TY - JOUR
T1 - Finerenone for Heart Failure and Risk Estimated by the PREDICT-HFpEF Model
T2 - A Secondary Analysis of FINEARTS-HF
AU - McDowell, Kirsty
AU - Docherty, Kieran F
AU - Campbell, Ross T
AU - Henderson, Alasdair D
AU - Jhund, Pardeep S
AU - Claggett, Brian L
AU - Desai, Akshay S
AU - Lay-Flurrie, James
AU - Hofmeister, Lucas
AU - Scalise, Andrea
AU - Lam, Carolyn S P
AU - Petrie, Mark C
AU - Schou, Morten
AU - Senni, Michele
AU - Shah, Sanjiv J
AU - Udell, Jacob A
AU - Zannad, Faiez
AU - Pitt, Bertram
AU - Vaduganathan, Muthiah
AU - Solomon, Scott D
AU - McMurray, John J V
PY - 2025/6/1
Y1 - 2025/6/1
N2 - IMPORTANCE: Patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF) have a spectrum of risk, and the effect of therapies may vary by risk.OBJECTIVES: To validate the Prognostic Models for Mortality and Morbidity in HFpEF (PREDICT-HFpEF) in the phase 3 randomized clinical trial Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) and to evaluate the effect of finerenone, compared with placebo, across the spectrum of risk in these patients.DESIGN, SETTING, AND PARTICIPANTS: The FINEARTS-HF trial was conducted across 653 sites in 37 countries. Participants were adults 40 years and older with symptomatic HF and left ventricular EF of 40% or greater randomized between September 2020 and January 2023.INTERVENTION: Finerenone (titrated to 20 mg or 40 mg) or placebo.MAIN OUTCOMES AND MEASURES: The 3 PREDICT-HFpEF risk scores for the composite outcome of cardiovascular death or HF hospitalization, cardiovascular death, and all-cause death, respectively, were calculated. Predicted risk was compared with observed outcomes. Model performance was assessed using the Harrell C statistic. The rates of the predicted outcomes (plus the composite of cardiovascular death and worsening HF events, which was the primary end point in the trial) were examined according to quintiles of risk score, as was the effect of finerenone according to risk quintiles.RESULTS: A total of 6001 patients (mean [SD] age, 72 [9.6] years; 3269 male [54.5%]) were randomized in the FINEARTS-HF trial. The C statistics for cardiovascular death or HF hospitalization, cardiovascular death, and all-cause death at 2 years were 0.71 (95% CI, 0.69-0.72), 0.68 (95% CI, 0.66-0.71), and 0.69 (95% CI, 0.67-0.71), respectively. The risk of the composite outcomes was approximately 8- to 10-fold higher in those in the highest compared with the lowest risk quintile. The relative risk reduction with finerenone compared with placebo was consistent across the spectrum of risk for all outcomes examined (eg, interaction P value for primary outcome = .24).CONCLUSIONS AND RELEVANCE: Results of the FINEARTS-HF randomized clinical trial demonstrate that the PREDICT-HFpEF models performed well in terms of calibration and discrimination. Baseline risk did not modify the benefit of finerenone.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.
AB - IMPORTANCE: Patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF) have a spectrum of risk, and the effect of therapies may vary by risk.OBJECTIVES: To validate the Prognostic Models for Mortality and Morbidity in HFpEF (PREDICT-HFpEF) in the phase 3 randomized clinical trial Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) and to evaluate the effect of finerenone, compared with placebo, across the spectrum of risk in these patients.DESIGN, SETTING, AND PARTICIPANTS: The FINEARTS-HF trial was conducted across 653 sites in 37 countries. Participants were adults 40 years and older with symptomatic HF and left ventricular EF of 40% or greater randomized between September 2020 and January 2023.INTERVENTION: Finerenone (titrated to 20 mg or 40 mg) or placebo.MAIN OUTCOMES AND MEASURES: The 3 PREDICT-HFpEF risk scores for the composite outcome of cardiovascular death or HF hospitalization, cardiovascular death, and all-cause death, respectively, were calculated. Predicted risk was compared with observed outcomes. Model performance was assessed using the Harrell C statistic. The rates of the predicted outcomes (plus the composite of cardiovascular death and worsening HF events, which was the primary end point in the trial) were examined according to quintiles of risk score, as was the effect of finerenone according to risk quintiles.RESULTS: A total of 6001 patients (mean [SD] age, 72 [9.6] years; 3269 male [54.5%]) were randomized in the FINEARTS-HF trial. The C statistics for cardiovascular death or HF hospitalization, cardiovascular death, and all-cause death at 2 years were 0.71 (95% CI, 0.69-0.72), 0.68 (95% CI, 0.66-0.71), and 0.69 (95% CI, 0.67-0.71), respectively. The risk of the composite outcomes was approximately 8- to 10-fold higher in those in the highest compared with the lowest risk quintile. The relative risk reduction with finerenone compared with placebo was consistent across the spectrum of risk for all outcomes examined (eg, interaction P value for primary outcome = .24).CONCLUSIONS AND RELEVANCE: Results of the FINEARTS-HF randomized clinical trial demonstrate that the PREDICT-HFpEF models performed well in terms of calibration and discrimination. Baseline risk did not modify the benefit of finerenone.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.
KW - Aged
KW - Female
KW - Heart Failure/drug therapy
KW - Hospitalization/statistics & numerical data
KW - Humans
KW - Male
KW - Middle Aged
KW - Mineralocorticoid Receptor Antagonists/therapeutic use
KW - Naphthyridines/therapeutic use
KW - Prognosis
KW - Risk Assessment/methods
KW - Secondary Data Analysis
KW - Stroke Volume/physiology
UR - http://www.scopus.com/inward/record.url?scp=105001537642&partnerID=8YFLogxK
U2 - 10.1001/jamacardio.2025.0025
DO - 10.1001/jamacardio.2025.0025
M3 - Journal article
C2 - 40042880
SN - 2380-6583
VL - 10
SP - 535
EP - 544
JO - JAMA Cardiology
JF - JAMA Cardiology
IS - 6
ER -