{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:57:40Z","timestamp":1792191460278,"version":"4.4.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T00:00:00Z","timestamp":1703808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Frailty is a severe, common co\u2010morbidity associated with heart failure (HF) with preserved ejection fraction (HFpEF). The impact of frailty on HFpEF outcomes may affect treatment choices in HFpEF. The impact of frailty on HFpEF patients and any impact on the clinical benefits of sodium glucose co\u2010transporter 2 (SGLT2) inhibition in HFpEF have been described in only a limited number of trials. Whether the SGLT2 inhibitor empagliflozin would improve or worsen frailty status when given to HFpEF patients is also not known. The aims of this study were, therefore, to evaluate, in HFpEF patients enrolled in the EMPEROR\u2010Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), the impact of frailty on clinical outcomes, and on the effects of empagliflozin, as well as the effect of empagliflozin on frailty status during treatment period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We calculated a cumulative deficit\u2010derived frailty index (FI) using 44 variables including clinical, laboratory and quality of life parameters recorded in EMPEROR\u2010Preserved. Patients were classified into four groups: non\u2010frail (FI\u00a0&lt;\u00a00.21), mild frailty (0.21 to &lt;0.30), moderate frailty (0.30 to &lt;0.40) and severe frailty (\u22650.40). Clinical outcomes and health\u2010related quality of life were evaluated according to baseline FI along with the effect of empagliflozin on chronological changes in FI (at 12, 32 and 52\u00a0weeks).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The patient distribution was 1514 (25.3%), 2100 (35.1%), 1501 (25.1%) and 873 (14.6%) in non\u2010frail, mild frailty, moderate frailty and severe frailty, respectively. Severe frailty patients tended to be female and have low Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, more co\u2010morbidities and more polypharmacy. Incidence rates of the primary outcome of cardiovascular death or HF hospitalization increased as frailty worsened (hazard ratio [HR] of each FI category compared with the non\u2010frail group: 1.10 [95% confidence interval, CI, 0.89\u20131.35], 2.00 [1.63\u20132.47] and 2.61 [2.08\u20133.27] in the mild frailty, moderate frailty and severe frailty groups, respectively;\n                      <jats:italic>P<\/jats:italic>\n                      trend\u00a0&lt;\u00a00.001). Compared with placebo, empagliflozin reduced the risk for the primary outcome across the four FI categories, HR: 0.59 [95% CI 0.42\u20130.83], 0.79 [0.61\u20131.01], 0.77 [0.61\u20130.96] and 0.90 [0.69\u20131.16] in non\u2010frail to severe frailty categories, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      value for trend\u00a0=\u00a00.097). Empagliflozin also improved other clinical outcomes and KCCQ score across frailty categories. Compared with placebo, empagliflozin\u2010treated patients had a higher likelihood of being in a lower FI category at Weeks 12, 32 and 52 (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05), odds ratio: 1.12 [95% CI 1.01\u20131.24] at Week 12, 1.21 [1.09\u20131.34] at Week 32 and 1.20 [1.09\u20131.33] at Week 52.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Empagliflozin improved key efficacy outcomes with a possible diminution of effect in very frail patients. Empagliflozin also improved frailty status during follow\u2010up.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13393","type":"journal-article","created":{"date-parts":[[2023,12,30]],"date-time":"2023-12-30T01:04:35Z","timestamp":1703898275000},"page":"412-424","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Efficacy of empagliflozin in heart failure with preserved ejection fraction according to frailty status in EMPEROR\u2010Preserved"],"prefix":"10.1002","volume":"15","author":[{"given":"Andrew J.S.","family":"Coats","sequence":"first","affiliation":[{"name":"Heart Research Institute  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"Baylor Scott and White Research Institute  Dallas TX USA"},{"name":"University of Mississippi Medical Center  Jackson MS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tsutsui","sequence":"additional","affiliation":[{"name":"School of Medicine and Graduate School International University of Health and Welfare  Okawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram","family":"Doehner","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health Center for Regenerative Therapies (BCRT) Charit\u00e9 Universit\u00e4tsmedizin  Berlin Germany"},{"name":"Deutsches Herzzentrum der Charit\u00e9, Department of Cardiology (Campus Virchow) Charit\u00e9 Universit\u00e4tsmedizin  Berlin Germany"},{"name":"German Centre for Cardiovascular Research (DZHK) Partner Site Berlin Charit\u00e9 Universit\u00e4tsmedizin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens School of Medicine Athens University Hospital Attikon  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Cardiovascular R&amp;D Centre\u2014UnIC@RISE, Department of Physiology and Cardiothoracic Surgery Faculty of Medicine of the University of Porto  Porto Portugal"},{"name":"Department of Internal Medicine Heart Failure Clinic, Centro Hospitalar de Vila Nova de Gaia\/Espinho  Vila Nova de Gaia Portugal"},{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d'Investigation Clinique Plurith\u00e9matique 1433, U1116, CHRU de Nancy, F\u2010CRIN INI\u2010CRCT  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"B\u00f6hm","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III University Hospital Saarland, Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay K.","family":"Chopra","sequence":"additional","affiliation":[{"name":"Max Super Speciality Hospital, Saket  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subodh","family":"Verma","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery St Michael's Hospital, University of Toronto  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matias","family":"Nordaby","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH  Ingelheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Iwata","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co KG  Biberach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Nitta","sequence":"additional","affiliation":[{"name":"Medicine Division Nippon Boehringer Ingelheim Co. 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Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin Charit\u00e9 Universit\u00e4tsmedizin  Berlin Germany"},{"name":"Institute of Heart Diseases Wroclaw Medical University  Wroc\u0142aw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2006.00745.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1611"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.15420\/cfr.2021.29"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.118.005254"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.13885"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2013.07.032"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2017.01.153"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2011"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.15420\/cfr.2018.37.1"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1600827"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911303"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107038"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/db18-1152-P"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22066"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-0663"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.7326\/M21-4776"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2020.05.004"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.061754"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1596"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2318-2-1"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2318-8-24"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1832"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.06.037"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.841437"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacep.2017.06.012"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)00531-3"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000136991.85540.A9"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.057812"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S358512"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glac094"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12899"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13393","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T21:27:50Z","timestamp":1706822870000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,29]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/jcsm.13393"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13393","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,29]]},"assertion":[{"value":"2023-09-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}