{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T22:56:45Z","timestamp":1782514605910,"version":"3.54.5"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">IMPROVE<\/jats:styled-content>\n              \u2010\n              <jats:styled-content style=\"fixed-case\">IT<\/jats:styled-content>\n              (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) showed that adding the nonstatin ezetimibe to statin therapy further reduced cardiovascular events in patients after an acute coronary syndrome. In a prespecified analysis, we explore results stratified by sex.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In\n              <jats:styled-content style=\"fixed-case\">IMPROVE<\/jats:styled-content>\n              \u2010\n              <jats:styled-content style=\"fixed-case\">IT<\/jats:styled-content>\n              , patients with acute coronary syndrome and low\u2010density lipoprotein cholesterol of 50 to 125\u00a0mg\/dL were randomized to placebo\/simvastatin 40\u00a0mg or ezetimibe\/simvastatin 10\/40\u00a0mg. They were followed up for a median of 6\u00a0years for the primary composite of cardiovascular death, myocardial infarction, hospitalization for unstable angina, coronary revascularization \u226530\u00a0days, and stroke. Among 18\u00a0144 patients in\n              <jats:styled-content style=\"fixed-case\">IMPROVE<\/jats:styled-content>\n              \u2010\n              <jats:styled-content style=\"fixed-case\">IT<\/jats:styled-content>\n              , 4416 (24%) were women. At 12\u00a0months, the addition of ezetimibe to simvastatin significantly reduced low\u2010density lipoprotein cholesterol from baseline compared with simvastatin monotherapy in men and women equally (absolute reduction, 16.7\u00a0mg\/dL in men and 16.4\u00a0mg\/dL in women). Women receiving ezetimibe\/simvastatin had a 12% risk reduction over those receiving placebo\/simvastatin for the primary composite end point (hazard ratio, 0.88; 95% confidence interval, 0.79\u20130.99) compared with a 5% reduction for men (hazard ratio, 0.95; 95% confidence interval, 0.90\u20131.01;\n              <jats:italic>P<\/jats:italic>\n              =0.26 for interaction). When the total number of primary events was considered, women had an 18% reduction with the addition of ezetimibe (relative risk, 95% confidence interval, 0.81; 0.71\u20130.94) and men had a 6% reduction (relative risk, 0.94; 95% confidence interval, 0.87\u20131.02;\n              <jats:italic>P<\/jats:italic>\n              =0.08 for interaction). The addition of ezetimibe did not increase the rates of safety events in either women or men.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">IMPROVE<\/jats:styled-content>\n              \u2010\n              <jats:styled-content style=\"fixed-case\">IT<\/jats:styled-content>\n              demonstrated that the benefit of adding ezetimibe to statin is present in both women and men, with a good safety profile supporting the use of intensive, combination, lipid\u2010lowering therapy to optimize cardiovascular outcomes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Clinical Trial Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">URL<\/jats:styled-content>\n              :\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier:\n              <jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>\n              00202878.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.006901","type":"journal-article","created":{"date-parts":[[2017,11,19]],"date-time":"2017-11-19T01:10:12Z","timestamp":1511053812000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":55,"title":["Efficacy and Safety of Adding Ezetimibe to Statin Therapy Among Women and Men: Insight From IMPROVE\u2010IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)"],"prefix":"10.1161","volume":"6","author":[{"given":"Eri Toda","family":"Kato","sequence":"first","affiliation":[{"name":"Kyoto University Hospital, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Cannon","sequence":"additional","affiliation":[{"name":"TIMI (Thrombolysis in Myocardial Infarction) Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Blazing","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Bohula","sequence":"additional","affiliation":[{"name":"TIMI (Thrombolysis in Myocardial Infarction) Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sema","family":"Guneri","sequence":"additional","affiliation":[{"name":"Dokuz Eylul University, Izmir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"White","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina A.","family":"Murphy","sequence":"additional","affiliation":[{"name":"TIMI (Thrombolysis in Myocardial Infarction) Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong\u2010Gun","family":"Park","sequence":"additional","affiliation":[{"name":"TIMI (Thrombolysis in Myocardial Infarction) Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Braunwald","sequence":"additional","affiliation":[{"name":"TIMI (Thrombolysis in Myocardial Infarction) Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert 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