{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T08:58:11Z","timestamp":1782205091877,"version":"3.54.5"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":2405,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T00:00:00Z","timestamp":1560902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008349","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008349","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Heart failure (HF) is associated with considerable symptom burden and impairment in physical functioning and quality of life. The sodium\u2013glucose co-transporter 2 inhibitor empagliflozin reduced the risk of HF hospitalisation and cardiovascular death in patients with type 2 diabetes and established cardiovascular disease in the EMPA-REG OUTCOME trial, and could potentially improve congestion symptoms and exercise capacity in patients with HF. We describe the designs of the EMPERIAL-Preserved and EMPERIAL-Reduced trials of empagliflozin in patients with chronic stable HF, with or without type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>EMPERIAL-Preserved and EMPERIAL-Reduced are randomised, placebo-controlled trials designed to investigate the effects of empagliflozin on exercise capacity and patient-reported outcomes in patients with chronic stable HF with preserved ejection fraction [HFpEF; left ventricular ejection fraction (LVEF) &amp;gt;\u200940%] and HF with reduced ejection fraction (HFrEF; LVEF \u2264\u200940%), respectively. In each trial, approximately 300 patients will be randomised 1:1 to receive empagliflozin 10 mg or placebo once daily for 12\u2009weeks. In both trials, the primary endpoint is the change from baseline in 6-min walk test distance at week 12. Key secondary endpoints are the change from baseline in Kansas City Cardiomyopathy Questionnaire total symptom score and change from baseline in dyspnoea score of the Chronic Heart Failure Questionnaire at week 12.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The EMPERIAL-Preserved and EMPERIAL-Reduced trials will determine the effects of empagliflozin on exercise capacity and patient-reported outcomes in patients with HFpEF and HFrEF, respectively, and provide insight into the potential of empagliflozin in the treatment of patients with HF.<\/jats:p>\n                    <jats:p>Clinical Trial Registration: ClinicalTrials.gov ID: NCT03448406 (EMPERIAL-Preserved), NCT03448419 (EMPERIAL-Reduced).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1486","type":"journal-article","created":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T01:13:32Z","timestamp":1560993212000},"page":"932-942","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Rationale and Design of The Emperial-Preserved and Emperial-Reduced Trials of Empagliflozin in Patients with Chronic Heart Failure"],"prefix":"10.1093","volume":"21","author":[{"given":"William T.","family":"Abraham","sequence":"first","affiliation":[{"name":"The Ohio State University , Columbus, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[{"name":"Wroclaw Medical University , Wroclaw ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Brueckmann","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH , Ingelheim ,","place":["Germany"]},{"name":"Faculty of Medicine Mannheim, University of Heidelberg , Mannheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cordula","family":"Zeller","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemani","family":"Macesic","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim (Canada) Ltd , Burlington ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Peil","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG , Ingelheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mich\u00e8le","family":"Brun","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim France , Reims Cedex ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Ustyugova","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH , Ingelheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waheed","family":"Jamal","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH , Ingelheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshin","family":"Salsali","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn","family":"Lindenfeld","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , Nashville, TN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Division of Cardiology and Metabolism, Department of Cardiology (CVK), Berlin-Brandenburg Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) Partner Site Berlin, Charit\u00e9 Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]},{"name":"Department of Cardiology and Pneumology, University Medicine G\u00f6ttingen (UMG) , G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,19]]},"reference":[{"key":"2026011721311485600_ejhf1486-bib-0001","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.jacc.2013.11.053","article-title":"The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries","volume":"63","author":"Ambrosy","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"2026011721311485600_ejhf1486-bib-0002","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1136\/heartjnl-2017-311652","article-title":"Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis","volume":"104","author":"Zheng","year":"2018","journal-title":"Heart"},{"key":"2026011721311485600_ejhf1486-bib-0003","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.jacc.2007.04.064","article-title":"Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: a report from the OPTIMIZE-HF Registry","volume":"50","author":"Fonarow","year":"2007","journal-title":"J Am Coll Cardiol"},{"key":"2026011721311485600_ejhf1486-bib-0004","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jacc.2005.09.022","article-title":"Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database","volume":"47","author":"Yancy","year":"2006","journal-title":"J Am Coll Cardiol"},{"key":"2026011721311485600_ejhf1486-bib-0005","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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