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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\u003EThis article discusses results from the Determining the Efficacy and Tolerability of CETP Inhibition with Anacetrapib [DEFINE; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00685776\u0026amp;atom=%2Fspmdc%2F10%2F10%2F13.atom\u0022\u003ENCT00685776\u003C\/a\u003E] trial, which showed that anacetrapib safely and substantially lowered LDL-C and raised HDL-C levels in patients with coronary heart disease.\u003C\/p\u003E\n         \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\u003Cp id=\u0022p-2\u0022\u003ECholesteryl ester transfer protein (CETP) inhibition can raise high-density lipoproteins (HDLs) and, in some cases, lower low-density lipoproteins (LDLs). Development of the first CETP agent to be evaluated in a Phase 3 clinical trial\u2014torcetrapib\u2014was stopped, however, when it was found to be associated with increased mortality and cardiovascular events [Barter PJ et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2007]. Christopher P. Cannon, MD, Brigham and Women\u0027s Hospital, Boston, Massachusetts, USA, reported results from the Determining the Efficacy and Tolerability of CETP Inhibition with Anacetrapib (DEFINE; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00685776\u0026amp;atom=%2Fspmdc%2F10%2F10%2F13.atom\u0022\u003ENCT00685776\u003C\/a\u003E) trial, which showed that anacetrapib safely and substantially lowered LDL-C and raised HDL-C levels in patients with coronary heart disease (CHD).\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EDEFINE was a Phase 2, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of anacetrapib in patients with CHD or CHD risk equivalents (Framingham Risk Score \u0026gt;20%). In addition to the CHD requirement, participants were required to be aged between 18 and 80 years and have LDL-C \u226550 but \u2264100 mg\/dL, HDL-C \u0026lt;60 mg\/dL, and triglycerides (TG) \u2264400 mg\/dL.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe primary study endpoints were the percentage change from baseline in LDL-C after 24 weeks of treatment and the safety and side effect assessments through 76 weeks. Key efficacy endpoints included HDL-C, apoB, apoA1, non-HDL-C, and TG levels at Weeks 24 and 76 and LDL-C at Week 76. Subjects (mean age 63 years, 78% men) were randomly assigned to receive 100 mg anacetrapib (n=811) or placebo (n=812) once daily for 18 months, followed by a 3-month poststudy follow-up.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EAt Week 6, LDL-C levels decreased by 40% (p\u0026lt;0.001) and HDL-C levels increased by 138% (p\u0026lt;0.001) compared with placebo (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Effects on other lipid parameters are shown in \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E. Anacetrapib did not exhibit the adverse cardiovascular effects that have been seen with torcetrapib, including changes in blood pressure, electrolyte disturbances, and elevations in aldosterone levels. Cardiovascular events occurred in 16 patients in the anacetrapib group (2.0%) and 21 patients who received placebo (2.6%; p=0.40). Using Bayesian analysis, the investigators determined that this event distribution indicated a 94% predictive probability that anacetrapib would not be associated with the 25% increase in cardiovascular adverse events that was seen with torcetrapib. Furthermore, the composite of all-cause death, MI, unstable angina, stroke, or revascularization was lower in the anacetrapib group (3.3%) compared with the placebo group (5.3%; p=0.048). This was mostly attributed to a lower rate of revascularization with anacetrapib (1.0% vs 3.5%; p\u0026lt;0.001).\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/11351\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/11351\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11351\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\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-6\u0022 class=\u0022first-child\u0022\u003EOther Lipid Parameters.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\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\/10\/10\/13\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Effects on LDL-C and HDL-C.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1992437008\u0022 data-figure-caption=\u0022Effects on LDL-C and HDL-C.\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\/10\/10\/13\/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\/10\/10\/13\/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\/10\/10\/13\/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\/11347\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 \n            \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EEffects on LDL-C and HDL-C.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003ECopyright \u00a9 2010 Massachusetts Medical Society. All rights reserved.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-9\u0022\u003E\u201cThis drug has profound effects on HDL going to new highs and with LDL going to additional lows,\u201d Dr. Cannon remarked in an interview. Additional, larger studies, soon to be initiated, are needed to establish the clinical benefit of anacetrapib, expand the ethnic diversity of the study population, and provide more insight into the long-term safety of reducing LDL-C to extremely low levels.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EThomas F. L\u00fcscher, MD, University of Zurich, Zurich, Switzerland, discussed the design and results of the DEFINE trial. He concluded the trial was well designed and that CETP inhibition with anacetrapib resulted in impressive changes in lipid profile beyond those that were achieved with statins without increasing blood pressure.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EHe further stated, however, \u201cIt remains to be shown that the HDL particles during treatment with anacetrapib are biologically normal.\u201d\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EThis article was published simultaneously in \u003Cem\u003EThe New England Journal of Medicine\u003C\/em\u003E. Cannon CP et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2010 MD Conference Express\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\/10\/10\/13.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?nzmmyp\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?nzmmyp\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_tables.js?nzmmyp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}