{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:57:20Z","timestamp":1792097840702,"version":"4.4.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2019,9,17]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Evidence regarding the primary prevention of coronary artery disease events by low-density lipoprotein cholesterol (LDL-C) lowering therapy in older individuals, aged \u226575 years, is insufficient. This trial tested whether LDL-C\u2013lowering therapy with ezetimibe is useful for the primary prevention of cardiovascular events in older patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>This multicenter, prospective, randomized, open-label, blinded end-point evaluation conducted at 363 medical institutions in Japan examined the preventive efficacy of ezetimibe for patients aged \u226575 years, with elevated LDL-C without history of coronary artery disease. Patients, who all received dietary counseling, were randomly assigned (1:1) to receive ezetimibe (10 mg once daily) versus usual care with randomization stratified by site, age, sex, and baseline LDL-C. The primary outcome was a composite of sudden cardiac death, myocardial infarction, coronary revascularization, or stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Overall, 3796 patients were enrolled between May 2009 and December 2014, and 1898 each were randomly assigned to ezetimibe versus control. Median follow-up was 4.1 years. After exclusion of 182 ezetimibe patients and 203 control patients because of lack of appropriate informed consent and other protocol violations, 1716 (90.4%) and 1695 (89.3%) patients were included in the primary analysis, respectively. Ezetimibe reduced the incidence of the primary outcome (hazard ratio [HR], 0.66; 95% CI, 0.50\u20130.86;\n                      <jats:italic>P<\/jats:italic>\n                      =0.002). Regarding the secondary outcomes, the incidences of composite cardiac events (HR, 0.60; 95% CI, 0.37\u20130.98;\n                      <jats:italic>P<\/jats:italic>\n                      =0.039) and coronary revascularization (HR, 0.38; 95% CI, 0.18\u20130.79;\n                      <jats:italic>P<\/jats:italic>\n                      =0.007) were lower in the ezetimibe group than in the control group; however, there was no difference in the incidence of stroke, all-cause mortality, or adverse events between trial groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>LDL-C\u2013lowering therapy with ezetimibe prevented cardiovascular events, suggesting the importance of LDL-C lowering for primary prevention in individuals aged \u226575 years with elevated LDL-C. Given the open-label nature of the trial, its premature termination and issues with follow-up, the magnitude of benefit observed should be interpreted with caution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical 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.umin.ac.jp\">https:\/\/www.umin.ac.jp<\/jats:ext-link>\n                      . Unique identifier: UMIN000001988.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.118.039415","type":"journal-article","created":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T05:00:17Z","timestamp":1566450017000},"page":"992-1003","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":216,"title":["Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older (EWTOPIA 75)"],"prefix":"10.1161","volume":"140","author":[{"given":"Yasuyoshi","family":"Ouchi","sequence":"first","affiliation":[{"name":"Toranomon Hospital, Tokyo, Japan (Y. Ouchi, M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Sasaki","sequence":"additional","affiliation":[{"name":"International University of Health and Welfare, Fukuoka, Japan (J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Arai","sequence":"additional","affiliation":[{"name":"National Center for Geriatrics and Gerontology, Obu, Japan (H.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koutaro","family":"Yokote","sequence":"additional","affiliation":[{"name":"Chiba University, Chiba, Japan (K.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumasa","family":"Harada","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan (K.H., H.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Katayama","sequence":"additional","affiliation":[{"name":"General Tokyo Hospital, Tokyo, Japan (Y.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Urabe","sequence":"additional","affiliation":[{"name":"Juntendo University Urayasu Hospital, Urayasu, Japan (T.U.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasufumi","family":"Uchida","sequence":"additional","affiliation":[{"name":"Saga Memorial Hospital, Saga, Japan (Y.U.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Nagahama City Hospital, Nagahama, Japan (M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Yokota","sequence":"additional","affiliation":[{"name":"Yokota Clinic, Miyazaki, Japan (N.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Nishida","sequence":"additional","affiliation":[{"name":"Nishida Clinic, Neyagawa, Japan (H.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takatoshi","family":"Otonari","sequence":"additional","affiliation":[{"name":"Otonari Clinic, Chikushino, Japan (T.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Arai","sequence":"additional","affiliation":[{"name":"Arai Clinic, Yamagata, Japan (T.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Sakuma","sequence":"additional","affiliation":[{"name":"Caress Sapporo Hokko Memorial Clinic, Sapporo, Japan (I.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Sakabe","sequence":"additional","affiliation":[{"name":"Sakabe Clinic, Kyoto, Japan (K.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayasu","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Yamamoto Clinic, Shimoniikawa, Japan (M.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Jyuzen General Hospital, Niihama, Japan (T.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Oikawa","sequence":"additional","affiliation":[{"name":"Fukujuji Hospital, Tokyo, Japan (S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuya","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Rinku General Medical Center, Izumisano, Japan (S.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Rakugi","sequence":"additional","affiliation":[{"name":"Osaka University, Suita, Japan (H.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Imai","sequence":"additional","affiliation":[{"name":"Kyoto University, Japan (T.I., S.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Kyoto University, Japan (T.I., S.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Chuo University, Tokyo, Japan (Y. 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