{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T13:36:06Z","timestamp":1769088966485,"version":"3.49.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":3828,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T00:00:00Z","timestamp":1438041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"COST ADMIRE"},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"name":"COST ADMIRE"},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The selective mineralocorticoid receptor (MR) antagonist eplerenone given early in patients with acute myocardial infarction (MI) improves clinical outcome, whereas little is known about the effectiveness of early spironolactone therapy. We aimed to compare the ability of eplerenone and spironolactone to promote cardiac repair after experimental MI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Starting immediately after coronary artery ligation, C57BL\/6J mice were treated with placebo, eplerenone, or spironolactone. At 7\u2009days, treatment with eplerenone orspironolactone reduced thinning and expansion of healing infarct and improved early left ventricular chamber enlargement. Remarkably, eplerenone therapy resulted in significantly greater improvement than spironolactone of left ventricular contractile function and relaxation, associated with a more considerable leftward and downward shift of the pressure volume curve. Seven-day survival rate was significantly increased only in eplerenone treated mice. Moreover, eplerenone was superior to spironolactone in amelioratin neovessel formation in the injured myocardium. Optimized flow cytometry analysis of the monocyte differentiation marker Ly6C revealed predominant accumulation of Ly6Chigh monocytes\/macrophages at the site of ischemic injury during the early inflammatory phase in placebo-treated mice. In contrast, MR antagonism, especially by eplerenone, led to a skewing of the monocyte\/macrophage population toward a higher frequency of healing promoting Ly6Clow cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The MR antagonist eplerenone versus spironolactone showed superiorefficacy during the acute MI phase with more beneficial effects on survival, early cardiac dilation, and functional decline. Modulation of monocyte maturation and enhanced infarct neovessel formation appears to play a pivotal role.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.12053","type":"journal-article","created":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T11:36:51Z","timestamp":1438083411000},"page":"150-158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Efficacy of Mineralocorticoid Receptor Antagonism in the Acute Myocardial Infarction Phase: Eplerenone Versus Spironolactone"],"prefix":"10.1093","volume":"2","author":[{"given":"Daniela","family":"Fraccarollo","sequence":"first","affiliation":[{"name":"Klinik fuer Kardiologie und Angiologie, Medizinische Hochschule Hannover , Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Galuppo","sequence":"additional","affiliation":[{"name":"Klinik fuer Kardiologie und Angiologie, Medizinische Hochschule Hannover , Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan-Thorben","family":"Sieweke","sequence":"additional","affiliation":[{"name":"Klinik fuer Kardiologie und Angiologie, Medizinische Hochschule Hannover , Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. Christian","family":"Napp","sequence":"additional","affiliation":[{"name":"Klinik fuer Kardiologie und Angiologie, Medizinische Hochschule Hannover , Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Grobbecker","sequence":"additional","affiliation":[{"name":"Beckman Coulter GmbH , Krefeld ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johann","family":"Bauersachs","sequence":"additional","affiliation":[{"name":"Klinik fuer Kardiologie und Angiologie, Medizinische Hochschule Hannover , Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,7,28]]},"reference":[{"key":"2026012115144496500_ehf212053-bib-0001","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/ejhf.43","article-title":"Heart failure highlights in 2012\u20132013","volume":"16","author":"Liu","year":"2014","journal-title":"Eur J Heart Fail"},{"key":"2026012115144496500_ehf212053-bib-0002","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1093\/cvr\/cvs109","article-title":"Novel therapeutic approaches to post-infarction remodelling","volume":"94","author":"Fraccarollo","year":"2012","journal-title":"Cardiovasc Res"},{"key":"2026012115144496500_ehf212053-bib-0003","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1056\/NEJM199909023411001","article-title":"The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators","volume":"341","author":"Pitt","year":"1999","journal-title":"N Engl J Med"},{"key":"2026012115144496500_ehf212053-bib-0004","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1056\/NEJMoa030207","article-title":"Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction","volume":"348","author":"Pitt","year":"2003","journal-title":"N Engl J Med"},{"key":"2026012115144496500_ehf212053-bib-0005","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1161\/HYPERTENSIONAHA.114.04488","article-title":"Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist