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Clinical Trial
. 2025 Jun 1;10(6):535-544.
doi: 10.1001/jamacardio.2025.0025.

Finerenone for Heart Failure and Risk Estimated by the PREDICT-HFpEF Model: A Secondary Analysis of FINEARTS-HF

Kirsty McDowell  1 , Kieran F Docherty  1 , Ross T Campbell  1 , Alasdair D Henderson  1 , Pardeep S Jhund  1 , Brian L Claggett  2 , Akshay S Desai  2 , James Lay-Flurrie  3 , Lucas Hofmeister  4 , Andrea Scalise  5 , Carolyn S P Lam  6 , Mark C Petrie  1 , Morten Schou  7 , Michele Senni  8 , Sanjiv J Shah  9 , Jacob A Udell  10 , Faiez Zannad  11 , Bertram Pitt  12 , Muthiah Vaduganathan  2 , Scott D Solomon  2 , John J V McMurray  1
Affiliations
Clinical Trial

Finerenone for Heart Failure and Risk Estimated by the PREDICT-HFpEF Model: A Secondary Analysis of FINEARTS-HF

Kirsty McDowell et al. JAMA Cardiol. .

Erratum in

  • Error in Figure 3.
    [No authors listed] [No authors listed] JAMA Cardiol. 2025 Jun 1;10(6):635. doi: 10.1001/jamacardio.2025.1107. JAMA Cardiol. 2025. PMID: 40238143 Free PMC article. No abstract available.

