Effect of dapagliflozin in patients with diabetes and heart failure with mildly reduced or preserved ejection fraction according to background glucose-lowering therapy: A pre-specified analysis of the DELIVER trial

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Mats Christian Højbjerg Lassen
  • John W. Ostrominski
  • Silvio E. Inzucchi
  • Brian L. Claggett
  • Ian Kulac
  • Pardeep Jhund
  • Rudolf A. de Boer
  • Adrian F. Hernandez
  • Mikhail N. Kosiborod
  • Carolyn S.P. Lam
  • Felipe A. Martinez
  • Sanjiv J. Shah
  • Akshay S. Desai
  • Magnus Petersson
  • Anna Maria Langkilde
  • Kieran F. Docherty
  • John J.V. McMurray
  • Scott D. Solomon
  • Muthiah Vaduganathan

Aims: Type 2 diabetes (T2D) and heart failure (HF) frequently coexist, but whether clinical outcomes and treatment effects of sodium–glucose cotransporter 2 inhibitors (SGLT2i) vary in relation to background glucose-lowering therapy (GLT) in this population is uncertain. Methods and results: DELIVER randomized patients with HF and left ventricular ejection fraction (LVEF) >40% to dapagliflozin or placebo. The primary outcome was a composite of worsening HF (HF hospitalization or urgent HF visit) or cardiovascular death. In this pre-specified analysis of participants with T2D, treatment effects were assessed by number and class of background GLT(s). Of 3150 participants with T2D at baseline, 22.9% were on no GLT, 36.5% were treated with 1 GLT, and 40.6% with ≥2 GLTs. During follow-up (median: 2.3 years), treatment benefits of dapagliflozin (vs. placebo) on the primary outcome were consistent irrespective of the number of background GLTs (0 GLTs: hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.50–1.00; 1 GLT: HR 1.04, 95% CI 0.80–1.34; ≥2 GLTs: HR 0.71, 95% CI 0.56–0.90; pinteraction = 0.59). Similar findings were observed among participants with (HR 0.73, 95% CI 0.59–0.92) and without background metformin use (HR 0.89, 95% CI 0.72–1.11; pinteraction = 0.22) and in participants with (HR 0.89, 95% CI 0.69–1.16) and without background insulin use (HR 0.78, 95% CI 0.65–0.95; pinteraction = 0.45). Dapagliflozin was well-tolerated irrespective of the number of background GLTs. Conclusions: Dapagliflozin safely and consistently improved clinical outcomes among individuals with T2D and HF with LVEF >40% irrespective of the number and class of background GLTs, and the benefits were not influenced by concomitant metformin or insulin use. These data bolster contemporary guidelines supporting first-line SGLT2i among individuals with T2D and HF, irrespective of background GLT.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Heart Failure
ISSN1388-9842
DOI
StatusE-pub ahead of print - 2024

Bibliografisk note

Funding Information:
The DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) was funded by AstraZeneca. AstraZeneca was involved in the overall design and conduct of the trials and collection, management, and interpretation of the data but had no role in the drafting and preparation of the manuscript, or decision to submit the manuscript for publication. Coauthors who are employees of AstraZeneca reviewed and approved the manuscript in accordance with authorship guidelines.

Publisher Copyright:
© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

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