Dapagliflozin and mode of death in heart failure with improved ejection fraction: A post hoc analysis of the DELIVER trial

Vardeny, O. et al. (2024) Dapagliflozin and mode of death in heart failure with improved ejection fraction: A post hoc analysis of the DELIVER trial. JAMA Cardiology, 9(3), pp. 283-289. (doi: 10.1001/jamacardio.2023.5318) (PMID:38265835) (PMCID:PMC10809142)

Abstract

Importance: Heart failure with improved ejection fraction (HFimpEF), defined as prior left ventricular ejection fraction (LVEF) 40% or lower that has increased to greater than 40%, is understudied. Objective: To examine mode of death and the association of dapagliflozin with reductions in cause-specific death in patients with HFimpEF. Design, Setting, and Participants: This was a post hoc analysis from the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) randomized clinical trial, conducted from August 2018 to December 2020. The trial randomly assigned patients with HF with LVEF greater than 40%, New York Heart Association class II to IV symptoms, and elevated natriuretic peptides to treatment with dapagliflozin (10 mg, once daily) or placebo. The presence of HFimpEF was captured through study case report forms. The primary outcome was a composite of worsening HF events (hospitalization or urgent HF visits) or cardiovascular death. Clinical outcomes were adjudicated by a blinded clinical end points committee. Data were analyzed from May 2022 to August 2023. Intervention: Dapagliflozin vs placebo. Main Outcomes and Measures: The mode of death in relation to HFimpEF status was examined, as well as the association of randomized treatment with cause-specific death in Cox regression models. Results: Of 1151 patients with HFimpEF in DELIVER, 190 (16.5%) died, compared with 833 patients (16.3%) of 5112 with LVEF consistently greater than 40%. The overall distribution of mode of death was similar in those with HFimpEF compared with those with LVEF consistently greater than 40% (noncardiovascular death: 103 of 190 [54%] vs 428 of 833 [51%]; cardiovascular death: 87 of 190 [46%] vs 405 of 833 [49%], respectively). Most deaths in individuals with HFimpEF were noncardiovascular (103 of 180 [54%]). For cardiovascular deaths, sudden deaths were most common (36 of 190 events [19%]), followed by HF-related (29 of 190 events [15%]). Among patients with HFimpEF, treatment with dapagliflozin was associated with lower rates of cardiovascular death relative to placebo, a difference primarily due to lower rates of sudden death (hazard ratio, 0.38; 95% CI, 0.18-0.79; P for interaction = .01). Conclusions and Relevance: The findings in this study support current guideline recommendations for use of sodium-glucose transport protein 2 inhibitor therapy, and further suggest that the addition of a sodium-glucose transport protein 2 inhibitor therapy to other guideline-directed medical therapies may help reduce cardiovascular mortality in patients with HFimpEF.

• Item Type: Articles
• Additional Information: Drs Jhund and McMurray are supported by British Heart Foundation Centre of Research Excellence grant RE/18/6/34217 and the Vera Melrose Heart Failure research fund. Dr Petrie is supported by British Heart Foundation Centre of Research Excellence grant RE/18/6/34217.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: UNSPECIFIED
• Authors: Vardeny, O., Desai, A. S., Jhund, P. S., Fang, J. C., Claggett, B., de Boer, R. A., Hernandez, A. F., Inzucchi, S. E., Kosiborod, M. N., Lam, C. S.P., Martinez, F. A., and Shah, S. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: JAMA Cardiology
• Publisher: American Medical Association
• ISSN: 2380-6583
• ISSN (Online): 2380-6591
• Copyright Holders: Copyright: © 2024 Vardeny O et al.
• First Published: First published in JAMA Cardiology 9(3): 283-289
• Publisher Policy: Reproduced under a Creative Commons licence

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303944		BHF Centre of Excellence	Colin Berry	British Heart Foundation (BHF)	RE/18/6/34217	SCMH - Cardiovascular & Metabolic Health