Dapagliflozin in patients with heart failure with mildly reduced and preserved ejection fraction treated with a mineralocorticoid receptor antagonist or sacubitril/valsartan

Mingming Yang, Jawad H. Butt, Toru Kondo, Karola S. Jering, Kieran F. Docherty, Pardeep S. Jhund, Rudolf A. de Boer, Brian L. Claggett, Akshay S. Desai, Adrian F. Hernandez, Silvio E. Inzucchi, Mikhail N. Kosiborod, Carolyn S.P. Lam, Anna Maria Langkilde, Felipe A. Martinez, Magnus Petersson, Sanjiv J. Shah, Muthiah Vaduganathan, Ulrica Wilderäng, Scott D. SolomonJohn J.V. McMurray*

*Corresponding author for this work

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Abstract

Aims: The effects of adding a sodium–glucose cotransporter 2 (SGLT2) inhibitor to a mineralocorticoid receptor antagonist (MRA) or an angiotensin receptor–neprilysin inhibitor (ARNI) in patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) are uncertain, even though the use of all three drugs is recommended in recent guidelines. Methods and results: The efficacy and safety of dapagliflozin added to background MRA or ARNI therapy was examined in patients with HFmrEF/HFpEF enrolled in the DELIVER trial. The primary outcome was the composite of worsening HF or cardiovascular death. Of 6263 patients, 2667 (42.6%) were treated with an MRA and 301 (4.8%) with an ARNI at baseline. Patients taking either were younger, more often men and had lower systolic blood pressure and ejection fraction; they were also more likely to have prior HF hospitalization. The benefit of dapagliflozin was similar whether patients were receiving these therapies. The hazard ratio for the effect of dapagliflozin compared to placebo on the primary outcome was 0.86 (95% confidence interval [CI] 0.74–1.01) for MRA non-users versus 0.76 (95% CI 0.64–0.91) for MRA users (pinteraction = 0.30). The corresponding values for ARNI non-users and users were 0.82 (95% CI 0.73–0.92) and 0.74 (95% CI 0.45–1.22), respectively (pinteraction = 0.75). None of the adverse events examined was more common with dapagliflozin compared to placebo overall or in the MRA and ARNI subgroups. Conclusions: The efficacy and safety of dapagliflozin were similar, regardless of background treatment with an MRA or ARNI. SGLT2 inhibitors may be added to other treatments recommended in recent guidelines for HFmrEF/HFpEF.

Original languageEnglish
Pages (from-to)2307-2319
Number of pages13
JournalEuropean Journal of Heart Failure
Volume24
Issue number12
Early online date7 Nov 2022
DOIs
Publication statusPublished - Dec 2022

Bibliographical note

Funding Information:
John J.V. McMurray is supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217. Mingming Yang is funded by the China Scholarship Council. The DELIVER trial was funded by AstraZeneca.

Publisher Copyright:
© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

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