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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\n\u003Cp id=\u0022p-1\u0022\u003EResults from IMPROVE-IT showed that adding ezetimibe to statin therapy with simvastatin significantly reduced the primary end point in moderate- to high-risk patients stabilized after acute coronary syndromes. A new analysis from IMPROVE-IT showed that the number of first and recurrent primary end point events was also reduced with combination therapy vs monotherapy over the median 6-year follow-up.\u003C\/p\u003E\n\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eezetimibe\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Esimvastatin\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Estatins\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiovascular disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EIMPROVE-IT trial\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eacute coronary syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiology \u0026amp; cardiovascular medicine clinical trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecoronary artery disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Emyocardial infarction\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n\n\u003Cp id=\u0022p-2\u0022\u003EAccording to results of a secondary analysis of the IMPROVE-IT study presented by Sabina A. Murphy, MPH, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA, adding ezetimibe to simvastatin therapy significantly improved clinical outcomes beyond a first event compared with simvastatin alone. This analysis also confirmed the importance of continuing intensive combination lipid-lowering therapy after a first cardiovascular (CV) event.\u003C\/p\u003E\n\u003Cp id=\u0022p-3\u0022\u003EEzetimibe is a nonstatin lipid-lowering therapy that reduces cholesterol absorption in the intestine. When added to a statin, achievement of low-density lipoprotein cholesterol (LDL-C) levels \u0026lt;\u200570 mg\/dL or \u0026lt;\u2005100 mg\/dL was approximately 20% higher compared with a statin alone [Morrone D et al. \u003Cem\u003EAtherosclerosis.\u003C\/em\u003E 2012]. 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%2F15%2F5%2F18.atom\u0022\u003ENCT00202878\u003C\/a\u003E] was a phase 3, multicenter, randomized, double-blind, active-control trial that evaluated whether ezetimibe added to simvastatin improved CV outcomes compared with simvastatin therapy alone.\u003C\/p\u003E\n\u003Cp id=\u0022p-4\u0022\u003EIMPROVE-IT included 18\u003Cem\u003E\u2005\u003C\/em\u003E144 moderate- to high-risk patients stabilized after acute coronary syndromes (\u2264\u200510 days) receiving standard medical and interventional therapy. Patients with a LDL-C level between 50 and 125 mg\/dL (or 50 to 100 mg\/dL if they had been taking prior lipid-lowering therapy) were randomized in a 1:1 ratio to once-daily doses of either ezetimibe\/simvastatin (10\/40 mg) or simvastatin monotherapy (40 mg) and followed for 2.5 years or until at least 5250 patients experienced a primary end point event.\u003C\/p\u003E\n\u003Cp id=\u0022p-5\u0022\u003EThe primary end point of the first occurrence of CV death, nonfatal myocardial infarction (MI), rehospitalization for unstable angina (UA), coronary revascularization (occurring \u2265\u200530 days after randomization), or stroke occurred in significantly more patients in the simvastatin monotherapy arm vs combination therapy arm (34.7% vs 32.7%; HR, 0.94; 95% CI, 0.89 to 0.99; \u003Cem\u003EP\u2005\u003C\/em\u003E=\u2005.016). The number needed to treat was 50.\u003C\/p\u003E\n\u003Cp id=\u0022p-6\u0022\u003EThe occurrence of a first event for each of the 3 prespecified secondary end points was also significantly higher with simvastatin monotherapy vs combination therapy. All-cause death\/MI\/UA\/coronary revascularization\/stroke occurred in 40.3% vs 38.7%, respectively (\u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.034). Coronary heart disease (CHD) death\/MI\/urgent coronary revascularization occurred in 18.9% vs 17.5% (\u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.016). CV death\/MI\/UA\/any revascularization\/stroke occurred in 36.2% vs 34.5% (\u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.035). Significance was driven by fewer MIs, strokes, and urgent revascularization events.\u003C\/p\u003E\n\u003Cp id=\u0022p-7\u0022\u003EThe present analysis determined the number of first and recurrent events recorded during the mean 6-year follow-up, with the hypothesis that the number of total events would be reduced with combination therapy vs simvastatin monotherapy. There were 5314 first primary end point events and 4231 additional primary end point events, the majority of which were revascularization for both first and recurrent events. Overall, there were significantly fewer total primary end point events with combination therapy (RR, 0.91; 95% CI, 0.85 to 0.97; \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.007; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). These results were reflected in a reduction in additional primary end point events (RR, 0.88; 95% CI, 0.79 to 0.98; \u003Ca id=\u0022xref-fig-1-2\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E).