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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 articls presented results from the Efficacy and Safety of Alirocumab (SAR236553\/REGN727) Versus Ezetimibe on Top of Statin in High Cardiovascular Risk Patients With Hypercholesterolemia trial [ODYSSEY COMBO II; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01644188\u0026amp;atom=%2Fspmdc%2F14%2F27%2F10.atom\u0022\u003ENCT01644188\u003C\/a\u003E]. This phase 3 trial showed that for patients with high cholesterol and existing or increased risk of cardiovascular disease, alirocumab significantly improved cholesterol levels as compared to ezetimibe, when added to regular statin therapy.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELipid Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELipid Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EChristopher P. Cannon, MD, Harvard Clinical Research Institute, Boston, Massachusetts, USA, presented results from the Efficacy and Safety of Alirocumab (SAR236553\/REGN727) Versus Ezetimibe on Top of Statin in High Cardiovascular Risk Patients With Hypercholesterolemia trial [ODYSSEY COMBO II; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01644188\u0026amp;atom=%2Fspmdc%2F14%2F27%2F10.atom\u0022\u003ENCT01644188\u003C\/a\u003E]. This phase 3 trial showed that for patients with high cholesterol and existing or increased risk of cardiovascular disease (CVD), alirocumab significantly improved cholesterol levels as compared to ezetimibe, when added to regular statin therapy.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EOver the last few decades, statins have been the mainstay of therapy for patients with high levels of low-density lipoprotein cholesterol (LDL-C). However, despite their significant clinical efficacy in most patients, a large residual risk remains for the development of atherosclerotic CVD [Baigent C et al. \u003Cem\u003ELancet\u003C\/em\u003E. 2010].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EProprotein convertase subtilisin kexin type 9 (PCSK9) inhibition represents a promising new strategy for the treatment of hypercholesterolemia that may complement statin therapy [Switzer MP et al. \u003Cem\u003ECardiovasc Hematol Agents Med Chem.\u003C\/em\u003E 2013]. Monoclonal antibodies (mAbs) against PCSK9 have recently been shown to be highly efficacious in lowering LDL-C, with a favorable adverse event profile in early clinical trials. Alirocumab is an investigational mAb that targets and blocks PCSK9 [Roth EM, Diller P. \u003Cem\u003EFuture Cardiol\u003C\/em\u003E. 2014].\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EODYSSEY COMBO II is a double-blind, parallel-group multicenter study being conducted over 104 weeks to evaluate the safety and efficacy of alirocumab, compared with ezetimibe, among patients (n = 720) with hypercholesterolemia who are at high cardiovascular risk and who had inadequate LDL-C control at baseline despite stable maximally tolerated statin therapy.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EInclusion criteria included either a history of CVD and LDL-C \u2265 1.81 mmol\/L (\u2265 70 mg\/dL) or no history of CVD but with other risk factors and LDL-C \u2265 2.59 mmol\/L (\u2265 100 mg\/dL) and receipt of a maximally tolerated daily statin dose (stable for \u0026gt; 4 weeks prior to screening). Exclusion criteria included receipt of other lipid-lowering therapies [Colhoun HM et al. \u003Cem\u003EBMC Cardiovasc Disord\u003C\/em\u003E. 2014].\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EPatients were randomized 2:1 to either alirocumab (75 mg, subcutaneously, Q2W; n = 479) or ezetimibe (10 mg, daily; n = 241) in addition to statin therapy. After 12 weeks, the dose of alirocumab was increased to 150 mg, Q2W, if the week 8 LDL-C level was \u2265 1.81 mmol\/L (70 mg\/dL). The primary end point was the percentage change in LDL-C from baseline to week 24.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EAt week 24, alirocumab significantly reduced LDL-C levels as compared with ezetimibe (\u201350.6% vs \u221220.7%; \u003Cem\u003EP\u003C\/em\u003E \u0026lt; .0001; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E), with a least squares mean difference versus ezetimibe of \u221229.8% (\u003Cem\u003EP\u003C\/em\u003E \u0026lt; .0001). This reduction was maintained to 52 weeks (\u201349.5% for alirocumab vs \u221218.3% for ezetimibe).\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\/27\/10\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Effect of Alirocumab and Ezetimibe on LDL-C Levels at 24 Weeks\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-780800540\u0022 data-figure-caption=\u0022Effect of Alirocumab and Ezetimibe on LDL-C Levels at 24 Weeks\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\/27\/10\/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\/27\/10\/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\/27\/10\/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\/14972\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-9\u0022 class=\u0022first-child\u0022\u003EEffect of Alirocumab and Ezetimibe on LDL-C Levels at 24 Weeks\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003ELDL-C, low-density lipoprotein cholesterol; LS, least squares (a statistical mean estimated from a linear model); SE, standard error.\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-10\u0022\u003EAt week 24, the majority of patients in the alirocumab arm were able to achieve a prespecified LDL-C target of \u0026lt; 1.81 mmol\/L (70 mg\/dL), with 77.0% and 45.6% of alirocumab and ezetimibe patients, respectively, achieving this level (\u003Cem\u003EP\u003C\/em\u003E \u0026lt; .0001). In a post hoc analysis of a lower LDL-C target of \u0026lt; 1.3 mmol\/L (50 mg\/dL), 60.3% of alirocumab versus 14.2% of ezetimibe patients, respectively, achieved this lower level.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EIn an analysis of all safety data collected until last the patient visit at week 52, alirocumab appeared to be well tolerated. Treatment-emergent adverse events (TEAEs) occurred in 71.2% patients in the alirocumab arm and 67.2% of those in the ezetimibe arm and led to discontinuation in 7.5% and 5.4% patients in each treatment arm, respectively. The most commonly reported TEAEs (occurring in \u2265 5% of patients in each treatment arm) were upper respiratory tract infection, accidental overdose, dizziness, and myalgia.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EDr Cannon summarized that, in this population of patients with high CVD risk who were unable to achieve targets with maximal statin use, a treat-to-target approach with alirocumab (where \u223c 80% of patients did not need to up-titrate the initial dose) allowed more than three-quarters of patients to achieve target LDL-C levels at week 24.\u003C\/p\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\/27\/10.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?nzotwd\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?nzotwd\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}