{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T10:50:00Z","timestamp":1782125400260,"version":"3.54.5"},"reference-count":97,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2021,5,29]],"date-time":"2021-05-29T00:00:00Z","timestamp":1622246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Baker Trust Alice Baker and Eleanor Shaw Gender Equity Fellowship"},{"name":"Perpetual Philanthropy, Diabetes Australia"},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mineralocorticoid receptor (MR) antagonists (MRA), also referred to as aldosterone blockers, are now well-recognized for their clinical benefit in patients who have heart failure (HF) with reduced ejection fraction (HFrEF). Recent studies have also shown MRA can improve outcomes in patients with HFpEF, where the ejection fraction is preserved but left ventricular filling is reduced. While the MR is a steroid hormone receptor best known for antinatriuretic actions on electrolyte homeostasis in the distal nephron, it is now established that the MR has many physiological and pathophysiological roles in the heart, vasculature, and other nonepithelial tissue types. It is the impact of MR activation on these tissues that underpins the use of MRA in cardiovascular disease, in particular HF. This mini-review will discuss the origins and the development of MRA and highlight how their use has evolved from the \u201cpotassium-sparing diuretics\u201d spironolactone and canrenone over 60 years ago, to the more receptor-selective eplerenone and most recently the emergence of new nonsteroidal receptor antagonists esaxerenone and finerenone.<\/jats:p>","DOI":"10.1210\/endocr\/bqab105","type":"journal-article","created":{"date-parts":[[2021,5,29]],"date-time":"2021-05-29T15:08:04Z","timestamp":1622300884000},"source":"Crossref","is-referenced-by-count":15,"title":["The Role of the Mineralocorticoid Receptor and Mineralocorticoid Receptor\u2013Directed Therapies in Heart Failure"],"prefix":"10.1210","volume":"162","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0450-5375","authenticated-orcid":false,"given":"Morag J","family":"Young","sequence":"first","affiliation":[{"name":"Baker Heart and Diabetes Institute, Cardiovascular Endocrinology Laboratory, Prahran 3181, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Kanki","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Cardiovascular Endocrinology Laboratory, Prahran 3181, Australia"},{"name":"Hudson Institute of Medical Research, Victoria 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikshay","family":"Karthigan","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Cardiovascular Endocrinology Laboratory, Prahran 3181, Australia"},{"name":"Hudson Institute of Medical Research, Victoria 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penny","family":"Konstandopoulos","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Cardiovascular Endocrinology Laboratory, Prahran 3181, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,5,29]]},"reference":[{"issue":"8","key":"2021101416340764000_CIT0001","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart disease and stroke statistics-2021 update: a report from the American Heart Association","volume":"143","author":"Virani","year":"2021","journal-title":"Circulation."},{"key":"2021101416340764000_CIT0002","doi-asserted-by":"crossref","first-page":"459","DOI":"10.2147\/IJGM.S288733","article-title":"Clinical, echocardiographic, and therapeutic characteristics of heart failure in patients with preserved, mid-range, and reduced ejection fraction: future directions","volume":"14","author":"Alem","year":"2021","journal-title":"Int J Gen Med."},{"issue":"5","key":"2021101416340764000_CIT0003","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1001\/jama.2020.10262","article-title":"Heart failure with reduced ejection fraction: a review","volume":"324","author":"Murphy","year":"2020","journal-title":"JAMA."},{"issue":"2","key":"2021101416340764000_CIT0004","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s10741-019-09832-y","article-title":"Relative Efficacy of Spironolactone, Eplerenone, and cAnRenone in patients with Chronic Heart failure (RESEARCH): a systematic review and network meta-analysis of randomized controlled trials","volume":"25","author":"Frankenstein","year":"2020","journal-title":"Heart Fail Rev."},{"issue":"6","key":"2021101416340764000_CIT0005","doi-asserted-by":"crossref","first-page":"395","DOI":"10.21037\/atm.2020.03.18","article-title":"Managing heart failure with preserved ejection fraction","volume":"8","author":"Davidson","year":"2020","journal-title":"Ann Transl Med."},{"issue":"10","key":"2021101416340764000_CIT0006","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1080\/14656566.2020.1735356","article-title":"An evaluation of the fixed-dose combination sacubitril\/valsartan for the treatment of arterial hypertension","volume":"21","author":"Wehland","year":"2020","journal-title":"Expert Opin Pharmacother."},{"issue":"4","key":"2021101416340764000_CIT0007","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jchf.2020.12.009","article-title":"Mineralocorticoid receptor antagonists and SGLT2 inhibitor therapy: the best of both worlds in HFrEF","volume":"9","author":"Zannad","year":"2021","journal-title":"JACC Heart Fail."},{"issue":"10","key":"2021101416340764000_CIT0008","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. 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