The FINO-HF trial: a randomised comparison of finerenone versus spironolactone in patients with heart failure with reduced ejection fraction - biomarker and clinical outcomes
R Rascon Sabido, Y G J Yoloxochilt Garcia Jimenez, S M R Sadoc Marin Rendon, J I S G Juan Ignacio Soto Gonzalez, G M C Gustavo Moreno Castillo, F Z O Fabiola Zarate Ordonez, M U L Marcelo Utrera Lagunas, V B D Victor Bernal Dolores, A C M Adolfo Chavez Mendoza, L F A M Luisa Fernanda Aguilera Mora, C G S Carlos Guizar Sanchez, S C H L Sergio Chavez LealAbstract
Background
Mineralocorticoid receptor antagonists (MRAs) reduce morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). However, steroidal MRAs like spironolactone are associated with hormone-related adverse effects and higher rates of hyperkalaemia. Finerenone, a novel non-steroidal MRA, offers greater receptor selectivity and a potentially safer profile. Direct head-to-head comparisons with spironolactone in real-world HFrEF populations, including biomarker sub-studies, are lacking.
Purpose
To compare the efficacy, biomarker response, and safety of finerenone versus spironolactone in patients with HFrEF over 3 months of follow-up.
Methods
This single-centre, randomised, open-label trial enrolled 500 patients with chronic HFrEF (LVEF ≤40%), NYHA class II-III, on stable guideline-directed medical therapy (including ACEi/ARB/ARNI and beta-blockers). Patients were randomised 2:1 to receive either spironolactone (uptitrated to 25 mg or 50 mg daily; n=334) or finerenone (uptitrated to 20 mg or 40 mg daily; n=166). The primary endpoint was the composite of heart failure hospitalisation or cardiovascular death at 3 months. Key secondary endpoints included change in NT-proBNP from baseline to 3 months, incidence of hyperkalaemia (>5.5 mmol/L), worsening renal function, and gynaecomastia. Analysis was by intention-to-treat.
Results
Baseline characteristics were well-balanced (mean age 68 years, 74% male, mean LVEF 33%, mean NT-proBNP 1850 pg/mL). At 3 months, the primary composite endpoint occurred in 44 patients (13.2%) in the spironolactone group versus 14 patients (8.4%) in the finerenone group (HR: 0.64; 95% CI 0.43–0.95; p=0.03). Heart failure hospitalisation was significantly reduced with finerenone (6.0% vs. 10.2%; p=0.02). Cardiovascular mortality was lower with finerenone (2.4% vs. 4.5%; HR: 0.53; 95% CI 0.28–0.99; p=0.048). NT-proBNP reduction was significantly greater with finerenone: median change -43% (IQR -59 to -25) vs. -31% (IQR -47 to -16); p=0.004. Hyperkalaemia (>5.5 mmol/L) occurred in 7.2% of finerenone patients versus 14.1% of spironolactone patients (p=0.005), worsening renal function (>30% eGFR decline) in 5.4% vs. 9.6% (p=0.04), and gynaecomastia in 0.6% vs. 8.1% (p<0.001). Discontinuation due to adverse events was lower with finerenone (3.6% vs. 8.7%; p=0.01).
Conclusion
In patients with HFrEF, finerenone significantly reduced the composite of heart failure hospitalisation and cardiovascular death at 3 months compared with spironolactone, with greater NT-proBNP reduction and a significantly better safety profile. These findings support finerenone as a preferred MRA in HFrEF management