\u003C\/p\u003E\n\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\/5\/18\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Fewer Total (First and Recurrent) Primary End Point Events With Combination TherapyReproduced with permission from SA Murphy, MPH.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1733135469\u0022 data-figure-caption=\u0022Fewer Total (First and Recurrent) Primary End Point Events With Combination TherapyReproduced with permission from SA Murphy, MPH.\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\/5\/18\/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\/5\/18\/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\/5\/18\/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\/16199\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-8\u0022 class=\u0022first-child\u0022\u003EFewer Total (First and Recurrent) Primary End Point Events With Combination Therapy\u003C\/p\u003E\n\u003Cp id=\u0022p-9\u0022\u003EReproduced with permission from SA Murphy, MPH.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n\u003Cp id=\u0022p-10\u0022\u003EThere were fewer total secondary end point events with combination therapy as well, including fewer CHD deaths, MIs, and urgent revascularization events (RR, 0.85; 95% CI, 0.76 to 0.94; \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.002), fewer all-cause death\/MI\/UA\/coronary revascularization\/stroke (RR, 0.92; 95% CI, 0.87 to 0.98; \u003Cem\u003EP\u2005\u003C\/em\u003E=\u2005.009), and fewer CV death\/MI\/UA\/any revascularization\/stroke (RR, 0.93; 95% CI, 0.87 to 0.99; \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.02).\u003C\/p\u003E\n\u003Cp id=\u0022p-11\u0022\u003ESensitivity analysis using the Wei, Lin, and Weissfeld model for the occurrence of primary end point events favored combination therapy (model average HR, 0.93; 95% CI, 0.89 to 0.99; \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.01). The absolute risk difference for total primary end point events, nonfatal MI, and nonfatal stroke also favored ezetimibe\/simvastatin therapy (\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.05; \u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E).\u003C\/p\u003E\n\u003Cdiv id=\u0022F2\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\/5\/18\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Risk Differences for Total Primary End Point EventsCV, cardiovascular; MI, myocardial infarction; NF, nonfatal; Revasc, revascularization; UA, unstable angina.*P\u0026#x2005;\u0026amp;lt;\u0026#x2005;.05; others not significant.Reproduced with permission from SA Murphy, MPH.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1733135469\u0022 data-figure-caption=\u0022\u0026amp;lt;div xmlns=\u0026amp;quot;http:\/\/www.w3.org\/1999\/xhtml\u0026amp;quot;\u0026amp;gt;Risk Differences for Total Primary End Point EventsCV, cardiovascular; MI, myocardial infarction; NF, nonfatal; Revasc, revascularization; UA, unstable angina.*\u0026amp;lt;em\u0026amp;gt;P\u0026amp;lt;\/em\u0026amp;gt;\u0026#x2005;\u0026amp;amp;lt;\u0026#x2005;.05; others not significant.Reproduced with permission from SA Murphy, MPH.\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 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/5\/18\/F2.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\/5\/18\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\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\/5\/18\/F2.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\/16200\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\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \u003Cp id=\u0022p-12\u0022 class=\u0022first-child\u0022\u003ERisk Differences for Total Primary End Point Events\u003C\/p\u003E\n\u003Cp id=\u0022p-13\u0022\u003ECV, cardiovascular; MI, myocardial infarction; NF, nonfatal; Revasc, revascularization; UA, unstable angina.\u003C\/p\u003E\n\u003Cp id=\u0022p-14\u0022\u003E*\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.05; others not significant.\u003C\/p\u003E\n\u003Cp id=\u0022p-15\u0022\u003EReproduced with permission from SA Murphy, MPH.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n\u003Cp id=\u0022p-16\u0022\u003EThis is the first trial demonstrating clinical benefit when adding a nonstatin lipid-lowering agent to statin therapy. By treating patients with a daily combination of ezetimibe\/simvastatin rather than simvastatin alone, more than twice the number of recurrent adverse CV events was prevented compared with first events.\u003C\/p\u003E\n\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\/5\/18.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?nzlp62\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?nzlp62\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}