Finerenone Enhances Outcomes in Obese HFpEF Patients: Insights from FINEARTS-HF Analysis

 Patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and high BMI experience greater benefits from finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), compared to those with normal or low BMI.

When stratified by BMI categories, finerenone showed a reduction in cardiovascular (CV) deaths and worsening HF events across all weight groups compared to placebo.

An analysis of BMI as a continuous variable revealed that patients with BMI ≥ 35 experienced the most substantial benefits.

This supports earlier findings from trials like RALES and EMPHASIS-HF, which suggested that MRAs benefit patients with obesity more significantly due to increased aldosterone secretion and mineralocorticoid receptor overactivation.

Patients with HFpEF have a higher prevalence of obesity compared to those with HFrEF.

The findings refute the concept of an obesity paradox in HFpEF, aligning with prior evidence in HFrEF from the PARADIGM-HF and DANISH trials.

Experts emphasize that weight loss is crucial for obese patients with HFpEF to improve outcomes.

Finerenone use is recommended across all BMI categories, with more confidence in its benefits for patients with severe obesity.

The underlying mechanism of obesity-related HFpEF remains unclear but may involve volume overload from elevated aldosterone levels.

Given that two-thirds of HFpEF patients in the U.S. have obesity, combining MRAs like finerenone with GLP-1 receptor agonists may optimize weight loss and reduce HF events.

Further research is ongoing to evaluate the additive effects of MRAs and GLP-1 receptor agonists.

The main FINEARTS-HF trial included 6,001 patients with symptomatic HF and LVEF ≥ 40%.

Patients receiving 20-40 mg of finerenone daily showed a significant reduction in HF events but no major difference in CV death compared to placebo.

BMI-based analysis categorized patients into five groups, from underweight/normal weight to obesity class III (BMI ≥ 40).

Higher BMI patients tended to be younger, female, and sicker, with worse quality of life and symptom severity scores.

Despite higher illness severity, obese patients had lower NT-proBNP levels, a marker of HF stress.

Editorialists argue for moving beyond BMI as a measure of obesity, suggesting inclusion of metabolic consequences and measures like waist-to-height ratio.

Efforts are underway to define obesity-related HFpEF more precisely to improve targeted treatment strategies.

Take-Home Points:

1. Finerenone is effective across all BMI groups but shows greater benefits in severely obese patients.
2. Obesity in HFpEF exacerbates aldosterone-related HF stress, making MRAs highly effective.
3. Combining MRAs like finerenone with GLP-1 receptor agonists may further optimize outcomes in obese patients.
4. Standard BMI metrics are flawed for defining obesity, and alternative measures like waist-to-height ratio are being explored.
5. Addressing obesity in HFpEF patients is critical to improve cardiometabolic health and reduce HF events.