Finerenone Maintains Benefits in HFmrEF, HFpEF Regardless of Frailty Status

Findings from a prespecified analysis of the FINEARTS-HF trial suggest the beneficial effects of finerenone on reducing the risk of total worsening heart failure (HF) events and cardiovascular death and on improving symptoms were not modified by frailty status, challenging the notion that newer HF treatments present a less favorable benefit-risk profile in patients with frailty.1

Results showed that although frailty was common in patients with HF and mildly reduced ejection fraction (HFmrEF) or HF and preserved ejection fraction (HFpEF) and greater frailty was associated with more impairment in health status and worse clinical outcomes, the beneficial effects of treatment with finerenone were not impacted by frailty.1

“There has been increasing interest in investigating the efficacy and safety of new HF treatments according to frailty status due to concerns that individuals with frailty obtain less benefit from evidence-based therapies, have more treatment intolerance, experience more adverse drug reactions and drug interactions, and are more likely to discontinue treatment than nonfrail patients,” John McMurray OBE, BSC (Hons), MB ChB (Hons), MD, a professor of medical cardiology and honorary consultant cardiologist at the Queen Elizabeth University Hospital, Glasgow, and colleagues wrote.1 “However, this assumption is contrary to a growing body of evidence demonstrating that certain pharmacological therapies and aerobic exercise training may reduce the risk of worsening HF events and improve symptom burden and quality of life to a greater extent in frail individuals with HF than in nonfrail HF patients.”

FINEARTS-HF was a randomized, double-blind, placebo-controlled clinical trial in patients with symptomatic HFmrEF or HFpEF, investigating the efficacy and safety of finerenone compared with matching placebo in addition to usual therapy. It enrolled 6001 patients with HF with New York Heart Association functional class II through IV, a left ventricular ejection fraction of ≥ 40%, evidence of structural heart disease, and elevated natriuretic peptide levels who were randomized in a 1:1 ratio to finerenone or matching placebo. The primary outcome was a composite of cardiovascular death and total HF events.1,2

The trial met its primary endpoint, with use of finerenone associated with a statistically significant 16% relative reduction in rate of primary outcome events compared with placebo therapy (rate ratio [RR], 0.84; 95% confidence interval [CI], 0.74-0.95; P = .007).2

To further examine the efficacy and safety of finerenone according to frailty status, investigators examined data from FINEARTS-HF for 5952 participants with a calculable frailty index (FI), which was measured using the Rockwood cumulative deficit approach. Among the cohort, the mean age was 72.0 (standard deviation [SD], 9.6) years, 54.4% of patients were male, and the mean FI was 0.284 (SD, 0.104).1

In total, 1588 (26.7%) patients had class I frailty, defined as FI ≤0.210, 2141 (36.0%) had class II frailty, defined as FI 0.211-0.310, and 2223 (37.3%) had class III frailty, defined as FI ≥0.311.1

Compared with patients with class I frailty, investigators noted those with class II and III frailty had a greater risk of the primary outcome (unadjusted RR, 1.88; 95% CI, 1.54-2.28 for class II vs RR, 3.86; 95% CI, 3.22-4.64 for class III). A similarly heightened risk was observed for each of its components and total hospitalizations.1

Of note, the effect of finerenone on the primary outcome did not vary significantly by frailty class:

• Class I RR, 1.07; 95% CI, 0.77-1.49
• Class II: RR, 0.66; 95% CI, 0.52-0.83
• Class III: RR, 0.91; 95% CI, 0.76-1.07; P for interaction = .77

Investigators additionally pointed out frailty class did not modify the effects of finerenone on the components of the primary outcome, all-cause death, or improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score. Similarly, the effects of finerenone, compared with placebo, on experiencing hypotension, elevated creatinine level, hyperkalemia, or hypokalemia did not differ by frailty class.1

“In patients with HFmrEF or HFpEF, the beneficial effects of finerenone on reducing the risk of total worsening HF events and cardiovascular death and on improving symptoms were not modified by frailty status. The effects of finerenone on experiencing hypotension, elevated creatinine level, hyperkalemia, or hypokalemia did not differ by frailty status,” investigators concluded.1 “The favorable benefit-risk balance related to frailty for finerenone should challenge any clinical reluctance to introduce this new treatment in patients considered to be frail.”

References

1. Butt JH, Jhund PS, Henderson AD, et al. Finerenone According to Frailty in Heart Failure: A Prespecified Analysis of the FINEARTS-HF Randomized Clinical Trial. JAMA Cardiol. doi:10.1001/jamacardio.2025.1775

2. Campbell P. FINEARTS-HF: Finerenone Could Find Role as Second Pillar in HFmrEF/HFpEF. HCPLive. September 1, 2024. Accessed July 9, 2025. https://www.hcplive.com/view/finearts-hf-finerenone-could-find-role-as-second-pillar-in-hfmref-hfpef