Dapagliflozin in heart failure with improved ejection fraction: a prespecified analysis of the DELIVER trial

Orly Vardeny, James C. Fang, Akshay S. Desai, Pardeep S. Jhund, Brian Claggett, Muthiah Vaduganathan, Rudolf A. de Boer, Adrian F. Hernandez, Carolyn S.P. Lam, Silvio E. Inzucchi, Felipe A. Martinez, Mikhail N. Kosiborod, David DeMets, Eileen O’Meara, Shelley Zieroth, Josep Comin-Colet, Jaroslaw Drozdz, Chern En Chiang, Masafumi Kitakaze, Magnus PeterssonDaniel Lindholm, Anna Maria Langkilde, John J.V. McMurray, Scott D. Solomon

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


With modern treatments for heart failure with reduced ejection fraction (EF), indicative of impaired cardiac systolic function, patients may exhibit an increase in EF. Limited data are available regarding the clinical management of this growing population, categorized as heart failure with improved EF (HFimpEF), which has a high event rate and has been excluded from virtually all prior heart failure outcomes trials. In a prespecified analysis of the DELIVER trial (NCT03619213), of a total of 6,263 participants with symptomatic heart failure and a left ventricular EF >40%, 1,151 (18%) had HFimpEF, defined as patients whose EF improved from ≤40% to >40%. Participants were randomized to 10 mg dapagliflozin or placebo daily and the primary outcome of the trial was a composite of cardiovascular death or worsening heart failure (heart failure hospitalization or an urgent heart failure visit). Participants with HFimpEF had similar event rates to those with an EF consistently >40%. In participants with HFimpEF, dapagliflozin reduced the primary composite outcome (hazard ratio (HR) = 0.74, 95% confidence interval (CI) = 0.56–0.97), first worsening heart failure events (HR = 0.78, 95% CI = 0.61–1.14), cardiovascular death (HR = 0.62, 95% CI = 0.41–0.96) and total worsening heart failure events (rate ratio = 0.68, 95% CI = 0.50–0.94) to a similar extent as for individuals with an EF consistently >40%. These data suggest that patients with HFimpEF who are symptomatic may benefit from the addition of a sodium/glucose cotransporter 2 inhibitor to previously instituted guideline-directed medical therapy to further reduce morbidity and mortality.

Original languageEnglish (US)
Pages (from-to)2504-2511
Number of pages8
JournalNature Medicine
Issue number12
StatePublished - Dec 2022

Bibliographical note

Funding Information:
AstraZeneca was the sponsor and funder of the DELIVER trial. AstraZeneca had organizational oversight over the DELIVER trial and was responsible for trial conduct, supervision and monitoring of the enrolling centers, data collection and storage. The trial was designed by the academic members of the executive committee in cooperation with the sponsor. Data analysis of each trial was performed by AstraZeneca according to the SAP and an independent academic statistician at the Brigham and Women’s Hospital, Boston. Data analysis of the present study was conducted by the independent academic group at Brigham and Women’s Hospital and verified by the sponsor.

Publisher Copyright:
© 2022, The Author(s).


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