Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure - FINEARTS-HF

Sep 01, 2024
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Author/Summarized by Author:
Amit Saha, MD
Summary Reviewer:
Dharam J. Kumbhani, MD, SM, FACC
Trial Sponsor:
Bayer
Date Presented:
09/01/2024
Date Published:
09/01/2024
Original Posted Date:
09/01/2024
References

Contribution To Literature:

The FINEARTS-HF trial showed that in patients with symptomatic HF with preserved or mildly reduced LVEF, finerenone resulted in a lower composite rate of worsening HF events and CV death compared with placebo.

Description:

The goal of the trial was to determine the efficacy and safety of the nonsteroidal mineralocorticoid antagonist finerenone in patients with heart failure (HF) with preserved or mildly reduced left ventricular ejection fraction (LVEF).

Study Design

  • International
  • Randomized
  • Double-blind

Patients with symptomatic HF and LVEF ≥40% were randomized in a 1:1 fashion to receive finerenone at a maximum dose of 40 mg daily (20 mg if estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2, n = 3,003) or matching placebo (n = 2,998). Finerenone was started at 20 mg daily (10 mg if eGFR <60 mL/min/1.73 m2) and up-titrated after 4 weeks based on potassium levels and if eGFR did not decline ≥30%.

  • Total number of enrollees: 6,001
  • Median follow-up: 32 months
  • Mean patient age: 72 years
  • Percentage female: 46%

Inclusion criteria:

  • Age ≥40 years
  • New York Heart Association (NYHA) class II-IV symptoms
  • LVEF ≥40% within 12 months
  • Left atrial dilation or LV hypertrophy within 12 months
  • N-terminal pro–B-type natriuretic peptide (NT-proBNP) ≥300 pg/mL or BNP ≥100 pg/mL if in sinus rhythm (≥900 pg/mL or ≥300 pg/mL, respectively, if in atrial fibrillation)

Exclusion criteria:

  • eGFR <25 mL/min/1.73 m2
  • Serum/plasma potassium >5.0 mmol/L
  • Myocardial infarction, coronary artery bypass grafting, or stroke ≤90 days prior
  • Percutaneous coronary intervention ≤30 days prior
  • Comorbid conditions that may contribute to dyspnea (e.g., chronic hypoxic respiratory failure from pulmonary disease, hemoglobin <10 g/dL, body mass index ≥50 kg/m2)

Other salient features/characteristics:

  • Mean LVEF: 53%
  • eGFR <60 mL/min/1.73 m2: 48%
  • Mean serum potassium: 4.4 mmol/L
  • NYHA class III-IV symptoms: 31%
  • Sodium-glucose cotransporter-2 (SGLT2) inhibitor use: 14%
  • Type 2 diabetes mellitus: 41%

Principal Findings:

The primary outcome, composite of worsening HF events (first or recurrent unplanned HF hospitalization or urgent visit) and cardiovascular (CV) death, for finerenone vs. placebo, was: 14.9 vs. 17.7 events per 100 patient-years (rate ratio [RR] 0.84, 95% confidence interval [CI] 0.74-0.95, p = 0.007).

Secondary outcomes for finerenone vs. placebo:

  • Worsening HF events: 842 vs. 1,024 events (RR 0.82, 95% CI 0.71-0.94, p = 0.007)
  • CV death: 8.1% vs. 8.7% (hazard ratio [HR] 0.93, 95% CI 0.78-1.11)
  • All-cause mortality: 16.4% vs. 17.4% (HR 0.93, 95% CI 0.83-1.06)
  • Change from baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) score at 12 months: +8.0 vs. +6.4, difference 1.6 (95% CI 0.8-2.3, p < 0.001)
  • Sustained eGFR decrease ≥50% or to <15 mL/min/1.73 m2, new dialysis requirement, or kidney transplantation: 2.5% vs. 1.8% (HR 1.33, 95% CI 0.94-1.89)

Safety outcomes for finerenone vs. placebo:

  • Serum potassium >5.5 mmol/L: 14.3% vs. 6.9%
  • Hyperkalemia resulting in hospitalization: 0.5% vs. 0.2%
  • Serum potassium <3.5 mmol/L: 4.4% vs. 9.7%
  • Systolic blood pressure <100 mm Hg: 18.5% vs. 12.4%

Interpretation:

In patients with HF with preserved or mildly reduced LVEF, the clinical efficacy of finerenone was driven largely by a reduction in first or recurrent worsening HF events, although rates of CV death were numerically also slightly lower compared with placebo. These results are similar in magnitude to those observed in the EMPEROR-PRESERVED and DELIVER trials of SGLT2 inhibitors, which carry a Class 2a indication in the treatment of HF with preserved EF. The benefit of finerenone was similar on prespecified subgroup analyses regardless of SGLT2 inhibitor use or LVEF range above 40%. Although hypothesis-generating, this may nonetheless support the role of dual therapy with both agent classes in this HF population.

It is not clear that finerenone’s efficacy extends to steroidal mineralocorticoid antagonists such as spironolactone, which did not reduce HF events in TOPCAT but may have been affected by regional variability in study protocol implementation. Finally, although FIDELIO-DKD demonstrated reduced progression of diabetic chronic kidney disease with finerenone, the rate of composite kidney events was much lower and therefore perhaps less modifiable in the current study.

References:

Solomon SD, McMurray JJ, Vaduganathan M, et al., for the FINEARTS-HF Committees and Investigators. Finerenone in Heart Failure With Mildly Reduced or Preserved Ejection Fraction. N Engl J Med 2024;Sep 1:[Epub ahead of print].

Presented by Dr. Scott Solomon at the European Society of Cardiology Congress, London, UK, September 1, 2024.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Diuretics, Heart Failure, Mineralocorticoid Receptor Antagonists, ESC Congress, ESC24


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