Heart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fraction: insights from DELIVER

Butt, J. H. et al. (2023) Heart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fraction: insights from DELIVER. European Journal of Heart Failure, 25(11), pp. 2078-2090. (doi: 10.1002/ejhf.3000) (PMID:37634087)

Abstract

Introduction: Chronic obstructive pulmonary disease (COPD) is common in heart failure (HF) with a mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and is associated with worse outcomes. Methods and results: In a prespecified analysis of DELIVER, we investigated the relationship between COPD status and outcomes, and the efficacy and safety of dapagliflozin, compared with placebo, according to COPD status. Patients with severe pulmonary disease (including COPD) were excluded from the trial. The primary outcome was a composite of cardiovascular death or worsening HF. Of the 6261 patients with data on baseline COPD status, 694 (11.1%) had a known history of this condition. The risk of the primary endpoint was higher in patients with mild-to-moderate COPD compared with those without COPD (adjusted HR: 1.28 (95% CI: 1.08–1.51). The benefit of dapagliflozin on the primary outcome was consistent irrespective of COPD status: no COPD, HR: 0.82 (95% CI: 0.72–0.93); COPD, HR: 0.82 (95% CI: 0.62–1.10) (Pinteraction = 0.98). Consistent effects were observed for HF, cardiovascular, and all-cause hospitalization, and deaths, and composites of these. Dapagliflozin, as compared with placebo, improved the KCCQ scores from baseline to 8 months to a similar extent in patients with and without mild-to-moderate COPD (Pinteraction ≥0.63). Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of COPD status. Conclusions: Mild-to-moderate COPD is common in patients with HFmrEF/HFpEF and is associated with worse outcomes. The beneficial effects of dapagliflozin compared with placebo on clinical events and symptoms were consistent, regardless of COPD status.

• Item Type: Articles
• Additional Information: The DELIVER trial was funded by AstraZeneca. Profs. McMurray and Jhundare supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217 and the Vera Melrose Heart Failure Research Fund.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Butt, Mr Jawad and Kondo, Dr Toru and Jhund, Professor Pardeep and McMurray, Professor John
• Authors: Butt, J. H., Lu, H., Kondo, T., Bachus, E., de Boer, R. A., Inzucchi, S. E., Jhund, P. S., Kosiborod, M. N., Lam, C. S.P., Martinez, F. A., Vaduganathan, M., Solomon, S. D., and McMurray, J. J.V.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: European Journal of Heart Failure
• Publisher: Wiley
• ISSN: 1388-9842
• ISSN (Online): 1879-0844
• Published Online: 26 August 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in European Journal of Heart Failure 25(11):2078-2090
• Publisher Policy: Reproduced under a Creative Commons license

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