KEY POINTS:
- There is a scarcity of treatments for HFpEF and HFmrEF with a high burden of disease worldwide
- In this randomized, double-blind, placebo-controlled trial, finerenone, a non-steroidal MRA, significantly reduced the risk of hospitalization or urgent outpatient visits in patients with HFpEF and HFmrEF compared to placebo in addition to standard of care treatment.
Heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) present a significant global health burden. Dr. Scott Solomon, the lead investigator of the FINEARTS-HF trial from Brigham and Women’s Hospital in Boston Massachusetts, highlighted that nearly half of the 64 million patients with heart failure worldwide fit into this category, indicating a significant unmet need for other treatments. SGLT2 inhibitors are currently the only class 1 therapy for HFpEF and HFmrEF. On September 1st, 2024, the principal results of the “Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction” trial were presented at ESC Congress 2024 with simultaneous publication in New England Journal of Medicine.
While mineralocorticoid receptor antagonists (MRA) have shown clear benefit in heart failure with reduced ejection fraction, the evidence in HFpEF is limited. The TOPCAT trial published in 2014 found that spironolactone did not reduce cardiovascular events in HFpEF. A post-hoc analysis found a benefit in the Americas population that was not replicated in Eastern Europe. Finerenone is different from spironolactone in that it is non-steroidal mineralocorticoid receptor antagonist, and therefore does not have gynecomastia as a side effect.
In this multi-center, randomized, double-blind, placebo-controlled trial, patients with symptomatic heart failure with a left ventricular ejection fraction greater than or equal to 40% were assigned to finerenone or placebo. Eligible patients were randomly assigned (1:1) to finerenone (up to 40 mg once daily depending on baseline estimated glomerular filtration rate [eGFR]) or placebo. The primary endpoint was a composite of total (first and repeat) worsening HF events and cardiovascular death. Secondary endpoints included all-cause mortality and a composite kidney 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 dialysis or kidney transplantation).
In total, 6,001 patients were randomized from more than 650 sites across 37 countries. The mean age was 72 years and 46% were women. The mean LVEF was 53%, the majority had NYHA class II HF (69%) and 20% of patients were enrolled during or within 7 days of a worsening HF event. Compared to patients on placebo group, the finerenone group experienced significantly fewer endpoints (RR 0.084 [95% CI 0.74-0.95], p=0.007) over a median follow up of 32 months. The absolute risk reduction with finerenone amounted to 3.3 events per 100 patient-years. This benefit was observed in all pre-specified groups, including patients taking SGLT2 inhibitors at baseline.
The number of hospitalizations or urgent visits was significantly lower in the finerenone group (RR =0.82, [95% CI 0.70-0.94], p=0.006). However, there was no significant difference in cardiovascular or all-cause mortality between the groups. An improvement in symptoms, as measured by Kansas City Cardiomyopathy Questionnaire Total Symptom Score was observed in the finerenone group. Regarding renal safety, there were more episodes of hyperkalemia and fewer episodes of hypokalemia in the finerenone group. The study was funded by Bayer pharmaceuticals which plans to bring these findings to the FDA for regulatory approval of finerenone.
The principal investigator, Dr Solomon noted: “The FINEARTS-HF trial provides the first definite 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. Given that finerenone was beneficial in patients already receiving an SGLT2 inhibitor, our findings point to finerenone as a new second pillar in HFmrEF/HFpEF.”