{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T12:27:53Z","timestamp":1788179273242,"version":"build-2803163510"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T00:00:00Z","timestamp":1688688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T00:00:00Z","timestamp":1688688000000},"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":[[2023,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Eplerenone reduces the risk of cardiovascular death or first hospitalization for heart failure (HF) in patients with HF and a reduced ejection fraction (HFrEF), but it is still frequently underused in routine practice. We evaluated the time course of benefits of eplerenone after its initiation in HFrEF patients from the EMPHASIS-HF trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The EMPHASIS-HF trial was a double-blind randomized clinical trial assessing the effect of eplerenone in patients (n\u2009=\u20092737, mean age 68.6\u2009\u00b1\u20097.6\u2009years, 22.3% women) with HFrEF and mild symptoms. The time trajectories for the effect of eplerenone versus placebo on the primary composite endpoint (cardiovascular death or first hospitalization for HF) were investigated using Cox proportional hazards models with truncated data at each day post-randomization. A significant reduction in the primary composite endpoint was observed 26\u2009days after randomization (hazard ratio 0.58; 95% confidence interval, 0.34\u20131.00, p\u2009=\u20090.049). Eplerenone was first associated with a significant reduction in the primary endpoint in 35\u2009days or less in most subgroups, including patients with HF history \u226518\u2009months (day 24), estimated glomerular filtration rate\u2009&amp;lt;60\u2009ml\/min (day 12), ischaemic HF aetiology (day 28), age\u2009\u226565\u2009years (day 28), narrow QRS (day 30), higher MAGGIC score (day 35), lower potassium (day 30), left ventricular ejection fraction \u226530% (day 28) or already treated with beta-blockers (day 25).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Eplerenone provides statistically significant and clinically meaningful benefits shortly after treatment initiation in most patients, irrespective of clinical profile. This result reinforces the need for an early initiation of eplerenone in HFrEF, as part of rapidly instituting guideline-directed medical therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2952","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T23:34:50Z","timestamp":1687908890000},"page":"1444-1449","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Time to Clinical Benefit of Eplerenone Among Patients with Heart Failure and Reduced Ejection Fraction: A Subgroups Analysis from the EMPHASIS-HF Trial"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2958-943X","authenticated-orcid":false,"given":"Luca","family":"Monzo","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Lorraine, Centre d'Investigations Cliniques Plurith\u00e9matique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Girerd","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Centre d'Investigations Cliniques Plurith\u00e9matique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Duarte","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Centre d'Investigations Cliniques Plurith\u00e9matique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Centre d'Investigations Cliniques Plurith\u00e9matique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) , Nancy ,","place":["France"]},{"name":"Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto , Porto ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Research Centre, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Thorax Center, University Medical Center , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Swedberg","sequence":"additional","affiliation":[{"name":"Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart J.","family":"Pocock","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, London School of Hygiene & Tropical Medicine , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"McGill University Health Centre , Montreal, Quebec ,","place":["Canada"]},{"name":"Department of Medicine, University of Michigan School of Medicine , Ann Arbor, MI ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Centre d'Investigations Cliniques Plurith\u00e9matique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) , Nancy 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