treatment in cardiac and renal diseases","volume":"65","author":"Bauersachs","year":"2015","journal-title":"Hypertension"},{"key":"2026012115144496500_ehf212053-bib-0006","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa1009492","article-title":"Eplerenone in patients with systolic heart failure and mild symptoms","volume":"364","author":"Zannad","year":"2011","journal-title":"N Engl J Med"},{"key":"2026012115144496500_ehf212053-bib-0007","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/ejhf.31","article-title":"Selection of a mineralocorticoid receptor antagonist for patients with hypertension or heart failure","volume":"16","author":"Iqbal","year":"2014","journal-title":"Eur J Heart Fail"},{"key":"2026012115144496500_ehf212053-bib-0008","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1093\/eurjhf\/hfp136","article-title":"Timing of eplerenone initiation and outcomes in patients with heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction: insights from the EPHESUS trial","volume":"11","author":"Adamopoulos","year":"2009","journal-title":"Eur J Heart Fail"},{"key":"2026012115144496500_ehf212053-bib-0009","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1093\/eurheartj\/ehu164","article-title":"Early eplerenone treatment in patients with acute ST-elevation myocardial infarction without heart failure: the randomized double-blind Reminder study","volume":"35","author":"Montalescot","year":"2014","journal-title":"Eur Heart J"},{"key":"2026012115144496500_ehf212053-bib-0010","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.1172\/JCI41080","article-title":"Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice","volume":"120","author":"Usher","year":"2010","journal-title":"J Clin Invest"},{"key":"2026012115144496500_ehf212053-bib-0011","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1161\/HYPERTENSIONAHA.107.100941","article-title":"Immediate mineralocorticoid receptor blockade improves myocardial infarct healing by modulation of the inflammatory response","volume":"51","author":"Fraccarollo","year":"2008","journal-title":"Hypertension"},{"key":"2026012115144496500_ehf212053-bib-0012","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1161\/01.CIR.0000163562.82134.8E","article-title":"Persistent cardiac aldosterone synthesis in angiotensin II type 1A receptor-knockout mice after myocardial infarction","volume":"111","author":"Katada","year":"2005","journal-title":"Circulation"},{"key":"2026012115144496500_ehf212053-bib-0013","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1161\/01.CIR.99.20.2694","article-title":"Activation of cardiac aldosterone production in rat myocardial infarction: effect of angiotensin II receptor blockade and role in cardiac fibrosis","volume":"99","author":"Silvestre","year":"1999","journal-title":"Circulation"},{"key":"2026012115144496500_ehf212053-bib-0014","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1161\/CIRCULATIONAHA.110.983023","article-title":"Deletion of cardiomyocyte mineralocorticoid receptor ameliorates adverse remodeling after myocardial infarction","volume":"123","author":"Fraccarollo","year":"2011","journal-title":"Circulation"},{"key":"2026012115144496500_ehf212053-bib-0015","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/clc.20324","article-title":"A comparison of the aldosterone-blocking agents eplerenone and spironolactone","volume":"31","author":"Struthers","year":"2008","journal-title":"Clin Cardiol"},{"key":"2026012115144496500_ehf212053-bib-0016","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1093\/eurjhf\/hfs067","article-title":"Eplerenone and new-onset diabetes in patients with mild heart failure: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF)","volume":"14","author":"Preiss","year":"2012","journal-title":"Eur J Heart Fail"},{"key":"2026012115144496500_ehf212053-bib-0017","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.ahj.2010.04.024","article-title":"Effect of eplerenone versus spironolactone on cortisol and hemoglobin A(1)(c) levels in patients with chronic heart failure","volume":"160","author":"Yamaji","year":"2010","journal-title":"Am Heart J"},{"key":"2026012115144496500_ehf212053-bib-0018","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1007\/s00125-004-1510-8","article-title":"Spironolactone impairs endothelial function and heart rate variability in patients with type 2 diabetes","volume":"47","author":"Davies","year":"2004","journal-title":"Diabetologia"},{"key":"2026012115144496500_ehf212053-bib-0019","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1007\/s00125-008-0972-5","article-title":"Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles","volume":"51","author":"Swaminathan","year":"2008","journal-title":"Diabetologia"},{"key":"2026012115144496500_ehf212053-bib-0020","doi-asserted-by":"crossref","first-page":"915","DOI":"10.2337\/dc08-1709","article-title":"Predictors of development of diabetes in patients with chronic heart failure in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program","volume":"32","author":"Preiss","year":"2009","journal-title":"Diabetes