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Docherty reported sitting on a clinical event adjudication for Bayer, being employed by AstraZeneca, receiving grants paid to institution from Boehringer Ingelheim and Roche, and advisory board fees, speaker fees, trial committee fees and/or equity from Abbott, FIRE-1, US2.AI, AstraZeneca, and Boehringer Ingelheim outside the submitted work. Dr Campbell reported receiving speaker/consultant fees from AstraZeneca and Bayer outside the submitted work. Dr Henderson reported receiving personal fees from Bayer outside the submitted work. Dr Jhund reported receiving trial remuneration from Bayer, Novartis, AstraZeneca, and Novo Nordisk; grants from AstraZeneca, Boehringer Ingelheim, Analog Devices, and Roche Diagnostics; personal fees from ProAdwise; and serving as director for GCTP Ltd. Dr Claggett reported receiving consulting fees from Alnylam, Cardior, Cardurion, Cytokinetics, CVRx, Intellia, Rocket, and Eli Lilly outside the submitted work. Dr Desai reported receiving grants and consulting fees from Bayer; grants from Abbott, Alnylam, AstraZeneca, Novartis, DevPro Biopharma, and Pfizer; and personal/consulting fees from Abbott, Alnylam, AstraZeneca, Avidity Biopharma, Axon Therapeutics, Biofourmis, Boston Scientific, Endotronix, iRhythm, GlaxoSmithKline, Merck, Medpace, Medtronic, New Amsterdam, Novartis, Parexel, Regeneron, River2Renal, Roche, scPharmaceuticals, Veristat, Verily, and Zydus outside the submitted work. Dr Lay-Flurrie reported being a full-time employee of and receiving personal fees from Bayer during the conduct of the study. Dr Hofmeister reported being an employee of Bayer AG. Dr Lam reported receiving grants from National Medical Research Council of Singapore C.S.L, a clinician scientist award from the National Medical Research Council of Singapore, research support from Novo Nordisk and Roche; consultant/advisory board/committee fees from Alnylam Pharma, AnaCardio AB, AstraZeneca, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Corteria, CPC Clinical Research, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Quidel Corporation, Radcliffe Group Ltd, and Roche; and cofounder/nonexecutive director of US2.AI outside the submitted work; in addition, Dr Lam reported having a patent for PCT/SG2016/050217 pending for diagnosis and prognosis of chronic heart failure and a patent for automated clinical workflow that recognizes and analyses 2-dimensional and Doppler echo images for cardiac measurements and the diagnosis, prediction, and prognosis of heart disease. Dr Petrie reported receiving grants and personal fees from Boehringer Ingelheim, Astra Zeneca, Novartis, Novo Nordisk, Roche, and SQ Innovations and personal fees from Foundry, Corteria, Pharmacosmos, Amgen, AbbVie, Bayer, Horizon, Regeneron, Eli Lilly, Reprieve, AnaCardio, New Amsterdam, Teikoku, Corvia, Moderna, Biosensors, and LIB Therapeutics outside the submitted work. Dr Schou reported receiving lecture fees from Boehringer Ingelheim, Novo Nordisk, Novartis, AstraZeneca and grants from ESC Congress 2024 Congress Grant to ESC Bayer outside the submitted work. Dr Senni reported receiving personal fees from Novartis, Bayer, Merck, MSD, Vifor, Abbott, Boehringer Ingelheim, Novo Nordisk, AstraZeneca, and Cardurion outside the submitted work. Dr Shah reported receiving consulting fees from Bayer during the conduct of the study. Dr Udell reported receiving personal fees from Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Novavax, Sanofi, and Boehringer Ingelheim and grants from Bayer and Boehringer Ingelheim outside the submitted work. Dr Zannad reported receiving committee fees from Bayer; personal fees from 89bio, Applied Therapeutics, Bayer, Betagenon, Biopeutics, Boehringer Ingelheim, Cambrian, Cardior, Cellprothera, Cereno Pharmaceutical, Corteria, CVRx, Lupin, Merck, Northsea, Otsuka, Owkin, Ribocure, Salubris, and Viatris; having stock options or equities at Cereno Pharmaceutical; and being the founder of Cardiovascular Clinical Trialists. Dr Pitt reported receiving consultant fees and/or stock options from Bayer, Boehringer Ingelheim, Lexicon, Vifor, Anacardio, SQinnovations, SC Pharmaceuticals, Sarfez Pharmaceuticals, KBP Biosciences, Cereno, Sea Staqr, and Prointel; in addition, Dr Pitt reported having a patent issued for site-specific delivery of epelerenone to the myocardium and a patent pending for histone-modulating agents for the protection and treatment of organ damage. Dr Vaduganathan reported receiving research grant support, serving on advisory boards, or having speaker engagements from American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health and serving on clinical trial committees for Amgen, AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics outside the submitted work. Dr Solomon reported receiving grants from Bayer, Alexion, Alnylam, Applied Therapeutics, AstraZeneca, Bellerophon, Bayer, BMS, Boston Scientific, Cytokinetics, Edgewise, Eidos/BridgeBio, Gossamer, GSK, Ionis, Lilly, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Tenaya, Theracos, and US2.AI and consulting fees from Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, BMS, Cardior, Cardurion, Corvia, Cytokinetics, GSK, Intellia, Lilly, Novartis, Roche, Theracos, Quantum Genomics, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, Valo outside the submitted work. Dr McMurray reported receiving payment from Bayer to Glasgow University during the conduct of the study; lecture fees from Abbott, Alkem Metabolics, Astra Zeneca, Blue Ocean Scientific Solutions Ltd., Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals Ltd., Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J.B. Chemicals & Pharmaceuticals Ltd, Lupin Pharmaceuticals, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, Translational Medicine Academy; consultant fees from Alynylam Pharmaceuticals, Amgen, AnaCardio, AstraZeneca, Bayer, Berlin Cures, BMS, Cardurion, Cytokinetics, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, River 2 Renal Corp; support for clinical trial from Novartis, Cytokinetics, Amgen, GSK, Cardurion, AstraZeneca payment to Glasgow University; serving as director of Global Clinical Trial Partners Ltd; research funding from British Heart Foundation, National Institute for Health/National Heart, Lung, and Blood Institute, Boehringer Ingelheim, SQ Innovations, Catalyze Group payment to Glasgow University, and data safety monitoring board fees from WIRB-Copernicus Group Clinical Inc outside the submitted work. No other disclosures were reported.

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