{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T05:08:18Z","timestamp":1782623298983,"version":"3.54.5"},"reference-count":17,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T00:00:00Z","timestamp":1567468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Trials using mineralocorticoid receptor antagonists (MRAs) in myocardial infraction (MI) without heart failure (HF) or systolic impairment have been underpowered to assess morbidity\u2010mortality benefit. In EPHESUS 6632 patients were included, of whom 11% had an ejection fraction (EF) of 40% and HF or diabetes. We aim to assess the potential benefit of MRAs in MI with EF of 40%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cox models with interaction term for EF. The primary outcome was a composite of cardiovascular death or hospitalization for cardiovascular reasons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Hypothesis<\/jats:title><jats:p>Patients with an EF of 40% benefit similarly from MRA therapy to those with an EF &lt;40%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In EPHESUS, 753 patients had an EF = 40% and 5864 an EF\u2009&lt;\u200940%. Patients with an EF = 40% were younger (63 vs 64\u2009years), had lower heart rate (73 vs 75\u2009bpm), less atrial fibrillation (10% vs 14%), previous MI (21% vs 28%), HF hospitalization (5% vs 8%), and had more often reperfusion therapy and\/or revascularization (55% vs 44%). The mean EF was 40.0\u2009\u00b1\u20090.3% in those with EF = 40% vs 32.2\u2009\u00b1\u20095.9% in those with EF\u2009&lt;\u200940%. The primary outcome occurred in 13.3% (10 events per 100\u2009py) of the patients with EF = 40% vs 22.9% (19 events per 100\u2009py) in those with EF\u2009&lt;\u200940%; adjusted HR for EF = 40% vs &lt;40% = 0.65 (0.53\u20100.81). Eplerenone reduced the event\u2010rate homogenously regardless of EF (interaction<jats:sub>\n<jats:italic>p<\/jats:italic><\/jats:sub> EF = 40% vs EF\u2009&lt;\u200940% = 0.21). Similar findings were observed for cardiovascular and all\u2010cause death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Eplerenone reduces hospitalizations and mortality in patients with MI and EF = 40% similarly to patients with EF\u2009&lt;\u200940%. These findings suggest that MI patients with EF in the \u201cmid\u2010range zone\u201d may also benefit from MRA therapy which might help clinicians in their treatment decisions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clc.23261","type":"journal-article","created":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T06:33:02Z","timestamp":1567578782000},"page":"1106-1112","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Eplerenone in patients with myocardial infarction and \u201cmid\u2010range\u201d ejection fraction: An analysis from the EPHESUS trial"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2304-6138","authenticated-orcid":false,"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Lorraine, Centre d'Investigation Clinique\u2010 Plurith\u00e9matique Inserm CIC\u2010P 1433  Nancy France"},{"name":"Inserm U1116, CHRU Nancy Brabois, F\u2010CRIN INI\u2010CRCT (Cardiovascular and Renal Clinical Trialists)  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Rossello","sequence":"additional","affiliation":[{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC)  Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Cardiovasculares (CIBERCV)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Michigan School of Medicine  Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Rossignol","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Centre d'Investigation Clinique\u2010 Plurith\u00e9matique Inserm CIC\u2010P 1433  Nancy France"},{"name":"Inserm U1116, CHRU Nancy Brabois, F\u2010CRIN INI\u2010CRCT (Cardiovascular and Renal Clinical Trialists)  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Centre d'Investigation Clinique\u2010 Plurith\u00e9matique Inserm CIC\u2010P 1433  Nancy France"},{"name":"Inserm U1116, CHRU Nancy Brabois, F\u2010CRIN INI\u2010CRCT (Cardiovascular and Renal Clinical Trialists)  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.592"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.05.011"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-015-0033-1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcvp\/pvw016"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.001583"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.015884"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu164"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.02.033"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011119003788"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1149"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.561423"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht247"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2018.02.014"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-018-1378-0"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2018-312950"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800781"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1400"}],"container-title":["Clinical 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