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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\u003Cp id=\u0022p-1\u0022\u003EThe IMPROVE-IT trial showed that the cholesterol-lowering drug ezetimibe, when added to simvastatin, provides greater improvement in cardiovascular outcomes among patients with diabetes vs those without diabetes in a population with acute coronary syndrome. Additionally, the rate of new-onset diabetes was not increased among patients treated with ezetimibe.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eacute coronary syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiovascular risk\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Echolesterol\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ediabetes mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eezetimibe\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EIMPROVE-IT\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Esimvastatin\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003EThe IMPROVE-IT trial showed that the cholesterol absorption inhibitor ezetimibe, when added to statin therapy, reduced cardiovascular events in patients with acute coronary syndrome (ACS) [Cannon CP et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2015]. Among patients with diabetes, ezetimibe has been shown to reduce the levels of low-density lipoprotein cholesterol (LDL-C) and other lipids, and lower insulin resistance. Data from 2 meta-analyses suggested that intensive-dose statin therapy can increase the risk of new-onset diabetes mellitus (NODM) [Preiss D et al. \u003Cem\u003EJAMA\u003C\/em\u003E. 2011; Sattar N et al. \u003Cem\u003ELancet\u003C\/em\u003E. 2010]. A pooled analysis comparing simvastatin alone vs ezetimibe plus simvastatin in patients without diabetes found both arms had small but significant increases in fasting glucose but there were no between-group differences [Toth P et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E. 2015].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EIn the IMPROVE-IT trial, a total of 18\u2005144 patients stabilized after ACS \u2264\u200510 days were randomized to ezetimibe 10 mg plus simvastatin 40 mg vs placebo plus simvastatin 40 mg for a minimum 2.5 years. A recent analysis of this trial, presented by Robert P. Giugliano, MD, SM, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA, examined the effects of ezetimibe vs placebo in a prespecified subgroup of patients with diabetes (n\u2005=\u20054933) vs patients without diabetes (n\u2005=\u200513\u2005202). The primary end point was the composite of cardiovascular death, myocardial infarction (MI), documented unstable angina (UA) requiring rehospitalization, coronary revascularization (\u2265\u200530 days), or stroke.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe intention-to-treat results demonstrated a significantly lower risk for the primary end point among patients with diabetes treated with ezetimibe plus simvastatin vs placebo plus simvastatin (40% vs 46%; HR, 0.86; 95% CI, 0.78 to 0.94) after 7 years (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Among patients without diabetes, there was no significant difference in the primary end point between the treatment groups. Patients with diabetes had a significantly greater benefit from ezetimibe than those without diabetes (\u003Cem\u003EP\u003C\/em\u003E\u003Csub\u003EInt\u2005\u003C\/sub\u003E=\u2005.023).\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/28\/21\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Primary Composite End Point at 7 Years After Randomization (Intention-to-Treat)Cardiovascular death, myocardial infarction, documented unstable angina requiring rehospitalization, coronary revascularization (\u0026#x2265;\u0026#x2005;30 d), or stroke.DM, diabetes mellitus; EZE, ezetimibe; KM, Kaplan-Meier; plac, placebo; simva, simvastatin.*Pint\u0026#x2005;=\u0026#x2005;.023.Reproduced with permission from RP Giugliano, MD\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1559280527\u0022 data-figure-caption=\u0022\u0026amp;lt;div xmlns=\u0026amp;quot;http:\/\/www.w3.org\/1999\/xhtml\u0026amp;quot;\u0026amp;gt;Primary Composite End Point at 7 Years After Randomization (Intention-to-Treat)Cardiovascular death, myocardial infarction, documented unstable angina requiring rehospitalization, coronary revascularization (\u0026#x2265;\u0026#x2005;30 d), or stroke.DM, diabetes mellitus; EZE, ezetimibe; KM, Kaplan-Meier; plac, placebo; simva, simvastatin.