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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\u003EApproximately 10% to 20% of patients treated with statins experience side effects, primarily musculoskeletal side effects, which diminish compliance or cause discontinuation of therapy [Zhang H et al. \u003Cem\u003EAnn Intern Med\u003C\/em\u003E 2013; Mancini GB et al \u003Cem\u003ECan J Cardiol\u003C\/em\u003E 2011]. Evolocumab, a fully human monoclonal antibody that binds proprotein convertase subtilisin\/kexin type 9 (PCSK9), reduced levels of low-density lipoprotein cholesterol (LDL-C) to a greater extent than ezetimibe in hypercholesterolemic patients who could not tolerate effective doses of statins. This article presents the results from a double-blind multicenter Phase 3 Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin-Intolerant Subjects 2 study [GAUSS-2; Stroes E et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2014].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\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\u003ELipid Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EApproximately 10% to 20% of patients treated with statins experience side effects, primarily musculoskeletal side effects, which diminish compliance or cause discontinuation of therapy [Zhang H et al. \u003Cem\u003EAnn Intern Med\u003C\/em\u003E 2013; Mancini GB et al \u003Cem\u003ECan J Cardiol\u003C\/em\u003E 2011]. Reduced adherence to, and discontinuation of, statins adversely affect survival in both the primary and secondary prevention settings [Chowdhury R et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2013; Perreault S et al. \u003Cem\u003EEur J Clin Pharmacol\u003C\/em\u003E 2009; Rasmussen JN et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2007]. Further therapeutic efforts are therefore needed to lower low-density lipoprotein cholesterol (LDL-C) in this setting. Evolocumab, a fully human monoclonal antibody that binds proprotein convertase subtilisin\/kexin type 9 (PCSK9), reduced levels of low-density lipoprotein cholesterol (LDL-C) to a greater extent than ezetimibe in hypercholesterolemic patients who could not tolerate effective doses of statins.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EErik Stroes, MD, Academic Medical Center, Amsterdam, The Netherlands, presented the results from a double-blind multicenter Phase 3 Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin-Intolerant Subjects 2 study [GAUSS-2; Stroes E et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2014] in which 307 patients with hypercholesterolemia who were statin intolerant were randomized on a 2:2:1:1 basis to evolocumab, 140 mg Q2W or 420 mg QM plus daily oral placebo, or subcutaneous placebo (Q2W or QM) plus 100 mg\/day of oral ezetimibe. The study was designed to build on the Phase 2 experience with evolocumab, which demonstrated potent LDL-C lowering in hypercholesterolemic patients intolerant to at least one statin [Sullivan D et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EParticipants qualified for the study if they were unable to tolerate effective doses of \u22652 statins because of myalgia, myopathy, myositis, or rhabdomyolysis that resolved with statin discontinuation [Stroes E et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2014]. Their mean LDL-C at baseline was \u223c195 mg\/dL. The coprimary endpoints were the mean percent change from baseline in LDL-C at Week 12 and the mean at Weeks 10 and 12.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EMean age of patients ranged from 60 to 63 years in the four treatment groups. More than 90% were white and the distribution between males and females was fairly equal. About 60% of patients qualified as high risk under the National Cholesterol Education Program risk category system. An additional 15% were classified as moderate risk. More than half of the patients were intolerant to at least three statins. Seventy eight percent to 88% had myalgia as their worst muscle-related side effect to statins.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ECompared with ezetimibe, patients randomized to evolocumab Q2W had a 37% reduction in LDL-C at a mean of 10 and 12 weeks, and a 38% reduction at 12 weeks. Patients randomized to monthly evolocumab had a 39% reduction in LDL-C at a mean of 10 and 12 weeks and a 38% reduction at 12 weeks as compared with ezetimibe (p\u0026lt;0.001 for all comparisons). Compared with baseline, the mean reductions in LDL-C at 12 weeks were 56% with Q2W evolocumab and 53% with monthly dosing. Of evolocumab-treated patients at high risk, \u0026gt;75% achieved LDL-C \u0026lt;100 mg\/dL compared with \u0026lt;10% of ezetimibe-treated patients (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E).\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\/4\/17\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022LDL-C Goal Achievement at Week 12\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1533726402\u0022 data-figure-caption=\u0022LDL-C Goal Achievement at Week 12\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\/4\/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\/4\/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\/4\/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\/15819\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-7\u0022 class=\u0022first-child\u0022\u003ELDL-C Goal Achievement at Week 12\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003ELDL-C=low-density lipoprotein cholesterol.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced from Stroes E et al. Anti-PCSK9 Antibody Effectively Lowers Cholesterol in Patients with Statin Intolerance: The GAUSS-2 Randomized, Placebo-controlled Phase 3 Clinical Trial of Evolocumab. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2014 doi: 10.1016\/j.jacc.2014.03.019. With permission from Elsevier.\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\u003EBoth dosing frequencies of evolocumab also significantly reduced levels of apolipoprotein B and lipoprotein (a) and increased levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EThe rate of adverse events was generally balanced across treatment groups. The most common adverse events (\u0026gt;5% in evolocumab combined group) were headache (8% with evolocumab vs 9% with ezetimibe), myalgia (8% vs 18%), pain in extremity (7% vs 1%), and muscle spasms (6% vs 4%).\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EDr. Stroes noted that the robust LDL-C lowering and good tolerability suggests that evolocumab is a promising therapy for high-risk hypercholesterolemic patients.\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\/4\/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?nzpbq2\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?nzpbq2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}