{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:18:20Z","timestamp":1787008700156,"version":"build-2736575974"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:00:00Z","timestamp":1605052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100018507","name":"Japan Medical Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018507","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>A mineralocorticoid receptor antagonist (MRA) is effective in patients with chronic heart failure; however, the effects of the early initiation of an MRA in patients with acute heart failure (AHF) have not been elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In this multicentre, randomized, double-blind, placebo-controlled, parallel-group study, we focused on the safety and effectiveness of the treatment with eplerenone, a selective MRA in 300 patients with AHF, that is, 149 in the eplerenone group and 151 in the placebo group in 27 Japanese institutions. The key inclusion criteria were (i) patients aged 20\u2009years or older and (ii) those with left ventricular ejection fraction of \u226440%. The primary outcome was a composite of cardiac death or first re-hospitalization due to cardiovascular disease within 6\u2009months. The mean age of the participants was 66.8\u2009years, 27.3% were women, and the median levels of brain natriuretic peptide were 376.0\u2009pg\/mL. The incidences of the primary outcome were 19.5% in the eplerenone group and 17.2% in the placebo group [hazard ratio (HR): 1.09, 95% confidence interval (CI): 0.642\u20131.855]. In prespecified secondary outcomes, HR for the composite endpoint, cardiovascular death, or first re-hospitalization due to heart failure within 6\u2009months was 0.55 (95% CI: 0.213\u20131.434). The safety profile for eplerenone was as expected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The early initiation of eplerenone in patients with AHF could safely be utilized. The reduction of the incidence of a composite of cardiovascular death or first re-hospitalization for cardiovascular diseases by eplerenone is inconclusive because of inadequate power.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjcvp\/pvaa132","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T07:10:15Z","timestamp":1604387415000},"page":"108-117","source":"Crossref","is-referenced-by-count":40,"title":["Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure (EARLIER trial): a multicentre, randomized, double-blind, placebo-controlled trial"],"prefix":"10.1093","volume":"8","author":[{"given":"Masanori","family":"Asakura","sequence":"first","affiliation":[{"name":"Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine, Hyogo, Japan"},{"name":"Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Yamada","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Osaka General Medical Center, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Nara Medical University, Nara Medical University Hospital, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Kimura","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Yokohama City University Medical Center, Yokohama, 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Tsujimoto","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Veritas Hospital, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6775-6940","authenticated-orcid":false,"given":"Yukio","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Osaka City General Hospital, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yorihiko","family":"Higashino","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Higashi Takarazuka Satoh Hospital, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yodo","family":"Tamaki","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tenri Hospital, Nara, Tenri, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Sugino","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Niinuma","sequence":"additional","affiliation":[{"name":"Department of Cardiology, St. Luke's International Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Okuhara","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine, Hyogo, 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Graduate School of Medical Science, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroya","family":"Kawai","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Hyogo Prefectural Himeji Cardiovascular Center, Hyogo Brain and Heart Center, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Satoh","sequence":"additional","affiliation":[{"name":"Department of Cardiology, National Hospital Organization Disaster Medical Center, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-Ichi","family":"Hirata","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Yokoi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cardiac Arrhythmia Center, Kishiwada Tokushukai Hospital, Kishiwada, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshisato","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Miyazaki Medical Association Hospital, Miyazaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Maejima","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Tokyo Medical and Dental University Medical Hospital, Tokyo, 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Developed in collaboration with the heart failure association (HFA) of the esc","volume":"14","author":"McMurray","year":"2012","journal-title":"Eur J Heart Fail"},{"key":"2022030710594695200_pvaa132-B4","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1016\/j.ijcard.2012.10.007","article-title":"The past, present and future of renin-angiotensin aldosterone system inhibition","volume":"167","author":"Mentz","year":"2013","journal-title":"Int J Cardiol"},{"key":"2022030710594695200_pvaa132-B5","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.jacc.2011.03.057","article-title":"Influence of global region on outcomes in heart failure beta-blocker trials","volume":"58","author":"O'Connor","year":"2011","journal-title":"J Am Coll Cardiol"},{"key":"2022030710594695200_pvaa132-B6","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10741-005-6127-6","article-title":"Overview of acutely decompensated congestive heart failure (ADHF): a report from the ADHERE registry","volume":"9","author":"Fonarow","year":"2005","journal-title":"Heart Fail Rev"},{"key":"2022030710594695200_pvaa132-B7","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1253\/circj.CJ-13-0187","article-title":"Clinical features and outcome in hospitalized heart failure in Japan (from the ATTEND registry)","volume":"77","author":"Sato","year":"2013","journal-title":"Circ J"},{"key":"2022030710594695200_pvaa132-B8","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jacc.2005.03.051","article-title":"In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the acute decompensated heart failure national registry (ADHERE)","volume":"46","author":"Abraham","year":"2005","journal-title":"J Am Coll Cardiol"},{"key":"2022030710594695200_pvaa132-B9","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1056\/NEJMoa1100171","article-title":"Effect of nesiritide in patients with acute decompensated heart failure","volume":"365","author":"O'Connor","year":"2011","journal-title":"N Engl J Med"},{"key":"2022030710594695200_pvaa132-B10","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1056\/NEJMoa1801291","article-title":"Effects of serelaxin in patients with acute heart failure","volume":"381","author":"Metra","year":"2019","journal-title":"N Engl J Med"},{"key":"2022030710594695200_pvaa132-B11","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1056\/NEJMoa1812851","article-title":"Angiotensin\u2013neprilysin inhibition in acute decompensated heart failure","volume":"380","author":"Velazquez","year":"2019","journal-title":"N Engl J Med"},{"key":"2022030710594695200_pvaa132-B12","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1161\/01.CIR.0000071081.35693.9A","article-title":"Eplerenone: cardiovascular protection","volume":"107","author":"Brown","year":"2003","journal-title":"Circulation"},{"key":"2022030710594695200_pvaa132-B13","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1210\/jc.2003-030490","article-title":"50th anniversary of aldosterone","volume":"88","author":"Williams","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2022030710594695200_pvaa132-B14","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1093\/eurjhf\/hft100","article-title":"Serum aldosterone is associated with mortality and re-hospitalization in patients with reduced ejection fraction hospitalized for acute heart failure: analysis from the EVEREST trial","volume":"15","author":"Girerd","year":"2013","journal-title":"Eur J Heart Fail"},{"key":"2022030710594695200_pvaa132-B15","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s10741-011-9280-0","article-title":"A comprehensive, longitudinal description of the in-hospital and post-discharge clinical, laboratory, and neurohormonal course of patients with heart failure who die or are re-hospitalized within 90 days: analysis from the EVEREST trial","volume":"17","author":"Gheorghiade","year":"2012","journal-title":"Heart Fail Rev"},{"key":"2022030710594695200_pvaa132-B16","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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