{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:44:58Z","timestamp":1771461898335,"version":"3.50.1"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Patients with heart failure with reduced ejection fraction (HFrEF) and insulin-treated diabetes have a high risk of cardiovascular complications. Mineralocorticoid receptor antagonists may mitigate this risk. We aim to explore the effect of eplerenone on cardiovascular outcomes and all-cause mortality in HFrEF patients with diabetes, including those treated with insulin in the EMPHASIS-HF trial (Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>The primary outcome was the composite of heart failure hospitalization or cardiovascular death. Cox models with treatment-by-diabetes subgroup interaction terms were used.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              The median follow-up was 21 (10\u201333) months. Of the 2737 patients included, 623 (23%) had non-insulin-treated diabetes, 236 (9%) had insulin-treated diabetes and 1878 did not have diabetes. Patients with insulin-treated diabetes were younger, more often women, with higher body mass index, waist circumference, more frequent ischemic heart failure cause, impaired kidney function, and longer diabetes duration. Compared with patients without diabetes, those with insulin-treated diabetes had a 2-fold higher risk of having a primary outcome event. The hazard ratio (95% CI) for the effect of eplerenone, compared with placebo, on the primary outcome was 0.31 (0.19\u20130.50) in insulin-treated diabetes, 0.69 (0.50\u20130.93) in non-insulin-treated diabetes, and 0.72 (0.58\u20130.88) in patients without diabetes; interaction\n              <jats:italic>P<\/jats:italic>\n              =0.007. The annualized number needed-to-treat-to-benefit with regards to the primary outcome was 3 (95% CI, 3\u20134) in patients with insulin-treated diabetes, 16 (13\u201319) in patients with diabetes not receiving insulin, and 26 (24\u201328) in patients without diabetes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Patients with insulin-treated diabetes experienced a greater benefit from eplerenone than those with diabetes not treated with insulin and people without diabetes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT00232180.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.120.008075","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T18:01:22Z","timestamp":1623780082000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Impact of Insulin Treatment on the Effect of Eplerenone: Insights From the EMPHASIS-HF Trial"],"prefix":"10.1161","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct00232180","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2304-6138","authenticated-orcid":true,"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d\u2019Investigations Cliniques, - Plurith\u00e9matique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (J.P.F., Z.L., P.R., F.Z.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zohra","family":"Lamiral","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d\u2019Investigations Cliniques, - Plurith\u00e9matique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (J.P.F., Z.L., P.R., F.Z.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6317-3975","authenticated-orcid":true,"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6358-2154","authenticated-orcid":true,"given":"Karl","family":"Swedberg","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden (K.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands (D.J.v.V.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9428-7660","authenticated-orcid":true,"given":"John","family":"Vincent","sequence":"additional","affiliation":[{"name":"Pfizer, New York (J.V.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Rossignol","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d\u2019Investigations Cliniques, - Plurith\u00e9matique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (J.P.F., Z.L., P.R., F.Z.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart J.","family":"Pocock","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, London School of Hygiene and Tropical Medicine, London, United Kingdom (S.J.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Michigan, Ann Arbor (B.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-1570","authenticated-orcid":true,"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d\u2019Investigations Cliniques, - Plurith\u00e9matique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (J.P.F., Z.L., P.R., F.Z.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2017.09.001"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn153"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1116-6"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/2048872618803701"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-1574"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12412"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1201"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1146"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2018.11.022"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1535"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-150-11-200906020-00005"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-0525"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2010.04.024"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.04.086"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009492"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1400"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht247"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-004-1510-8"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.792"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2009.12.004"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-245415"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.3305\/nh.2014.30.6.7725"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2025845"}],"container-title":["Circulation: Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCHEARTFAILURE.120.008075","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T08:33:05Z","timestamp":1738830785000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCHEARTFAILURE.120.008075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":24,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1161\/CIRCHEARTFAILURE.120.008075"],"URL":"https:\/\/doi.org\/10.1161\/circheartfailure.120.008075","relation":{},"ISSN":["1941-3289","1941-3297"],"issn-type":[{"value":"1941-3289","type":"print"},{"value":"1941-3297","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6]]},"assertion":[{"value":"2020-10-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e008075"}}