{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T19:40:38Z","timestamp":1775936438162,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\u2003<\/jats:title><jats:p>To investigate the effects of spironolactone on fibrosis and cardiac function in people at increased risk of developing heart failure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results\u2003<\/jats:title><jats:p>Randomized, open-label, blinded-endpoint trial comparing spironolactone (50\u2009mg\/day) or control for up to 9 months in people with, or at high risk of, coronary disease and raised plasma B-type natriuretic peptides. The primary endpoint was the interaction between baseline serum galectin-3 and changes in serum procollagen type-III N-terminal pro-peptide (PIIINP) in participants assigned to spironolactone or control. Procollagen type-I C-terminal pro-peptide (PICP) and collagen type-1 C-terminal telopeptide (CITP), reflecting synthesis and degradation of type-I collagen, were also measured. In 527 participants (median age 73\u2009years, 26% women), changes in PIIINP were similar for spironolactone and control [mean difference (mdiff): \u22120.15; 95% confidence interval (CI) \u22120.44 to 0.15\u2009\u03bcg\/L; P\u2009=\u20090.32] but those receiving spironolactone had greater reductions in PICP (mdiff: \u22128.1; 95% CI \u221211.9 to \u22124.3\u2009\u03bcg\/L; P\u2009&amp;lt;\u20090.0001) and PICP\/CITP ratio (mdiff: \u22122.9; 95% CI \u22124.3 to \u22121.5; &amp;lt;0.0001). No interactions with serum galectin were observed. Systolic blood pressure (mdiff: \u221210; 95% CI \u221213 to \u22127\u2009mmHg; P\u2009&amp;lt;\u20090.0001), left atrial volume (mdiff: \u22121; 95% CI \u22122 to 0\u2009mL\/m2; P\u2009=\u20090.010), and NT-proBNP (mdiff: \u221257; 95% CI \u221281 to \u221233\u2009ng\/L; P\u2009&amp;lt;\u20090.0001) were reduced in those assigned spironolactone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions\u2003<\/jats:title><jats:p>Galectin-3 did not identify greater reductions in serum concentrations of collagen biomarkers in response to spironolactone. However, spironolactone may influence type-I collagen metabolism. Whether spironolactone can delay or prevent progression to symptomatic heart failure should be investigated.<\/jats:p><jats:p\/><\/jats:sec>","DOI":"10.1093\/eurheartj\/ehaa758","type":"journal-article","created":{"date-parts":[[2020,9,5]],"date-time":"2020-09-05T11:14:24Z","timestamp":1599304464000},"page":"684-696","source":"Crossref","is-referenced-by-count":120,"title":["The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart \u2018OMics\u2019 in AGEing (HOMAGE) randomized clinical trial"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1471-7016","authenticated-orcid":false,"given":"John G F","family":"Cleland","sequence":"first","affiliation":[{"name":"Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow Royal Infirmary , Glasgow G12 8QQ, UK"}]},{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d'Investigation Clinique Plurith\u00e9matique 1433, CHRU de Nancy , F-CRIN INI-CRCT, Nancy, U1116, France"}]},{"given":"Beatrice","family":"Mariottoni","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cortona Hospital , Arezzo, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7175-0464","authenticated-orcid":false,"given":"Pierpaolo","family":"Pellicori","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow Royal Infirmary , Glasgow G12 8QQ, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4339-3062","authenticated-orcid":false,"given":"Joe","family":"Cuthbert","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Hull, Castle Hill Hospital, Cottingham , East Riding of Yorkshire, UK"}]},{"given":"Job A J","family":"Verdonschot","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Maastricht University Medical Center , the Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3116-9450","authenticated-orcid":false,"given":"Johannes","family":"Petutschnigg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charit\u00e9 University Medicine Berlin, Berlin Institute of Health (BIH), and German Centre for Cardiovascular research (DZHK) , Partner Site Berlin, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9769-0180","authenticated-orcid":false,"given":"Fozia Z","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester , Oxford Road, Manchester, UK"}]},{"given":"Franco","family":"Cosmi","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d'Investigation Clinique Plurith\u00e9matique 1433, CHRU de Nancy , F-CRIN INI-CRCT, Nancy, U1116, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4356-8566","authenticated-orcid":false,"given":"Hans-Peter","family":"Brunner La Rocca","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Maastricht University Medical Center , the Netherlands"}]},{"given":"Mamas A","family":"Mamas","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester , Oxford Road, Manchester, UK"},{"name":"Centre for Prognosis Research, Institute for Primary Care and Health Sciences, Keele University , UK"}]},{"given":"Andrew L","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Hull, Castle Hill Hospital, Cottingham , East Riding of Yorkshire, UK"}]},{"given":"Frank","family":"Edelmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charit\u00e9 University Medicine Berlin, Berlin Institute of Health (BIH), and