Introduction
The FINEARTS-HF trial is a pivotal, large-scale, randomized clinical study evaluating the efficacy and safety of finerenone, a non-steroidal mineralocorticoid receptor antagonist, in patients with heart failure (HF) who have mildly reduced or preserved left ventricular ejection fraction (LVEF ≥40%). Conducted across 653 sites in 37 countries, the trial enrolled 6001 symptomatic HF patients aged 40 years and older. This comprehensive summary categorizes and reviews key findings from multiple prespecified analyses of the trial to provide a detailed understanding of finerenone’s role in treating this patient population.
1. Efficacy and Safety in Women and Men
An analysis stratified by sex showed that finerenone effectively reduced the composite primary end point—cardiovascular death and total (first and recurrent) HF events—similarly in women and men. Women comprised 45.5% of the cohort and exhibited distinct baseline characteristics such as older age, higher LVEF, and worse symptom burden. Nonetheless, finerenone lowered risk consistently (rate ratio 0.78 for women and 0.88 for men; interaction P=0.41). Health status, measured by Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS), improved significantly independent of sex, with comparable tolerability.
2. Effectiveness Across Ejection Fraction Spectrum
Prespecified analyses examined finerenone’s efficacy across LVEF categories: <50%, 50% to <60%, and ≥60%. The therapy reduced cardiovascular death and HF event risk across these ranges without significant interaction, indicating robust benefits even at higher LVEF values. Patients with higher LVEF tended to be older, more often female, and had more hypertension and chronic kidney disease but less coronary artery disease. Finerenone’s consistent reduction in worsening HF events irrespective of LVEF reinforces its broad applicability to HF patients with preserved or mildly reduced EF.
3. Benefits in Patients with Recent Worsening Heart Failure (WHF) Events
Patients recently hospitalized or treated urgently for HF (within 7 days to 3 months) represented a high-risk subgroup. Their rates of cardiovascular death and HF events were more than double those without recent WHF. Finerenone demonstrated a greater absolute reduction in these events among those with recent WHF, particularly within 7 days and up to 3 months of the event. Although the treatment-by-time interaction was not definitive, these findings suggest enhanced benefits when finerenone is initiated timely after an HF exacerbation, without increasing adverse events such as hyperkalemia or worsening renal function.
4. Kidney Outcomes with Finerenone
Kidney function, assessed by estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR), was impacted favorably. While an acute initial eGFR decline occurred over the first 3 months of treatment (-2.9 mL/min/1.73 m2), finerenone did not adversely affect the long-term eGFR slope compared with placebo. Finerenone significantly reduced albuminuria by 30% at 6 months and lowered the risk of new-onset microalbuminuria and macroalbuminuria by 24% and 38%, respectively. However, no significant differences emerged in composite kidney outcomes such as ≥50% eGFR decline or kidney failure, likely reflecting the relatively low baseline risk in this population.
5. Impact on Health Status and Symptom Burden
Finerenone improved patient-reported health status measured via KCCQ-TSS. Baseline KCCQ-TSS was a strong predictor of risk, with worse scores indicating higher HF event incidence. Across all tertiles of baseline scores, finerenone reduced primary endpoint risk consistently (interaction P=0.89) and yielded a significant mean improvement of 1.62 points at 12 months compared to placebo. Additionally, fewer patients experienced clinical deterioration, and more experienced symptomatic improvement under finerenone therapy.
6. Effect on New-Onset Diabetes
Among the 53.7% of participants without diabetes at baseline, finerenone significantly reduced the risk of developing new-onset diabetes by 24% compared with placebo (hazard ratio 0.76; P=0.026). This effect was confirmed using competing risk analyses, across diverse sensitivity checks including expanded definitions of diabetes onset, and was consistent across patient subgroups. This finding represents an important additional clinical benefit of finerenone in HF patients beyond cardiovascular protection.
7. Influence of Frailty on Treatment Outcomes
Frailty status, assessed using a frailty index (FI), classified patients into three groups: not frail (FI ≤0.210), more frail (FI 0.211-0.310), and most frail (FI ≥0.311). Frailty was associated with markedly higher risk of cardiovascular death and worsening HF events. Finerenone reduced these risks regardless of frailty class without significant interaction effects (P=0.77). Similarly, its effects on all-cause mortality, symptoms, and adverse events including hypotension and hyperkalemia did not vary by frailty level, supporting finerenone’s safety and efficacy across a spectrum of patient vulnerability.
Discussion and Clinical Implications
The FINEARTS-HF trial highlights finerenone as an effective and well-tolerated therapeutic option for symptomatic HF patients with mildly reduced or preserved ejection fraction. Its benefits span diverse subpopulations including women, men, patients with higher or lower LVEF, those recently hospitalized for HF, and patients with varying degrees of frailty. Finerenone not only reduces cardiovascular death and HF hospitalizations but also improves quality of life and may prevent the development of diabetes, which is common and impactful in this population.
While kidney composite endpoints were not significantly modified, the consistent albuminuria reduction suggests renoprotective effects worthy of further exploration. The initial eGFR decline should be anticipated but does not translate to worsening long-term renal function, aligning with mechanisms of optimized mineralocorticoid receptor antagonism.
Clinicians should consider finerenone as part of comprehensive HF management, particularly benefitting those at increased risk post-worsening events, regardless of sex or frailty status. The drug’s safety profile and symptom benefits also support its use across a broad clinical spectrum.
Conclusion
In summary, the FINEARTS-HF trial establishes finerenone as a valuable treatment for heart failure with mildly reduced or preserved ejection fraction, demonstrating consistent reductions in cardiovascular death and heart failure events, symptom improvement, lowered new-onset diabetes risk, and favorable kidney effects. These findings foster confidence in finerenone’s role as an integral component of contemporary HF care for diverse patient groups.
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