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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\u003EStatins have been demonstrated to reduce morbidity and mortality; however, adding other lipid-modifying therapies to statin treatment has not demonstrated a clear benefit. This article presents data from the Improved Reduction of Outcomes: Vytorin (Ezetimibe\/Simvastatin) Efficacy International Trial [IMPROVE-IT; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00202878\u0026amp;atom=%2Fspmdc%2F14%2F52%2F17.atom\u0022\u003ENCT00202878\u003C\/a\u003E]. The purpose of the IMPROVE-IT trial was to evaluate the clinical benefit of combination therapy with ezetimibe plus simvastatin compared with simvastatin monotherapy in lowering LDL-C levels.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiology clinical trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Elipid disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003ECombination therapy with ezetimibe and simvastatin reduced the rate of cardiovascular (CV) death, myocardial infarction (MI), hospital admission for unstable angina (UA), coronary revascularization, and stroke in patients with acute coronary syndrome (ACS) compared with simvastatin alone. Christopher P. Cannon, MD, Brigham and Women\u0027s Hospital, Boston, Massachusetts, USA, presented data from the Improved Reduction of Outcomes: Vytorin (Ezetimibe\/Simvastatin) Efficacy International Trial [IMPROVE-IT; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00202878\u0026amp;atom=%2Fspmdc%2F14%2F52%2F17.atom\u0022\u003ENCT00202878\u003C\/a\u003E].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EStatins have been demonstrated to reduce morbidity and mortality; however, adding other lipid-modifying therapies to statin treatment has not demonstrated a clear benefit. Ezetimibe causes decreased cholesterol absorption by inhibiting the Niemann-Pic C\u003Csub\u003E1\u003C\/sub\u003E-like\u003Csub\u003E1\u003C\/sub\u003E protein that is located primarily within the brush border of the epithelium of the gastrointestinal tract. The addition of a statin to ezetimibe therapy results in a synergistic decrease of approximately 20% in low-density lipoprotein cholesterol (LDL-C) reduction. The purpose of the IMPROVE-IT trial was to evaluate the clinical benefit of combination therapy with ezetimibe plus simvastatin compared with simvastatin monotherapy in lowering LDL-C levels The design and final baseline characteristics of the IMPROVE-IT trial were previously published [Blazing MA et al. \u003Cem\u003EAm Heart J.\u003C\/em\u003E 2014; Cannon CP et al. \u003Cem\u003EAm Heart J.\u003C\/em\u003E 2008].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn the multicenter, double-blind, phase 3 IMPROVE-IT trial, 18 144 patients with STEMI and NSTEMI, or UA who were aged \u2265 50 years were randomly assigned to receive simvastatin or ezetimibe plus simvastatin after conventional medical and interventional therapy [Blazing MA et al. \u003Cem\u003EAm Heart J.\u003C\/em\u003E 2014]. For inclusion, patients were required to have an LDL-C level of 50 to 125 mg\/dL (between 50 and 100 mg\/dL if on lipid-lowering therapy) as well as \u2265 1 high-risk feature including new ST changes, positive troponin levels, diabetes mellitus (DM), history of MI, peripheral artery disease, cerebrovascular disease, prior coronary artery bypass grafting (CABG) \u0026gt; 3 years ago, and multivessel coronary artery disease. Patients were excluded if they were undergoing CABG, their current statin therapy had potency \u0026gt; simvastatin 40 mg, their creatinine clearance was \u0026lt; 30 mL\/min, or they had active liver disease.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe primary end point of the IMPROVE-IT trial was a composite score of CV death, MI, hospital admission for UA, coronary revascularization, or stroke [Blazing MA et al. \u003Cem\u003EAm Heart J.\u003C\/em\u003E 2014]. Secondary end points included individual CV end points, as well as various composite scores. At baseline, the mean age was 64 years, 24.5% of patients were female, 27% had DM and 35.5% were on prior lipid-lowering therapy. In addition, the mean LDL-C level at the time of the ACS event was 95 mg\/dL.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ETreatment with ezetimibe plus simvastatin resulted in a greater decrease in mean LDL-C levels beginning at week 1 after randomization and remained steady up to 96 months. A significantly higher number of patients in the simvastatin monotherapy arm experienced the primary end point (34.7%) compared with patients in the ezetimibe plus simvastatin arm (34.7% vs 32.7%; HR, 0.936; 95% CI, 0.887 to 0.988; \u003Cem\u003EP\u003C\/em\u003E = .016) with a number needed to treat (NNT) of 50 (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Similarly, significantly fewer patients reached the composite of CV death, nonfatal MI, or nonfatal stroke in the ezetimibe plus simvastatin arm (20.4%) compared with the simvastatin arm (20.4% vs 22.2%; HR, 0.90; 95% CI, 0.84 to 0.97; \u003Cem\u003EP\u003C\/em\u003E = .003) with an NNT of 56. In addition, fewer patients experienced the individual end points of MI and ischemic stroke in the combination therapy arm compared with simvastatin monotherapy.\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\/14\/52\/17\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Primary End Point of the IMPROVE-IT Trial\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-2105997365\u0022 data-figure-caption=\u0022Primary End Point of the IMPROVE-IT Trial\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\/14\/52\/17\/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\/14\/52\/17\/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\/14\/52\/17\/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\/15161\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 attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EPrimary End Point of the IMPROVE-IT Trial\u003C\/p\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EIMPROVE-IT, Improved Reduction of Outcomes: Vytorin (Ezetimibe\/Simvastatin) Efficacy International Trial.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from CP Cannon, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003ESimilar rates of adverse events occurred among both arms, such as elevated liver enzymes, cholecystectomy, gallbladder-related events, rhabdomyolysis, myopathy, and cancer.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EIn conclusion, Dr Cannon stated that data from the IMPROVE-IT trial suggest that the addition of a nonstatin, LDL-C-lowering agent provides an additional clinical benefit beyond statin monotherapy. In addition, he commented that the results support the LDL hypothesis that lowering LDL-C can reduce the risk of CV events.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\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\/14\/52\/17.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?nzod01\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?nzod01\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}