Influence of background medical therapy on efficacy and safety of dapagliflozin in patients with heart failure with improved ejection fraction in the DELIVER trial

Pabon, M. et al. (2023) Influence of background medical therapy on efficacy and safety of dapagliflozin in patients with heart failure with improved ejection fraction in the DELIVER trial. European Journal of Heart Failure, (doi: 10.1002/ejhf.3001) (PMID:37632711) (Early Online Publication)

Abstract

Aims: The Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial demonstrated the SGLT2i dapagliflozin to be beneficial in patients with symptomatic heart failure with improved ejection fraction (HFimpEF; those with prior LVEF ≤ 40% that had improved to >40% by enrollment). Whether this benefit differs by background medical therapy is unclear. The current study aims to determine the efficacy and safety of dapagliflozin among patients with HFimpEF by background medical therapy. Methods and Results: Treatment effects on the primary endpoint (worsening heart failure or cardiovascular death), were assessed by number of background HF medical therapies (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitor, evidence-based beta blocker, and mineralocorticoid receptor antagonist). Among the 6,263 patients randomized in DELIVER, 1,151 (18%) had HFimpEF. Of those, 21% of patients were on 0-1 therapies, 44% were on 2 therapies, and 35% were on 3 therapies. During 2.3 years of median follow-up, the incidence rate of the primary outcome was 9.7, 8.8, and 8.4 per 100py for patients on 0-1, 2 and 3 HF medications at baseline, respectively. Treatment effects with dapagliflozin on the primary outcome may be greater in patients with HFimpEF on 0-1 therapies at baseline (Pinteraction=0.09), driven mostly by a significant interaction for HF hospitalization (Pinteraction=0.023) with no evidence of effect modification for CV death (Pinteraction=0.65). Treatment effects of dapagliflozin on the primary outcome were, however consistent when assessed across the modified Heart Failure Collaboratory Medical Therapy Score integrating both therapeutic use and dosing (Pinteraction=0.39). The use of dapagliflozin was not associated with changes in use or doses of background HF therapies, and among patients on 3 HF medications at baseline, the addition of dapagliflozin did not lead to higher adverse events. Conclusion: In patients with HFimpEF, the safety and efficacy of dapagliflozin were largely similar by background use and dosing of HF medical therapies. Patients on 0-1 medications at baseline may derive a greater benefit from dapagliflozin in reducing HF events. Among patients already on 3 HF medical therapies, the addition of dapagliflozin was safe without requiring de-escalation of other therapies.

• Item Type: Articles
• Status: Early Online Publication
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jhund, Professor Pardeep and McMurray, Professor John
• Authors: Pabon, M., Claggett, B. L., Wang, X., Miao, Z. M., Chatur, S., Bhatt, A. S., Vaduganathan, M., Fang, J. C., Desai, A. S., Jhund, P., Martinez, F., De Boer, R. A., Kosiborod, M. N., Lam, C. S., Shah, S. J., Hernandez, A. F., McMurray, J. J.V., Solomon, S. D., and Vardeny, O.
• 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 2023
• Publisher Policy: Reproduced under a Creative Commons License