Support for finerenone to treat HF in patients with ejection fractions above 40%

medwireNews: The FINEARTS-HF trial has shown a reduced risk for cardiovascular death and heart failure (HF) events with finerenone use in people with HF and a mildly reduced or preserved ejection fraction. Scott Solomon (Brigham and Women’s Hospital, Boston, Massachusetts, USA) explained to delegates at the ESC Congress 2024 in London, UK, that “finerenone is a nonsteroidal MRA [mineralocorticoid receptor antagonist] which, compared with steroidal MRAs, is more selective for the MR receptor, has a shorter half-life, and has a more balanced distribution between the heart and the kidney.” The study was also simultaneously published in The New England Journal of Medicine. Solmon and team randomly assigned 6016 patients with symptomatic HF (New York Heart association [NYHA] class II–V; 69% class II) and a left ventricular ejection fraction of at least 40% (mean 53%) to receive once daily finerenone or placebo in addition to usual therapy. This included loop diuretics in 87% of patients in each group and beta blockers in 85%. Sodium-glucose cotransporter (SGLT)2 inhibitors were being taken by 13% of patients in the finerenone group and 14% in the placebo group. Finerenone was given at a dose of up to 40 mg based on baseline estimated glomerular filtration rate (eGFR ≤60 mL/min target 20 mg; >60 m/L/min target 40 mg), with uptitration to the maximum tolerated dose when potassium levels were below 5.0 mmol/L and eGFR had decreased to below 30%. The patients were aged a mean of 72 years, around 55% were men, and the majority (79%) were White. All the patients had elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, at a median of 1052 ng/L in the finerenone group and 1028 ng/L in the placebo group. Solomon noted that 20% of patients were randomly assigned to treatment during or within 7 days of a worsening HF event, 34% between 7 days and 3 months of an event, and 46% more than 3 months after or had no prior worsening HR event. Over a median follow-up of 32 months, finerenone treatment was associated with a significant 16% reduction in the rate of the primary endpoint of cardiovascular death or total worsening HF events, and an absolute reduction of 3.3 per 100 patient–years. In all, there were 1083 events among the 3003 patients in the finerenone arm versus 1283 among the 2998 patients in the placebo arm, translating to 14.3 and 17.6 events per 100 patient–years, respectively. “Treatment effects were consistent across all prespecified subgroups,” said Solomon, including patients with an eGFR above and below 60 mL/min per 1.73 m2 at baseline and those taking and not taking SGLT2 inhibitors. With regard to secondary endpoints, there was a significant 18% reduction in the rate of total HF events with finerenone versus placebo, and a numerical but nonsignificant 7% reduction in both the risk for cardiovascular and all-cause death. There was also a significant 1.6-point improvement in the Kansas City Cardiomyopathy Questionnaire-Total Symptom Score at 12 months, with scores in the finerenone-treated patients increasing by 8.0 points from baseline versus 6.4 points in the placebo-treated group. However, there was no significant difference in the percentage of patients whose NYHA class had improved at 12 months (18.6 vs 18.4%) nor in the rate of the small number of the composite renal outcome of sustained decrease in eGFR to 50% or above relative to baseline, a sustained decline to less than 15 mL/min per 1.73 m2, or renal failure (2.5 vs 1.8%). The presenter reported that finerenone was “well tolerated,” with a similar number of serious adverse events across the two groups, at 38.7% with finerenone and 40.5% with placebo. He pointed out that, “as seen with every MRA tested,” there was evidence of more hyperkalemia with finerenone than placebo, with serum potassium levels above 5.5 mmol/L in 14.3% versus 6.9% of patients. But there were “very, very few episodes of hyperkalemia leading to hospitalization,” at 0.5% versus 0.2%, and no episodes leading to death. Levels of hypokalemia (<3.5 mmol/L), on the other hand, were lower with finerenone than placebo (4.4 vs 9.7%). Solmon concluded that “the data support the use of finerenone in patients with heart failure with mildly reduced or preserved ejection fraction.” Discussant Theresa McDonagh (King’s College Hospital, London, UK) considered what the findings might mean for guidelines in HF with mild and preserved ejection fraction. “Currently, the ESC guidelines give a weak recommendation for MRA use for mildly reduced ejection fraction […] and we give no recommendations for HFpEF [heart failure with preserved ejection fraction],” she said. “The US guidelines do give a recommendation for HFpEF.” McDonagh continued: “I think we can see a stronger recommendation for MRAs and finerenone in this space going forward, at least class IIa, of course depending on other studies that report in the interim.” In terms of clinical practice, she commented that there is now “another option to give patients with ejection fractions above 40% in addition to SGLT2 inhibitors, and this trial definitely fulfills an unmet need.” medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group ESC Congress 2024; London, UK: 30 August–2 September N Engl J Med 2024; doi:10.1056/NEJMoa2407107

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Support for finerenone to treat HF in patients with ejection fractions above 40%

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