{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T13:37:39Z","timestamp":1769089059493,"version":"3.49.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":3842,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T00:00:00Z","timestamp":1436832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81200101"],"award-info":[{"award-number":["81200101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81200101"],"award-info":[{"award-number":["81200101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The optimal dosing strategies for blocking the renin-angiotensin-aldosterone system in idiopathic dilated cardiomyopathy (IDCM) are poorly known. We sought to determine the long-term efficacy and safety of supramaximal titration of benazepril and valsartan in patients with IDCM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>480 patients with IDCM in New York Heart Association functional class II\u2013IV and with left ventricular ejection fraction \u226435% were randomly assigned to extended-release metoprolol (mean 152 mg\/day, range 23.75\u2013190), low-dose benazepril (20 mg\/day), low-dose valsartan (160 mg\/day), high-dose benazepril (mean 69 mg\/day, range 40\u201380), and high-dose valsartan (mean 526 mg\/day, range 320\u2013640). After a median follow-up of 4.2 years, high-dose benazepril and valsartan, compared with their respective low dosages, resulted in 41% and 52% risk reduction in the primary endpoint of all-cause death or admission for heart failure (P = 0.042 and 0.002), promoted functional improvement, and reversed remodelling as assessed by New York Heart Association classes, quality-of-life scores, and echocardiographic recording of left ventricular ejection fraction, left ventricular end-diastolic volume, mitral regurgitation, and wall motion score index. Compared with metoprolol, high-dose valsartan reduced risk for the primary endpoint by 46% (P = 0.006), whereas high-dose benazepril and both low-dose groups showed no significant difference. Major adverse events involved hypotension and renal impairment but were largely tolerated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Supramaximal doses of benazepril and valsartan were well tolerated and produced extra benefit than their low dosages in clinical outcome and cardiac reverse remodelling in patients with IDCM and modest-severe heart failure. ClinicalTrials.gov identifier: NCT01917149.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.12042","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T11:00:26Z","timestamp":1436871626000},"page":"129-138","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Efficacy and Safety of Supramaximal Titrated Inhibition of Renin-Angiotensin-Aldosterone System in Idiopathic Dilated Cardiomyopathy"],"prefix":"10.1093","volume":"2","author":[{"given":"Zheng","family":"He","sequence":"first","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Xijing Hospital, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihua","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongli","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anlin","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronghua","family":"Luan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Statistics, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiujun","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,7,14]]},"reference":[{"key":"2026012115143259900_ehf212042-bib-0001","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1161\/CIRCULATIONAHA.106.174287","article-title":"Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; 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