German Centre for Cardiovascular research (DZHK) , Partner Site Berlin, Germany"}]},{"given":"Burkert","family":"Pieske","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charit\u00e9 University Medicine Berlin, Berlin Institute of Health (BIH), and German Centre for Cardiovascular research (DZHK) , Partner Site Berlin, Germany"},{"name":"German Heart Center Berlin , Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9518-0953","authenticated-orcid":false,"given":"Javed","family":"Khan","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow Royal Infirmary , Glasgow G12 8QQ, UK"}]},{"given":"Ken","family":"McDonald","sequence":"additional","affiliation":[{"name":"St. Vincent's University Healthcare Group, and School of Medicine, University College Dublin , Dublin, Ireland"}]},{"given":"Philippe","family":"Rouet","sequence":"additional","affiliation":[{"name":"Equipe ob\u00e9sit\u00e9 et insuffisance cardiaque, Universit\u00e9 UPS, Inserm I2MC , Toulouse, UMR 1048, France"}]},{"given":"Jan A","family":"Staessen","sequence":"additional","affiliation":[{"name":"Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven , Leuven, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5831-0800","authenticated-orcid":false,"given":"Blerim","family":"Mujaj","sequence":"additional","affiliation":[{"name":"Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven , Leuven, Belgium"},{"name":"Department of Diagnostic and Interventional Radiology, Universitatsklinikum Freiburg , Freiburg, Germany"}]},{"given":"Arantxa","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Program of Cardiovascular Diseases, CIMA. Universidad de Navarra and IdiSNA, Pamplona, Spain CIBERCV, Carlos III Institute of Health , Madrid, Spain"}]},{"given":"Javier","family":"Diez","sequence":"additional","affiliation":[{"name":"Program of Cardiovascular Diseases, CIMA. Universidad de Navarra and IdiSNA, Pamplona, Spain CIBERCV, Carlos III Institute of Health , Madrid, Spain"},{"name":"Departments of Nephrology and Cardiology, Cl\u00ednica Universidad de Navarra , Pamplona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2151-7178","authenticated-orcid":false,"given":"Mark","family":"Hazebroek","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Maastricht University Medical Center , the Netherlands"}]},{"given":"Stephane","family":"Heymans","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Maastricht University Medical Center , the Netherlands"}]},{"given":"Roberto","family":"Latini","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche \u201cMario Negri\u201d \u2013 IRCCS , Milan, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8138-2474","authenticated-orcid":false,"given":"St\u00e9phanie","family":"Grojean","sequence":"additional","affiliation":[{"name":"Fondation Force, Research and Consulting Department, EDDH, Centre de M\u00e9decine Pr\u00e9ventive, Rue du Doyen Jacques Parisot , Vandoeuvre les Nancy, 54500, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2705-6365","authenticated-orcid":false,"given":"Anne","family":"Pizard","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d'Investigation Clinique Plurith\u00e9matique 1433, CHRU de Nancy , F-CRIN INI-CRCT, Nancy, U1116, France"}]},{"given":"Nicolas","family":"Girerd","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d'Investigation Clinique Plurith\u00e9matique 1433, CHRU de Nancy , F-CRIN INI-CRCT, Nancy, U1116, France"}]},{"given":"Patrick","family":"Rossignol","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d'Investigation Clinique Plurith\u00e9matique 1433, CHRU de Nancy , F-CRIN INI-CRCT, Nancy, U1116, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3095-277X","authenticated-orcid":false,"given":"Tim J","family":"Collier","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, London School of Hygiene and Tropical Medicine , London, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-1570","authenticated-orcid":false,"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d'Investigation Clinique Plurith\u00e9matique 1433, CHRU de Nancy , F-CRIN INI-CRCT, Nancy, U1116, France"}]},{"name":"the HOMAGE Trial Committees and Investigators","sequence":"additional","affiliation":[]},{"given":"Dan","family":"Atar","sequence":"additional","affiliation":[]},{"given":"Lars","family":"Kober","sequence":"additional","affiliation":[]},{"given":"Kenneth","family":"Dickstein","sequence":"additional","affiliation":[]},{"given":"Theis","family":"Lange","sequence":"additional","affiliation":[]}],"member":"286","published-online":{"date-parts":[[2020,11,20]]},"reference":[{"key":"2022102513282556000_ehaa758-B1","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0140-6736(17)32520-5","article-title":"Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals","volume":"391","author":"Conrad","year":"2018","journal-title":"Lancet"},{"key":"2022102513282556000_ehaa758-B2","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S0140-6736(17)32873-8","article-title":"Rising incidence of heart failure demands action","volume":"391","author":"Zannad","year":"2018","journal-title":"Lancet"},{"key":"2022102513282556000_ehaa758-B3","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1016\/j.jacc.2019.03.471","article-title":"Prevention or procrastination for heart failure? 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