{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T01:51:28Z","timestamp":1794361888968,"version":"4.9.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T00:00:00Z","timestamp":1582070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T00:00:00Z","timestamp":1582070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Women with heart failure (HF) are under-represented in individual randomized clinical trials (RCTs). Little is known about sex-specific treatment effects in HF medications. We evaluated sex differences in the response to mineralocorticoid receptor antagonists (MRAs) in major HF MRA trials, including a broad spectrum of left ventricular ejection fraction (LVEF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Individual patient data fixed-effect meta-analysis was performed using 6167 patients (31.4% were women) recruited in three placebo-controlled RCTs: Randomized Aldactone Evaluation Study (RALES), Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) and Spironolactone for Heart Failure with Preserved Ejection Fraction (TOPCAT)-Americas. Compared to men, women were older, had higher body mass index and lower glomerular filtration rate. They also had higher LVEF and poorer New York Heart Association functional class and were less likely to be taking angiotensin-converting enzyme inhibitors\/angiotensin II receptor blockers. Placebo-arm event rates were lower for women compared with men (15.4 vs. 22.1 per 100\u2009person-year; P = 0.002). MRAs reduced consistently, in men and women, the relative risk for cardiovascular death or HF hospitalization (P for interaction = 0.83), cardiovascular death (P for interaction = 0.44) and all-cause death (P for interaction = 0.19). These findings remained consistent after adjustment for potential confounders, regardless of LVEF. There was no sex-specific impact of MRA on the rate of hyperkalaemia and worsening renal function during the median 22\u2009months of follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In three large MRA RCTs, women were substantially different from men with regard to their clinical features and event rates. Nonetheless, this meta-analysis supports a consistent and beneficial MRA effect regardless of sex.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1740","type":"journal-article","created":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T23:46:56Z","timestamp":1582156016000},"page":"834-844","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Sex Differences in Mineralocorticoid Receptor Antagonist Trials: A Pooled Analysis of Three Large Clinical Trials"],"prefix":"10.1093","volume":"22","author":[{"given":"Xavier","family":"Rossello","sequence":"first","affiliation":[{"name":"Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) , Madrid ,","place":["Spain"]},{"name":"Department of Cardiology, Hospital Universitari Son Espases (HUSE) , Mallorca ,","place":["Spain"]},{"name":"CIBER de enfermedades CardioVasculares (CIBERCV) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Centre d\u2019Investigation Clinique-Plurith\u00e9matique INSERM CIC-P 1433, and INSERM U1116, CHRU Nancy Brabois, F-CRIN INI-CRCT, Universit\u00e9 de Lorraine , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart J.","family":"Pocock","sequence":"additional","affiliation":[{"name":"Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) , Madrid ,","place":["Spain"]},{"name":"London School of Hygiene and Tropical Medicine , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn S.P.","family":"Lam","sequence":"additional","affiliation":[{"name":"National Heart Centre Singapore \u00a0","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Girerd","sequence":"additional","affiliation":[{"name":"Centre d\u2019Investigation Clinique-Plurith\u00e9matique INSERM CIC-P 1433, and INSERM U1116, CHRU Nancy Brabois, F-CRIN INI-CRCT, Universit\u00e9 de Lorraine , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Michigan School of Medicine , Ann Arbor, MI ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Rossignol","sequence":"additional","affiliation":[{"name":"Centre d\u2019Investigation Clinique-Plurith\u00e9matique INSERM CIC-P 1433, and INSERM U1116, CHRU Nancy Brabois, F-CRIN INI-CRCT, Universit\u00e9 de Lorraine , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Centre d\u2019Investigation Clinique-Plurith\u00e9matique INSERM CIC-P 1433, and INSERM U1116, CHRU Nancy Brabois, F-CRIN INI-CRCT, Universit\u00e9 de Lorraine , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,2,19]]},"reference":[{"key":"2026011721352046000_ejhf1740-bib-0001","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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