{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T21:57:58Z","timestamp":1793656678903,"version":"4.5.1"},"reference-count":10,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:sec><jats:title>Importance<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the clinical profiles, risk, and treatment response to finerenone in participants with HFimpEF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Intervention<\/jats:title><jats:p>Participants received finerenone (titrated to 20 mg or 40 mg) or placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary end point was the composite of cardiovascular (CV) death and total (first and recurrent) worsening HF events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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, <jats:italic>P<\/jats:italic>\u2009=\u2009.39). 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 (<jats:italic>P<\/jats:italic> for interaction\u2009=\u2009.36). 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%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04435626?cond=NCT04435626&amp;amp;amp;rank=1\">NCT04435626<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamacardio.2025.1101","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T11:31:01Z","timestamp":1747827061000},"page":"740","source":"Crossref","is-referenced-by-count":26,"title":["Finerenone in Heart Failure With Improved Ejection Fraction"],"prefix":"10.1001","volume":"10","author":[{"given":"Maria A.","family":"Pabon","sequence":"first","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orly","family":"Vardeny","sequence":"additional","affiliation":[{"name":"Minneapolis VA Center for Care Delivery and Outcomes Research, University of Minnesota, Minneapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muthiah","family":"Vaduganathan","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay S.","family":"Desai","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian J.","family":"Kulac","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pardeep S.","family":"Jhund","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn S. P.","family":"Lam","sequence":"additional","affiliation":[{"name":"National Heart Centre Singapore and Duke-National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Senni","sequence":"additional","affiliation":[{"name":"University Bicocca Milan, Milan, Italy"},{"name":"Papa Giovanni XXIII Hospital, Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjiv J.","family":"Shah","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm Clinical Investigation Centre, CHU, Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara I.","family":"Saldarriaga","sequence":"additional","affiliation":[{"name":"Centro Cardiovascular Colombiano, Cl\u00ednica Santa Mar\u00eda, Medell\u00edn, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Petrie","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9la","family":"Merkely","sequence":"additional","affiliation":[{"name":"Heart and Vascular Centre, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Borentain","sequence":"additional","affiliation":[{"name":"Pharmaceuticals, Research & Development, Bayer, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Mueller","sequence":"additional","affiliation":[{"name":"Pharmaceuticals, Research & Development, Bayer, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhakar","family":"Viswanathan","sequence":"additional","affiliation":[{"name":"Pharmaceuticals, Research & Development, Bayer, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flaviana","family":"Amarante","sequence":"additional","affiliation":[{"name":"Pharmaceuticals, Research & Development, Bayer, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alanna","family":"Morris","sequence":"additional","affiliation":[{"name":"Pharmaceuticals, Research & Development, Bayer, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J. 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