Finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), has demonstrated the potential to extend event-free survival by up to three years in patients with heart failure (HF) with mildly reduced or preserved ejection fraction (HFmrEF or HFpEF). This finding comes from a prespecified analysis of the Finerenone Trial to Investigate the Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF), a phase 3 randomized clinical trial. The results, published in JAMA Cardiology, suggest that finerenone could significantly improve long-term outcomes for this patient population.
The FINEARTS-HF trial involved 6001 participants across 653 sites in 37 countries. Participants, aged 40 years and older with symptomatic HF and a left ventricular ejection fraction of 40% or greater, were randomized to receive either finerenone (titrated to 20 mg or 40 mg) or placebo. The primary outcome measured was the time to cardiovascular death or a worsening HF event. The median follow-up was 2.6 years.
Event-Free Survival Gains
The analysis estimated long-term gains in survival free from the primary endpoint using age-based Kaplan-Meier curves. For a 55-year-old participant, the mean survival free from cardiovascular death or a worsening HF event was 13.6 years with finerenone compared to 10.5 years with placebo, a gain of 3.1 years (95% CI, 0.8-5.4 years; P = .007). For a 65-year-old, the gain was 2.0 years (95% CI, 0.8-3.3 years; P = .001), with mean event-free survival of 11.0 years and 8.9 years, respectively.
Benefits Regardless of SGLT2 Inhibitor Use
Notably, the benefits of finerenone were observed even in individuals already treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor. Among those taking an SGLT2 inhibitor at baseline, a 65-year-old participant could expect a 3.1-year gain in event-free survival (95% CI, 0.1-6.0 years; P = .04). For those not on an SGLT2 inhibitor, the gain was 1.8 years (95% CI, 0.5-3.1 years; P = .009).
Clinical Implications
These findings suggest that finerenone can play a significant role in modifying the longitudinal risks of clinical events in HFmrEF and HFpEF patients. According to the researchers, the estimated long-term therapeutic benefits can be useful to aid clinical decision-making. Scott D. Solomon, MD, Brigham and Women’s Hospital, Harvard Medical School, and corresponding author of the study, noted that the drug represents a new class that may become a pillar of therapy for this disease.
Addressing Unmet Needs in Heart Failure
Patients with HFmrEF or HFpEF have substantially curtailed life expectancy free from clinical events. Until recently, management focused on short-term symptom control. SGLT2 inhibitors were the first evidence-based therapies to reduce cardiovascular events in this population. Finerenone now offers another option to reduce the risks of cardiovascular death and worsening HF events.
Study Design and Limitations
The FINEARTS-HF trial was a global, event-driven, placebo-controlled, randomized clinical trial. Key inclusion criteria included age of 40 years or older, New York Heart Association functional class II or greater symptoms, elevated natriuretic peptide levels, and evidence of structural heart disease. Participants were randomized 1:1 to finerenone or placebo. The primary endpoint was cardiovascular death and total worsening HF events.
The study's limitations include the assumption that treatment effects observed during the trial will persist for the patient's lifetime. Interval nonadherence, temporary interruption, or premature discontinuation may attenuate these projections. Additionally, the trial excluded individuals with life-threatening cardiovascular or noncardiovascular illness, which may limit the generalizability of the findings.
Finerenone: A Promising Therapy
Overall, the FINEARTS-HF trial and this prespecified analysis provide compelling evidence for the long-term benefits of finerenone in patients with heart failure with mildly reduced or preserved ejection fraction. The findings support the use of finerenone to extend event-free survival and improve outcomes in this challenging patient population.
