EMPEROR-Preserved Risk Model and Outcomes in the FINEARTS-HF Trial

Importance Patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or preserved EF (HFpEF) show substantial heterogeneity in prognosis. Objectives To evaluate the performance of biomarker-driven prognostic models derived from the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved) Trial in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) and to examine whether baseline risk modified the therapeutic effect of finerenone. Design, Setting, and Participants This is a prespecified secondary analysis of the FINEARTS-HF trial, which was conducted across 653 sites in 37 countries among adults aged 40 years and older with symptomatic HF and left ventricular EF (LVEF) of 40% or greater. Patients were randomized between September 2020 and January 2023, and data analysis for this study was conducted from September to October 2025. The median (IQR) follow-up period was 32 (23-37) months. Intervention Finerenone (titrated to 20 mg or 40 mg) or placebo. Main Outcomes and Measures EMPEROR-Preserved risk scores for the outcomes of first HF hospitalization or cardiovascular death, cardiovascular death, and all-cause death were calculated in FINEARTS-HF using models incorporating N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin T, New York Heart Association functional class, history of chronic obstructive pulmonary disease and diabetes, insulin use, and—depending on outcome—age, hemoglobin and albumin levels, HF duration, time from prior HF hospitalization, and sodium-glucose transporter 2 inhibitor use. Estimated risks were compared with observed event rates, and model performance was assessed using Harrell C statistic. Treatment effects were evaluated across risk quintiles (Q1 to Q5) and across the continuous risk distribution. Results Among 6001 patients (mean SD age, 72.0 9.6 years; 2732 45.5% women; 3003 randomized to finerenone and 2998 randomized to placebo), the EMPEROR-Preserved risk model estimated risk of outcomes, with Q5 vs Q1 hazard ratios (HRs) of 10.49 (95% CI, 8.14-13.52) for the composite of HF hospitalization or cardiovascular death and 13.47 (95% CI, 8.79-20.64) for cardiovascular death. The model demonstrated good discrimination. The treatment effect of finerenone was consistent across risk quintiles for first HF hospitalization or cardiovascular death (Q1: HR, 0.93 95% CI, 0.58-1.49; Q2: HR, 1.04 95% CI, 0.76-1.43; Q3: HR, 0.82 95% CI, 0.62-1.07; Q4: HR, 0.81 95% CI, 0.65-1.01; and Q5: HR, 0.88 95% CI, 0.74-1.05; P for interaction = .68) and remained uniform across the continuous risk spectrum. Conclusions and Relevance The EMPEROR-Preserved risk models demonstrated good performance in FINEARTS-HF. Baseline risk did not modify the relative treatment effect of finerenone. Trial Registration ClinicalTrials.gov Identifier: NCT04435626