{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:22:52Z","timestamp":1790011372186,"version":"4.0.1"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T00:00:00Z","timestamp":1550188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T00:00:00Z","timestamp":1550188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Current heart failure guidelines recommend target eplerenone dose of 50\u2009mg\/day. We have examined the effect of different eplerenone doses based on pre-specified renal function stratification in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In EMPHASIS-HF, the target dose of eplerenone\/placebo was stratified at randomization according to estimated glomerular filtration rate (eGFR): 50\u2009mg\/day if eGFR \u2265\u200950\u2009mL\/min\/1.73\u2009m2 and \u2264\u200925\u2009mg\/day if eGFR 30\u201349\u2009mL\/min\/1.73\u2009m2. Patients remained within these dose ranges during the trial (as per stratification). The primary outcome was a composite of heart failure hospitalization or cardiovascular mortality. Eplerenone was superior to placebo within each respective eGFR stratum [eplerenone vs. placebo in the eGFR \u2265\u200950\u2009mL\/min\/1.73\u2009m2 stratum: hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.45\u20130.74; and eplerenone vs. placebo in the eGFR 30\u201349\u2009mL\/min\/1.73\u2009m2 stratum: HR\u20090.62, 95% CI 0.49\u20130.78; Pinteraction\u2009=\u20090.89]. Despite receiving lower eplerenone doses, patients in the eGFR 30\u201349\u2009mL\/min\/1.73\u2009m2 stratum more often had hyperkalaemia, renal failure events, and drug discontinuation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In EMPHASIS-HF the eplerenone dose was stratified according to renal function and the treatment effect was not influenced by renal function: 25\u2009mg\/day in patients with eGFR 30\u201349\u2009mL\/min\/1.73\u2009m2 was as effective as 50\u2009mg\/day in patients with eGFR\u2009&amp;gt;\u2009=50\u2009mL\/min\/1.73\u2009m2. However, patients with impaired renal function experienced more adverse events, despite reveiving lower eplerenone doses. Current guidelines do not recommend tailoring the dose of eplereone according to renal function but the current data suggest they should.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1400","type":"journal-article","created":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T07:53:53Z","timestamp":1550217233000},"page":"345-351","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Renal Function Stratified Dose Comparisons of Eplerenone Versus Placebo in the EMPHASIS-HF Trial"],"prefix":"10.1093","volume":"21","author":[{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"first","affiliation":[{"name":"National Institute of Health and Medical Research (INSERM), Center for Clinical Multidisciplinary Research 1433, INSERM U1116, University of Lorraine, Regional University Hospital of Nancy, French Clinical Research Infrastructure Network (F-CRIN) Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists (INI-CRCT) , Nancy ,","place":["France"]},{"name":"Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, Cardiovascular Research and Development Unit, University of Porto , Porto ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Abreu","sequence":"additional","affiliation":[{"name":"Pfizer Inc. , New York, NY ,","place":["USA"]}],"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":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Swedberg","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Medicine, 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 and Tropical Medicine , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Vincent","sequence":"additional","affiliation":[{"name":"Pfizer Inc. , New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Lins","sequence":"additional","affiliation":[{"name":"Pfizer Inc. , New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Rossignol","sequence":"additional","affiliation":[{"name":"National Institute of Health and Medical Research (INSERM), Center for Clinical Multidisciplinary Research 1433, INSERM U1116, University of Lorraine, Regional University Hospital of Nancy, French Clinical Research Infrastructure Network (F-CRIN) Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists (INI-CRCT) , 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":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"National Institute of Health and Medical Research (INSERM), Center for Clinical Multidisciplinary Research 1433, INSERM U1116, University of Lorraine, Regional University Hospital of Nancy, French Clinical Research Infrastructure Network (F-CRIN) Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists (INI-CRCT) , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,2,15]]},"reference":[{"key":"2026011721293773400_ejhf1400-bib-0001","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ejhf.592","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). 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