbidities derived significant absolute benefits from dapagliflozin treatment, suggesting consistent benefits across patient subgroups, regardless of the duration of heart failure or the number of comorbidities. The study also showed that as the number of comorbidities increased in the patient, the absolute benefit of dapagliflozin also increased. These results underscored the importance of initiating dapagliflozin therapy regardless of patient characteristics, as the relative and absolute benefits remained consistent.3


The results of the DELIVER trial, along with previous studies such as DAPA HF, have influenced clinical practice guidelines, establishing dapagliflozin as a foundational therapy for heart failure patients, irrespective of ejection fraction. Speaking on the next steps for the trial, Prof Cowie said “we may combine dapagliflozin with other drugs where there's a synergistic effect, whether it's in chronic kidney disease, whether it’s in heart failure or other disease areas […] it's a very exciting time in the field for SGLT2 inhibition.”4.


1. Ostrominski, J, Thierer, J, Vaduganathan, M, et al. Cardio-renal-metabolic overlap, outcomes, and treatment with dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. Presented at HFA in Prague, 20th May, 2023.  

2. Radcliffe Cardiology, Prof Martin Cowie. HFA 23: The DELIVER Phase III Trial.  [Accessed 21.06.2023]

3. Ostrominski, J, Thierer, J, Claggett, BL, et al. Cardio-Renal-Metabolic Overlap, Outcomes, and Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction. JACC Heart Failure, 2023: S2213-1779(23)00251-2.

4. Radcliffe Cardiology, Prof Martin Cowie. HFA 23: The DELIVER Phase III Trial.  [Accessed 21.06.2023]

Article written by Jordan Rance