Lifetime benefits of comprehensive medical therapy in heart failure with mildly reduced or preserved ejection fraction
This week, we would like to present the article: « Lifetime benefits of comprehensive medical therapy in heart failure with mildly reduced or preserved ejection fraction », recently published in Nature Medicine and co-authored with one of our Advisory Board members Faiez Zannad.
❤️ Individual improvement in events related to heart failure (HF) with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF) has been demonstrated with the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the nonsteroidal mineralocorticoid receptor antagonist (nsMRA) finerenone. In addition, in patients with HF, the use of an angiotensin and neprilysin receptor inhibitor (ARNI) improves these outcomes.
❤️ However, the question posed by the authors of this paper is whether there is an expected benefit from the combined use of these agents in the long-term treatment of HFmrEF)/HFpEF.
❤️ The DELIVER, FINEARTS-HF, and PARAGON-HF trials have provided comprehensive data on HF, and cross-analysis of the combined use of treatments shows that the combination of SGLT2i and nsMRA reduces the risk of CV death or first HF worsening by 31% in the overall population, while the combined use of SGLT2i, nsMRA, and ARNI reduces the risk by 39% in patients with HFmrEF)/HFpEF.
❤️ Therefore, long-term use of combined SGLT2i and nsMRA therapy in a 65-year-old patient with HFmrEF/HFpEF, or combined SGLT2i, nsMRA and ARNI in a 65-year-old patient with LVEF < 60% should result in long-term gains of 3.6 (2.0-5.2) or 4.9 (2.5-7.3) additional years without CV death or HF events, respectively.
❤️ It should be noted that combination therapy is expected to result in significant gains in event-free survival across a wide age range, from 55 to 85 years of age, which is a considerable advance, as are the potential long-term cumulative effects of early combination medical therapy with SGLT2i and nsMRA (and ARNI in some individuals) in patients with HFmrEF)/HFpEF.
@Muthiah Vaduganathan, Brian Claggett , Safia Chatur, @Akshay S. Desai, Pardeep Jhund, Orly Vardeny, Béla Merkely MD, PhD, Felipe Martinez, Josep Comin-colet, @José Francisco Kerr Saraiva, @Sanjiv J. Shah, @Carolyn S. P. Lam, Faiez Zannad, Kieran Docherty, @John J. V. McMurray, @Scot D Solomon.
Nat Med. 2026 Jan;32(1):325-331. doi: 10.1038/s41591-025-04037-3. Epub 2025 Oct 6. PMID: 41052644; PMCID: PMC12823412.
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