*\u0026amp;lt;em\u0026amp;gt;P\u0026amp;lt;\/em\u0026amp;gt;\u0026amp;lt;sub\u0026amp;gt;int\u0026amp;lt;\/sub\u0026amp;gt;\u0026#x2005;=\u0026#x2005;.023.Reproduced with permission from RP Giugliano, MD\u0026amp;lt;\/div\u0026amp;gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/28\/21\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/28\/21\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/28\/21\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16978\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \u003Cp id=\u0022p-5\u0022 class=\u0022first-child\u0022\u003EPrimary Composite End Point at 7 Years After Randomization (Intention-to-Treat)\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ECardiovascular death, myocardial infarction, documented unstable angina requiring rehospitalization, coronary revascularization (\u2265\u200530 d), or stroke.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EDM, diabetes mellitus; EZE, ezetimibe; KM, Kaplan-Meier; plac, placebo; simva, simvastatin.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003E*\u003Cem\u003EP\u003C\/em\u003E\u003Csub\u003Eint\u003C\/sub\u003E\u2005=\u2005.023.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EReproduced with permission from RP Giugliano, MD\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-10\u0022\u003EAnalysis of the individual cardiovascular end points in patients with diabetes treated with ezetimibe showed a significant reduction in MI (24% reduction, \u003Cem\u003EP\u003C\/em\u003E\u003Csub\u003EInt\u003C\/sub\u003E\u2005=\u2005.028) and ischemic stroke (39% reduction, \u003Cem\u003EP\u003Csub\u003EInt\u003C\/sub\u003E\u003C\/em\u003E\u2005=\u2005.031) but not in cardiovascular death (\u003Cem\u003EP\u003C\/em\u003E\u003Csub\u003EInt\u003C\/sub\u003E\u2005=\u2005.57), when compared with patients without diabetes who were treated with ezetimibe. There was no significant difference in the safety profile of ezetimibe when stratified by the presence of diabetes.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EThe IMPROVE-IT trial investigators also analyzed the occurrence of NODM among patients treated with ezetimibe. The results were presented by Michael A. Blazing, MD, Duke Clinical Research Institute, Durham, North Carolina, USA. NODM was defined as the initiation of diabetes medication or 2 consecutive fasting glucose levels \u2265\u20057 mmol\/L. Patients with pre-existing diabetes were excluded from the analysis population. Pre-existing diabetes was defined as use of a hypoglycemic drug or elevated glucose at randomization (fasting glucose \u2265\u20057 mmol\/L or nonfasting glucose \u2265\u200511.1 mmol\/L).\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EAfter a mean follow-up of 75 months, a total of 1414 (13.3%) patients were diagnosed with NODM. The risk of NODM was similar between the 2 treatment arms, with 720 patients developing NODM in the ezetimibe plus simvastatin group compared with 694 in the placebo plus simvastatin group (HR, 1.04; 95% CI, 0.94 to 1.15; \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.46).\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EA breakdown of the primary outcome by the defining criteria for NODM showed similar percentages of NODM in the 2 treatment groups. A sensitivity analysis using 4 alternate NODM definitions and an alternate exclusion definition for prior diabetes was performed. The alternate definitions were as follows: (1) initiation of a hypoglycemic drug; (2) 2 consecutive fasting glucose levels \u2265\u20057 mmol\/L; (3) diabetes-related adverse event reporting; and (4) either no. 1 or 3. The alternate definition for diabetes exclusion at randomization included investigator-reported diabetes in the case report form. These analyses found no significant difference in the numbers of NODM in the ezetimibe plus simvastatin vs the simvastatin groups using any of the alternate definitions.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EThese analyses of the IMPROVE-IT trial provide new information on the effects of ezetimibe on patients with diabetes and the potential for risk of NODM with the use of ezetimibe. The first analysis showed that patients with diabetes had a higher risk for cardiovascular events than patients without diabetes. This translated to a greater relative and absolute benefit from the addition of ezetimibe to simvastatin in patients with diabetes as compared with patients without diabetes. The increased benefit in patients with diabetes was driven by reductions in MI and ischemic stroke. The safety profile of ezetimibe plus simvastatin was similar to that of placebo plus simvastatin in both diabetes and nondiabetes groups. The second analysis showed that the rates of NODM at 75 months\u2019 follow-up were similar in the groups treated with simvastatin plus ezetimibe and simvastatin plus placebo.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/15\/28\/21.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzl4sp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzl4sp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}