Finerenone reduced heart failure (HF) events and cardiovascular death in patients with heart failure and mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF), according to the latest research presented in a Hot Line session today at ESC Congress 2024 .
Explaining the rationale behind the trial, principal investigator Professor Scott Solomon of Brigham and Women’s Hospital, Boston, USA, said: “Sodium-glucose co-transporter 2 (SGLT2) inhibitors are the only treatment for HFmrEF/HFpEF with strong guideline recommendation and there remains a great unmet need for additional therapies to improve morbidity and mortality in this large patient population Steroid mineralocorticoid receptor antagonists (MRAs) have proven benefits in heart failure with reduced ejection fraction (HFrEF), but their efficacy in HFmrEF/HFpEF. It has not been definitively documented. We investigated the nonsteroidal MRA, finerenone, in patients with HFmrEF/HFpEF in the FINEARTS-HF trial and a significant positive effect on outcomes was observed.
FINEARTS-HF was a double-blind, randomized trial in patients with heart failure (New York Heart Association [NYHA] functional class II-IV) and a left ventricular ejection fraction (LVEF) of 40% or greater. Additional inclusion criteria included age 40 years or older, elevated natriuretic peptides, and evidence of structural heart disease.
Eligible patients were randomized (1:1) to finerenone (up to 40 mg once daily according to estimated baseline glomerular filtration rate [eGFR]) or placebo. The primary endpoint was a composite of total (first and recurrent) worsening of HF events and cardiovascular death. Secondary endpoints included all-cause mortality and composite renal outcome (sustained 50% or greater decline in eGFR, sustained decline in eGFR to less than 15 ml/min/1.73 m2, or initiation of chronic hemodialysis or renal transplantation).
In total, 6,001 patients were randomized from more than 650 sites in 37 countries. The mean age was 72 years and 46% were women. Mean LVEF was 53%, the majority had NYHA class II HF (69%), and 20% of patients were enrolled during or within 7 days of worsening of an HF episode.
At a median of 32 months, finerenone significantly reduced the primary endpoint, with 1,083 events in the finerenone group and 1,283 events in the placebo group (odds ratio 0.84, 95% confidence interval [CI] 0.74-0.95; p=0.007). A significant reduction in overall worsening of heart failure events was seen with finerenone compared with placebo (842 vs 1,024 events, rate ratio 0.82, 95% CI 0.71-0.94, p=0.006). Cardiovascular death was nonsignificantly reduced in the finerenone arm (8.1% and 8.7%, hazard ratio [HR] 0.93; 95% CI 0.78–1.11). Primary outcome results were consistent across prespecified subgroups, including those based on ejection fraction or baseline use of SGLT2 inhibitors.
There was no difference between the finerenone and placebo groups for all-cause mortality (16.4% and 17.4%, respectively; HR 0.93, 95% CI 0.83–1.06) or the composite renal outcome (2.5% and 1.8%, respectively, HR 1.33 95% CI 0.94-1.89).
Serious adverse events were similar between groups (finerenone: 38.7%, placebo: 40.5%). Finerenone increased the risk of investigator-reported hyperkalemia (9.7% vs. 4.2%) but decreased the risk of hypokalemia (4.4% vs. 9.7%).
The FINEARTS-HF trial provides the first clear evidence that an MRA is beneficial in HFmrEF/HFpEF. We have four pillars of guideline-directed medical therapy in HFrEF, but only SGLT2 inhibitors as a treatment option for HFmrEF/HFpEF. Since finerenone was beneficial in patients already receiving an SGLT2 inhibitor, our findings point to finerenone as a new second pillar in HFmrEF/HFpEF.”
Professor Scott Solomon, Brigham and Women’s Hospital, Boston, USA
