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Randomized Controlled Trial
. 2025 Jul 1;10(7):740-745.
doi: 10.1001/jamacardio.2025.1101.

Finerenone in Heart Failure With Improved Ejection Fraction: The FINEARTS-HF Randomized Clinical Trial

Maria A Pabon  1 , Orly Vardeny  2 , Muthiah Vaduganathan  1 , Akshay S Desai  1 , Brian L Claggett  1 , Ian J Kulac  1 , Pardeep S Jhund  3 , Carolyn S P Lam  4 , Michele Senni  5   6 , Sanjiv J Shah  7 , Adriaan A Voors  8 , Faiez Zannad  9 , Bertram Pitt  10 , Clara I Saldarriaga  11 , Mark C Petrie  12 , Béla Merkely  13 , Maria Borentain  14 , Katharina Mueller  14 , Prabhakar Viswanathan  14 , Flaviana Amarante  14 , Alanna Morris  14 , John J V McMurray  3 , Scott D Solomon  1
Affiliations
Randomized Controlled Trial

Finerenone in Heart Failure With Improved Ejection Fraction: The FINEARTS-HF Randomized Clinical Trial

Maria A Pabon et al. JAMA Cardiol. .

Abstract

Importance: Patients with chronic heart failure (HF) and left ventricular ejection fraction (LVEF) less than 40% who experience LVEF improvement to 40% or higher (HFimpEF) may still face residual risks.

Objective: To assess the clinical profiles, risk, and treatment response to finerenone in participants with HFimpEF.

Design, setting, and participants: A total of 6001 patients with HE, LVEF of 40% or higher, New York Heart Association class II to IV symptoms, and elevated natriuretic peptide levels, were enrolled between September 14, 2020, and January 10, 2023. Patients with a prior history of LVEF less than 40% were included. Data analysis was conducted between September 1 to December 10, 2024.

Intervention: Participants received finerenone (titrated to 20 mg or 40 mg) or placebo.

Main outcomes and measures: The primary end point was the composite of cardiovascular (CV) death and total (first and recurrent) worsening HF events.

Results: Of the 6001 participants (mean [SD] age, 72 [9.7], years; 3269 male [55%]), 273 (5%) had a prior LVEF less than 40%. Among those with a prior LVEF of less than 40%, the median recorded prior LVEF was 35% [IQR, 30%-37%], with a median improvement of 12% [IQR, 8%-17%]. Over a median follow-up of 2.6 years, those with a history of LVEF of less than 40% experienced higher rates of the primary outcome of a composite of CV death and worsening of HF events (21.4 per 100 patient-years vs 16.0 per 100 patient-years) than did those whose LVEF was consistently 40% or higher. After adjustment for clinically relevant covariates; however, this rate ratio (RR) was not statistically different (absolute RR, 1.13; 95% CI, 0.85-1.49, P = .39). The treatment effect of finerenone on the primary outcome was consistent among those with a history of LVEF less than 40% and those with LVEF that was consistently 40% or higher (P for interaction = .36). Owing to higher baseline risk, the absolute risk reduction was greater among those with HFimpEF (9.2 vs 2.5 per 100 patient-years). Patients with HFimpEF tended to develop more hypotension with finerenone treatment, but otherwise, the safety profile of finerenone was similar in patients with and without previous LVEF less than 40%.

Conclusions and relevance: In this prespecified analysis of a randomized clinical trial, patients with HFimpEF remained at high risk of CV events, underscoring the need for continued management despite LVEF improvement. The treatment benefits of finerenone observed among the overall population of patients with HF with preserved EF were consistent among patients with HFimpEF.

