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EMPACT-MI (Study to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) was a double-blind, multicenter clinical trial that randomized 6,522 patients with acute myocardial infarction and risk for heart failure to empagliflozin or placebo. Here we show in this secondary analysis that the mean estimated glomerular filtration rate at baseline was 76.1\u2009ml\u2009min<jats:sup>\u22121<\/jats:sup>\u20091.73\u2009m<jats:sup>\u2212<\/jats:sup>\n            <jats:sup>2<\/jats:sup> (s.d.\u2009=\u200919.9\u2009ml\u2009min<jats:sup>\u22121<\/jats:sup>\u20091.73\u2009m<jats:sup>\u2212<\/jats:sup>\n            <jats:sup>2<\/jats:sup>), with longitudinal kidney function data available for 1,152 (17.7%) treated patients from select countries. By 24 months, compared with baseline, the estimated glomerular filtration rate was similar in the empagliflozin group but declined in the placebo group (<jats:italic>P<\/jats:italic>\u2009=\u20090.01). Empagliflozin reduced the total adverse events of heart failure or all-cause mortality irrespective of kidney function (<jats:italic>P<\/jats:italic>\n            <jats:sub>interaction<\/jats:sub>\u2009=\u20090.30). Thirty-day adverse event rates were similar by treatment group and consistent across baseline kidney function. Empagliflozin had kidney-protective effects, reduced heart failure outcomes and was safe to initiate soon after acute myocardial infarction across baseline kidney function.<\/jats:p>","DOI":"10.1038\/s44161-025-00657-7","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T09:02:55Z","timestamp":1749805375000},"page":"761-772","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Secondary analysis of the EMPACT-MI trial reveals cardiovascular\u2013kidney efficacy and safety of empagliflozin after acute myocardial infarction"],"prefix":"10.1038","volume":"4","author":[{"given":"Rahul","family":"Aggarwal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-6245","authenticated-orcid":false,"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian F.","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0805-8683","authenticated-orcid":false,"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Harrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Schuyler","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Mattheus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6333-9496","authenticated-orcid":false,"given":"Mark C.","family":"Petrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Steubl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3827-5793","authenticated-orcid":false,"given":"Mikhail","family":"Sumin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram","family":"Thanam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob A.","family":"Udell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7683-4720","authenticated-orcid":false,"given":"Javed","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"657_CR1","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1056\/NEJMoa2314051","volume":"390","author":"J Butler","year":"2024","unstructured":"Butler, J. et al. Empagliflozin after acute myocardial infarction. N. Engl. J. Med. 390, 1455\u20131466 (2024).","journal-title":"N. Engl. J. Med."},{"key":"657_CR2","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1161\/CIRCULATIONAHA.124.069217","volume":"149","author":"AF Hernandez","year":"2024","unstructured":"Hernandez, A. F. et al. Effect of empagliflozin on heart failure outcomes after acute myocardial infarction: insights from the EMPACT-MI trial. Circulation 149, 1627\u20131638 (2024).","journal-title":"Circulation"},{"key":"657_CR3","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.ahj.2022.05.010","volume":"253","author":"J Harrington","year":"2022","unstructured":"Harrington, J. et al. Empagliflozin in patients post myocardial infarction rationale and design of the EMPACT-MI trial. Am. Heart J. 253, 86\u201398 (2022).","journal-title":"Am. 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D.L.B. discloses the following relationships: advisory board membership for Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, E-Star Biotech, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, NirvaMed, Novo Nordisk, Stasys and Tourmaline Bio; board of directors membership and stock holding for the American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options) and High Enroll (stock). He has been a consultant for Broadview Ventures, Corcept Therapeutics, GlaxoSmithKline, Hims, SFJ, Summa Therapeutics and Youngene. He reports membership of the following data monitoring committees: Acesion Pharma, Assistance Publique-H\u00f4pitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; and Rutgers University (for the National Institutes of Health (NIH)-funded MINT Trial). He reports honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi\/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), the Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor and Associate Editor), Level Ex, Medtelligence\/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee), and Clinical Cardiology (Deputy Editor). He is named on a patent application (17\/574,977) for sotagliflozin assigned to Brigham and Women\u2019s Hospital, which was assigned to Lexicon. Neither D.L.B. nor Brigham and Women\u2019s Hospital receive any income from this patent. The patent application is still pending. He has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio. He has received royalties from Elsevier (Editor, Braunwald\u2019s Heart Disease). He has been a site co-investigator for Cleerly. A.F.H. discloses research funding from American Regent, Amgen, AstraZeneca, Bayer, Beam, Boehringer Ingelheim, Crispr Therapeutics, Cytokinetics, Intellia, Merck, Novartis, Novo Nordisk, Pfizer and Verily. He has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Novartis, Novo Nordisk and Pfizer. S.D.A. discloses receiving grants from Abbott Laboratories, and personal fees from Actimed Therapeutics, Alleviant, AstraZeneca, Bayer, Berlin Heals, BioVentrix, Boehringer Ingelheim, Brahms, Cardiac Dimensions, Cardior Pharmaceuticals, Cordio, CSL Vifor, CVRx, Cytokinetics, Edwards Lifesciences, Farraday Pharmaceuticals, GSK, HeartKinetics, Impulse Dynamics, Lilly, Mankind Pharma, Medtronic, Novartis, Novo Nordisk, Occlutech, Pfizer, Regeneron, Relaxera, Repairon, SCIRENT Clinical Research and Science, Sensible Medical, Servier, Vectorious Medical Technologies, Vivus and V-Wave. He was named co-inventor of two patent applications regarding MR-proANP (DE 102007010834 and DE 102007022367), but he does not benefit personally from the related issued patents. W.S.J. discloses research funding from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Merck, the NIH, Novartis and the Patient-Centered Outcomes Research Institute. M.M. discloses employment from Boehringer Ingelheim. M.C.P. has received research funding from Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific and Pharmacosmos, and has served on committees or consulted for 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. D.S., M.S. and V.T. disclose employment from Boehringer Ingelheim. J.A.U. discloses the following relationships: advisory board membership for Boehringer Ingelheim, Novavax, Novo Nordisk and Sanofi; speaker honoraria from Amgen, AstraZeneca, Boehringer Ingelheim and Eli Lilly and Company; and research funding to his institution from Amgen, Bayer, Boehringer Ingelheim and Novartis. J.B. discloses being a consultant to Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Levator, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Pulnovo, Regeneron, Renibus, Roche, Salamandra, Salubris, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor and Zoll. J.H. declares no competing interests. The study was supported and funded by the Boehringer Ingelheim and Eli Lilly and Company Alliance. The sponsor was involved in the study design, data collection and analysis. While the sponsor was allowed to comment or edit the paper, the authors were under no obligation to incorporate such changes or to submit the paper for publication. The authors meet the criteria for authorship as recommended by the ICMJE. The authors did not receive payment related to the development of the paper. Boehringer Ingelheim was given the opportunity to review the paper for medical and scientific accuracy and intellectual property considerations.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}