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Achieved Ejection Fraction and Effects of Dapagliflozin in Heart Failure With Improved Ejection Fraction.

Publication ,  Journal Article
Siqueira, SRO; Pabon, MA; Vaduganathan, M; Claggett, BL; Lam, CSP; Kosiborod, MN; de Boer, RA; Shah, SJ; Fang, JC; Desai, AS; Jhund, PS ...
Published in: JACC Heart Fail
October 2025

BACKGROUND: Patients with heart failure with improved ejection fraction (HFimpEF) remain understudied and face residual risks comparable with those with a left ventricular ejection fraction (LVEF) consistently >40% (no prior heart failure with reduced ejection fraction). The implications of achieved LVEF after improvement on prognosis and treatment response remains unclear. OBJECTIVES: This study examines whether the degree of LVEF improvement influences prognosis and the therapeutic effects of dapagliflozin in HFimpEF. METHODS: The DELIVER trial randomized patients with heart failure and LVEF >40% to dapagliflozin or placebo, including those with HFimpEF. In the HFimpEF subset, we examined the association between baseline LVEF (≤49% [reference group], 50%-59%, and ≥60%) and the primary outcome (worsening HF or cardiovascular death) and whether the degree of LVEF improvement modified the treatment response to dapagliflozin. RESULTS: Of 6,263 participants, 1,151 (18%) had HFimpEF: 624 (54%), 328 (29%), and 199 (17%) had improved LVEF at baseline of ≤49%, 50%-59%, and ≥60%, respectively. Over a median follow-up of 2.3 years, primary outcome rates (per 100 person-years) in HFimpEF vs LVEF consistently >40% were 9.9 vs 10.5 (≤49%), 6.7 vs 8.4 (50%-59%), and 9.3 vs 7.5 (≥60%). Dapagliflozin safely and consistently reduced the risk of the primary outcome across LVEF groups (P for interaction = 0.19). CONCLUSIONS: In patients with HFimpEF, the efficacy and safety of dapagliflozin in reducing cardiovascular death or worsening HF events were consistent irrespective of the degree of LVEF improvement before enrollment, including in those who achieve an LVEF ≥60% who appear to face significant residual risks of clinical events. (Dapagliflozin Evaluation to Improve the LIVEs of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).

Duke Scholars

Published In

JACC Heart Fail

DOI

EISSN

2213-1787

Publication Date

October 2025

Volume

13

Issue

10

Start / End Page

102585

Location

United States

Related Subject Headings

  • Ventricular Function, Left
  • Treatment Outcome
  • Stroke Volume
  • Sodium-Glucose Transporter 2 Inhibitors
  • Prognosis
  • Middle Aged
  • Male
  • Humans
  • Heart Failure
  • Glucosides
 

Citation

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Siqueira, S. R. O., Pabon, M. A., Vaduganathan, M., Claggett, B. L., Lam, C. S. P., Kosiborod, M. N., … Vardeny, O. (2025). Achieved Ejection Fraction and Effects of Dapagliflozin in Heart Failure With Improved Ejection Fraction. JACC Heart Fail, 13(10), 102585. https://doi.org/10.1016/j.jchf.2025.102585
Siqueira, Sara R. O., Maria A. Pabon, Muthiah Vaduganathan, Brian L. Claggett, Carolyn S. P. Lam, Mikhail N. Kosiborod, Rudolf A. de Boer, et al. “Achieved Ejection Fraction and Effects of Dapagliflozin in Heart Failure With Improved Ejection Fraction.JACC Heart Fail 13, no. 10 (October 2025): 102585. https://doi.org/10.1016/j.jchf.2025.102585.
Siqueira SRO, Pabon MA, Vaduganathan M, Claggett BL, Lam CSP, Kosiborod MN, et al. Achieved Ejection Fraction and Effects of Dapagliflozin in Heart Failure With Improved Ejection Fraction. JACC Heart Fail. 2025 Oct;13(10):102585.
Siqueira, Sara R. O., et al. “Achieved Ejection Fraction and Effects of Dapagliflozin in Heart Failure With Improved Ejection Fraction.JACC Heart Fail, vol. 13, no. 10, Oct. 2025, p. 102585. Pubmed, doi:10.1016/j.jchf.2025.102585.
Siqueira SRO, Pabon MA, Vaduganathan M, Claggett BL, Lam CSP, Kosiborod MN, de Boer RA, Shah SJ, Fang JC, Desai AS, Jhund PS, Inzucchi SE, Martinez F, Hernandez AF, Petersson M, McMurray JJV, Solomon SD, Vardeny O. Achieved Ejection Fraction and Effects of Dapagliflozin in Heart Failure With Improved Ejection Fraction. JACC Heart Fail. 2025 Oct;13(10):102585.
Journal cover image

Published In

JACC Heart Fail

DOI

EISSN

2213-1787

Publication Date

October 2025

Volume

13

Issue

10

Start / End Page

102585

Location

United States

Related Subject Headings

  • Ventricular Function, Left
  • Treatment Outcome
  • Stroke Volume
  • Sodium-Glucose Transporter 2 Inhibitors
  • Prognosis
  • Middle Aged
  • Male
  • Humans
  • Heart Failure
  • Glucosides