FINEARTS-HF: Finerenone Benefit Remains Consistent Across Frailty Classes in Heart Failure

A prespecified analysis of the phase 3 FINEARTS-HF trial found that finerenone significantly reduced the risk of cardiovascular death and worsening heart failure (HF) events in patients with mildly reduced or preserved ejection fraction, regardless of frailty status. The findings, which were published in JAMA Cardiology, challenge assumptions that patients classified as frail may not tolerate or benefit from novel therapies.

“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,” explained the study authors. “Thus, clinicians may be more reluctant to initiate new therapies in these individuals due to anticipation of a less favorable benefit-risk profile in patients with frailty.”

In the multicenter, placebo-controlled, double-blind, randomized phase 3 clinical trial, FINEARTS-HF (ClinicalTrials.gov ID: NCT04435626), investigators are evaluating the efficacy and safety of finerenone in patients with HF and mildly reduced ejection fraction (HFmrEF) or with HF and preserved ejection fraction (HFpEF). The new publication presents results of a prespecified secondary analysis.

The study enrolled patients aged 40 years and older who had HF with New York Heart Association functional class II through IV, a left ventricular ejection fraction of  40% or higher, evidence of structural heart disease, and elevated natriuretic peptide levels. Between September 2020 and January 2023, they were randomized (1:1) to receive once-daily finerenone or placebo in addition to usual therapy.

The primary outcome was a composite of cardiovascular death and total (first and recurrent) HF events, defined as HF hospitalization or urgent HF visit. The investigators measured frailty using the Rockwood cumulative deficit approach.

Among 6,001 patients randomized in the study, the frailty index (FI) could be calculated for 5,952 patients (mean age, 72.0 years; male, 54.4%). Of those, 26.7% had class I frailty (FI ≤0.210, considered not frail); 36.0% had class II frailty (FI 0.211-0.310, considered more frail); and 37.3% had class III frailty (FI ≥0.311, considered most frail).

The investigators found that patients with class II and III frailty had a greater risk of the composite primary outcome compared with patients with class I frailty (unadjusted rate ratio [RR] for class II, 1.88; 95% CI, 1.54-2.28; RR for class III, 3.86; 95% CI, 3.22-4.64); however, they found that the effect of finerenone on the primary outcome did not vary significantly by frailty class (RR for class I, 1.07; 95% CI, 0.77-1.49; RR for class II, 0.66; 95% CI, 0.52-0.83; RR for class III, 0.91; 95% CI, 0.76-1.07; P for interaction = 0.77).

The study also revealed that 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 did not differ by frailty class. Similarly, the effects of finerenone on patients experiencing hypotension, elevated creatinine level, hyperkalemia, or hypokalemia did not differ by frailty class.

“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,” concluded the authors. “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.”

Limitations of the study included possible exclusion of the most frail patients with HF, lack of muscle strength and functional capacity data, differing patient monitoring on trial versus in clinical practice, and possibility of unmeasured confounding factors.

Disclosure(s):

Disclosure: This research was supported by Bayer AG. Please see the original reference for a full list of disclosures.