Trial registration: ClinicalTrials.gov Identifier: NCT04435626.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Vardeny reported receiving grants from AstraZeneca, and Bayer; research support to her institution from Cardurion Research; and consulting fees from Cardior, Moderna, and Cytokinetics outside the submitted work. Dr Vaduganathan reported receiving consulting fees from American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Bristol Myers Squibb, 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; research grant support, served on advisory boards, or had speaker engagements and grants from Amgen, AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics clinical trial committees outside the submitted work. Dr Desai reported receiving grants from Bayer, an institutional research grant to Brigham Women’s Hospital to support clinical end points committee activities; and consulting fees from Bayer during the conduct of the study; institutional grants from Abbott, Alnylam, AstraZeneca, and Novartis; and consulting fees from Avidity Biopharma, Axon Therapeutics, Biofourmis, Boston Scientific, Endotronix, GlaxoSmithKline, Merck, Medpace, Icon Clinical Research, Medtronic, New Amsterdam, Novartis, Abbott, Alnylam, AstraZeneca, Parexel, Regeneron, Roche, River2Renal, scPharmaceuticals, Veristat, Verily, and Zydus outside the submitted work. Dr Claggett reported receiving statistical consulting fees from Alnylam Statistical, Cardior, Cytokinetics, CVRx, Intellia, Rocket, and Eli Lilly outside the submitted work. Dr Jhund reported receiving research support to his institution from Bayer AG, during the conduct of the study; research support from AstraZeneca, speaker and advisory board fees and research support to his institution from NovoNordisk, and grants from AstraZeneca, Analog Devices Inc, ProAdWise Communications, and Roche Diagnostics outside the submitted work; and serving as the director of GCTP Ltd. Dr Lam reported receiving grants from the National Medical Research Council of Singapore; being supported by a clinician-scientist award from the National Medical Research Council of Singapore; research support from NovoNordisk, and Roche Diagnostics; serving as a consultant for, on the advisory board or steering or executive committees of Alnylam Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Corteria, and CPC Clinical, Research, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Quidel, Radcliffe Group Ltd, and Roche; and cofounding and serving as the Us2.ai Serves nonexecutive director outside the submitted work; and having a patent pending (PCT/SG2016/050217) and a patent issued (US10,702,247). Dr Senni reported receiving personal fees from Novartis, Bayer, Merck, MSD, Abbott, VIFOR, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Cardurion outside the submitted work. Dr Shah reported receiving consulting fees from Bayer during the conduct of the study. Dr Voors reported receiving consulting fees from Merck and Bayer to his institution outside the submitted work. Dr Pitt reported receiving consulting fees from Bayer, AstraZeneca, Boehringer Ingelheim, Anacardio, SQ Innovations, G3 Pharmaceuticals, KBP Biosciences, Cereno Scientific, Sarfez Pharmaceuticals, Prointel, Sea Star, BrainStorm, and Lexicon outside the submitted work; having stock options for SC Pharmaceuticals, SQ Innovations, G3 Pharmaceuticals, KBP Biosciences, KBP Biosciences, Cereno Scientific, Sarfez Pharmaceuticals, Prointel, Sea Star, and BrainStorm; having a patent pending (US63/045,783) and patent issued (US 9931412). Dr Saldarriaga reported receiving speaker and consulting fees from Bayer, Merck, Novartis, AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Servier, Pfizer, Sanofi, Bristol Myers Squibb outside the submitted work. Dr Petrie reported receiving research funding from Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, and Pharmacosmos and serving as a consultant to Abbott, Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Corteria, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Horizon Therapeutics, Foundry, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, 3R Lifesciences, Reprieve, FIRE 1, Corvia, and Regeneron. Dr Merkely reported receiving support from AstraZeneca, Boehringer Ingelheim, Biotronik, Medtronic, and Novartis outside the submitted work. Dr Borentain reported being an employee of Bayer. Dr Viswanathan reported being a full-time employee of Bayer. Dr Amarante reported being a full-time employee of Bayer during the conduct of the study. Dr Morris reported receiving personal fees prior to current employment at Bayer from Abbott, Boehringer Ingelheim and Lilly, Cytokinetics, Merck, Novo Nordisk, and Regeneron outside the submitted work. Dr McMurray reported receiving speaker fees from Abbott, Alkem Metabolics, AstraZeneca, 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, JB Chemicals & Pharmaceuticals Ltd, Lupin Pharmaceuticals, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, and Translational Medicine Academy; consulting fees from Alynylam Pharmaceuticals, Amgen, AnaCardio, AstraZeneca, Bayer, Berlin Cures, Bristol Myers Squibb, Cardurion, Cytokinetics, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, and River 2 Renal Corp; and support paid to his institution from Novartis, Cytokinetics, GSK, Astra Zeneca, and Cardurion; personal fees for serving as the director of Global Clinical Trial Partners Ltd; other support to his institution from the British Heart Foundation, the NHLBI, Boehringer Ingelheim, SQ Innovations, Catalyze Group; and serving on the data and safety monitoring board of the WIRB-Copernicus Group Clinical Inc outside the submitted work. Dr Solomon reported receiving grants to his institution from Alexion, Alnylam, Applied Therapeutics, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Boston Scientific, Cytokinetics, Edgewise, Eidos/BridgeBio, Gossamer, GSK, Ionis, Lilly, the NHLBI, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Tenaya, Theracos, and US2.AI and consulting fees from Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Bristol Myers Squibb, 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, and Valo outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Kaplan-Meier Curve for Total Heart Failure Events and Cardiovascular Death
LVEF indicates left ventricular ejection fraction; RR, risk reduction; ARR, absolute risk reduction.
See this image and copyright information in PMC

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