FINEARTS-HF - finerenone in heart failure with mildly reduced or preserved ejection fraction

Finerenone is a selective mineralocorticoid receptor (MR) blocker:

• inhibits the effects of mineralocorticoids like aldosterone and cortisol when the MR is overactivated

FINEARTS-HF study

• double-blind trial
• randomly assigned patients with heart failure and a left ventricular ejection fraction of 40% or greater, in a 1:1 ratio, to receive finerenone (at a maximum dose of 20 mg or 40 mg once daily) or matching placebo, in addition to usual therapy
• primary outcome was a composite of total worsening heart failure events (with an event defined as a first or recurrent unplanned hospitalization or urgent visit for heart failure) and death from cardiovascular causes

Study results:

• over a median follow-up of 32 months, 1083 primary-outcome events occurred in 624 of 3003 patients in the finerenone group, and 1283 primary-outcome events occurred in 719 of 2998 patients in the placebo group (rate ratio, 0.84; 95% confidence interval [CI], 0.74 to 0.95; P=0.007)
• total number of worsening heart failure events was 842 in the finerenone group and 1024 in the placebo group (rate ratio, 0.82; 95% CI, 0.71 to 0.94; P=0.006)
• percentage of patients who died from cardiovascular causes was 8.1% and 8.7%, respectively (hazard ratio, 0.93; 95% CI, 0.78 to 1.11). Finerenone was associated with an increased risk of hyperkalemia and a reduced risk of hypokalemia

Study authors concluded that:

• patients with heart failure and mildly reduced or preserved ejection fraction, finerenone resulted in a significantly lower rate of a composite of total worsening heart failure events and death from cardiovascular causes than placebo

An analysis of FINEARTS-HF found those with recent worsening heart failure event had a higher risk of recurrent heart failure events/CV death, & the absolute benefit of finerenone may be higher in these patients (2).

An analysis showed that in FINEARTS-HF, a population at low risk of adverse kidney outcomes, finerenone did not significantly modify the kidney composite outcomes (3):

• finerenone led to a greater reduction in initial eGFR, but did not result in a significant difference in chronic eGFR slope vs placebo
• finerenone led to early and sustained reductions in albuminuria and reduced the risk of new-onset micro- and macroalbuminuria

Finerenone and new onset type 2 diabetes:

• in study (n=6001 with NYHA functional class II–IV, LVEF ≥ 40%, evidence of structural heart disease, and elevated NT-pro BNP levels) use of finerenone was linked to relative reduction in new-onset diabetes of 24% compared to placebo (hazard ratio 0.76 [95% CI 0.59–0.97], p=0.026) (4)

Reference:

1. Solomon SD et al. Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. NEJM September 1, 2024.
2. Desai AS et al. Finerenone in Patients With a Recent Worsening Heart Failure Event: The FINEARTS-HF Trial. JACC 29 September 2024.
3. McCausland FR et al. Finerenone and Kidney Outcomes in Patients With Heart Failure: The FINEARTS-HF Trial. JACC January 21st 2025.
4. Butt, Jawad H et al. Finerenone and new-onset diabetes in heart failure: a prespecified analysis of the FINEARTS-HF trial. Lancet Diabetes and Endocrinology January 13th 2025.