Care"},{"key":"2026012115144496500_ehf212053-bib-0021","doi-asserted-by":"crossref","first-page":"4410","DOI":"10.4049\/jimmunol.172.7.4410","article-title":"Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response","volume":"172","author":"Sunderkotter","year":"2004","journal-title":"J Immunol"},{"key":"2026012115144496500_ehf212053-bib-0022","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1161\/CIRCRESAHA.114.303204","article-title":"Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium","volume":"114","author":"Hilgendorf","year":"2014","journal-title":"Circ Res"},{"key":"2026012115144496500_ehf212053-bib-0023","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1126\/science.1178331","article-title":"Development of monocytes, macrophages, and dendritic cells","volume":"327","author":"Geissmann","year":"2010","journal-title":"Science"},{"key":"2026012115144496500_ehf212053-bib-0024","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1093\/eurjhf\/hfr122","article-title":"The role of monocytes and inflammation in the pathophysiology of heart failure","volume":"13","author":"Wrigley","year":"2011","journal-title":"Eur J Heart Fail"},{"key":"2026012115144496500_ehf212053-bib-0025","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1038\/nbt.1989","article-title":"Therapeutic siRNA silencing in inflammatory monocytes in mice","volume":"29","author":"Leuschner","year":"2011","journal-title":"Nat Biotechnol"},{"key":"2026012115144496500_ehf212053-bib-0026","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1161\/CIRCULATIONAHA.111.052126","article-title":"Regulatory role of dendritic cells in postinfarction healing and left ventricular remodeling","volume":"125","author":"Anzai","year":"2012","journal-title":"Circulation"},{"key":"2026012115144496500_ehf212053-bib-0027","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1161\/CIRCULATIONAHA.111.044164","article-title":"Activation of CD4+ T lymphocytes improves wound healing and survival after experimental myocardial infarction in mice","volume":"125","author":"Hofmann","year":"2012","journal-title":"Circulation"},{"key":"2026012115144496500_ehf212053-bib-0028","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jacc.2009.04.021","article-title":"Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction","volume":"54","author":"Tsujioka","year":"2009","journal-title":"J Am Coll Cardiol"},{"key":"2026012115144496500_ehf212053-bib-0029","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1161\/01.CIR.0000068340.96506.0F","article-title":"Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction","volume":"107","author":"Hayashi","year":"2003","journal-title":"Circulation"},{"key":"2026012115144496500_ehf212053-bib-0030","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.ahj.2010.06.049","article-title":"Rationale for an early aldosterone blockade in acute myocardial infarction and design of the ALBATROSS trial","volume":"160","author":"Beygui","year":"2010","journal-title":"Am Heart J"},{"key":"2026012115144496500_ehf212053-bib-0031","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.amjmed.2011.12.018","article-title":"Eplerenone is not superior to older and less expensive aldosterone antagonists","volume":"125","author":"Chatterjee","year":"2012","journal-title":"Am J Med"},{"key":"2026012115144496500_ehf212053-bib-0032","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.jval.2012.01.004","article-title":"Cost-effectiveness of aldosterone antagonists for the treatment of post-myocardial infarction heart failure","volume":"15","author":"McKenna","year":"2012","journal-title":"Value Health"},{"key":"2026012115144496500_ehf212053-bib-0033","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nrcardio.2013.60","article-title":"Cost-effectiveness of heart failure therapies","volume":"10","author":"Rohde","year":"2013","journal-title":"Nat Rev Cardiol"}],"container-title":["ESC Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fehf2.12053","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fehf2.12053","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ehf2.12053","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ehf2.12053","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/2\/3\/150\/66226022\/eschf_2_3_150.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/2\/3\/150\/66226022\/eschf_2_3_150.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T20:19:47Z","timestamp":1769026787000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eschf\/article\/2\/3\/150\/8413215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,28]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,7,28]]},"published-print":{"date-parts":[[2015,9,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ehf2.12053","relation":{},"ISSN":["2055-5822"],"issn-type":[{"value":"2055-5822","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,9]]},"published":{"date-parts":[[2015,7,28]]},"assertion":[{"value":"2015-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-06-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-07-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}