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{\u0022basePath\u0022:\u0022\\\/\u0022,\u0022pathPrefix\u0022:\u0022\u0022,\u0022highwire\u0022:{\u0022markup\u0022:[{\u0022requested\u0022:\u0022full-text\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;14\\\/52\\\/16\u0022},{\u0022requested\u0022:\u0022long\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;14\\\/52\\\/16\u0022}],\u0022ac\u0022:{\u0022spmdc;14\\\/52\\\/16\u0022:{\u0022access\u0022:{\u0022reprint\u0022:true,\u0022full\u0022:true},\u0022pisa_id\u0022:\u0022spmdc;14\\\/52\\\/16\u0022,\u0022atom_uri\u0022:\u0022\u0022,\u0022jcode\u0022:\u0022spmdc\u0022}}},\u0022googleanalytics\u0022:{\u0022trackOutbound\u0022:1,\u0022trackMailto\u0022:1,\u0022trackDownload\u0022:1,\u0022trackDownloadExtensions\u0022:\u00227z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip\u0022,\u0022trackUrlFragments\u0022:1},\u0022ajaxPageState\u0022:{\u0022js\u0022:{\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/jquery.cluetip.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.hoverIntent.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.bgiframe.min.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_at_symbol.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_article_reference_popup.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/contrib\\\/google_analytics\\\/googleanalytics.js\u0022:1,\u00220\u0022:1}}});\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Clink 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\u003EIn clinical practice, up to 25% of patients are statin intolerant as a result of symptoms and abnormalities in biomarkers. This article discusses results from the Study of Alirocumab (REGN727\/SAR236553) in Patients With Primary Hypercholesterolemia and Moderate, High, or Very High Cardiovascular Risk, Who Are Intolerant to Statins [Odyssey Alternative; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01709513\u0026amp;atom=%2Fspmdc%2F14%2F52%2F16.atom\u0022\u003ENCT01709513\u003C\/a\u003E]. These trials compared statin intolerant patients who were treated with alirocumab versus ezetimibe.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EODYSSEY\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\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003ETreatment of patients who are statin intolerant with alirocumab resulted in a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) when compared with ezetimibe. Patrick M. Moriarty, MD, University of Kansas Medical Center, Kansas City, Kansas, USA, presented these results from the Study of Alirocumab (REGN727\/SAR236553) in Patients With Primary Hypercholesterolemia and Moderate, High, or Very High Cardiovascular Risk, Who Are Intolerant to Statins [Odyssey Alternative; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01709513\u0026amp;atom=%2Fspmdc%2F14%2F52%2F16.atom\u0022\u003ENCT01709513\u003C\/a\u003E].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EIn clinical practice, up to 25% of patients are statin intolerant as a result of symptoms and abnormalities in biomarkers [Mancini GB et al. \u003Cem\u003ECan J Cardiol.\u003C\/em\u003E 2013; Cohen JD et al. \u003Cem\u003EJ Clin Lipidol.\u003C\/em\u003E 2012; Bruckert E et al. \u003Cem\u003ECardiovasc Drugs Ther.\u003C\/em\u003E 2005]. However, evidence from well-designed randomized trials is lacking for alternative cholesterol-lowering agents [Guyton JR et al. \u003Cem\u003EJ Clin Lipidol.\u003C\/em\u003E 2014]. The purpose of the Odyssey Alternative trial was to evaluate the efficacy and safety of the monoclonal antibody alirocumab in patients intolerant of statins.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn the double-blind phase 3 trial, 314 patients with statin intolerance were randomly assigned to receive alirocumab, ezetimibe, or atorvastatin for 24 weeks, followed by 2 years of open-label alirocumab treatment. Statin intolerance was defined as intolerance caused by muscle-related symptoms to a minimum of 2 statin drugs, including 1 at the lowest recommended dosage. All patients received placebo for 4 weeks before randomization. This was 1 of 3 periods of validation for these patients to determine their true intolerance to statins. During this period, 13% of patients dropped out, a majority because of muscle complaints. The patients who finished that section then were randomized into the blinded 24-week therapy section. These patients were blinded to alirocumab, ezetimibe, or atorvastatin for further validation of their intolerance to stains. At week 12, the dose of the study drug was increased if the LDL-C was \u2265 70 or \u2265 100 mg\/dL, according to cardiovascular risk. The primary end point was percentage change in LDL-C from baseline in the alirocumab and ezetimibe arms.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EAt baseline, the mean age among all 3 cohorts was 63 years; slightly more than half were men; mean body mass index ranged from 28 to 30 kg\/m\u003Csup\u003E2\u003C\/sup\u003E; and 7% of patients were current smokers. Hypertension was present in 62% of the patients, type 2 DM in 24%, and chronic heart disease in 46%. The mean LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides were 191, 50, and 154 mg\/dL, respectively.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EIn the intention-to-treat population, patients who received alirocumab experienced a significantly greater decrease in LDL-C from baseline at week 24 as compared with patients who received ezetimibe (\u221245% vs \u221214.6%; \u003Cem\u003EP\u003C\/em\u003E \u0026lt; .0001). The decrease in LDL-C occurred within 4 weeks of treatment and remained steady over the study period (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). In addition, 42% of patients achieved their LDL-C goal by week 24, compared with 4% in the ezetimibe arm (\u003Cem\u003EP\u003C\/em\u003E \u0026lt;.0001). Other lipids\u2014including non-HDL-C, apolipoprotein B, and lipoprotein (a)\u2014demonstrated a greater reduction from baseline in the alirocumab arm versus the ezetimibe arm.\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\/16\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Effect of Alirocumab and Ezetimibe on Low-Density Lipoprotein Cholesterol Over 24 Weeks\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-42414203\u0022 data-figure-caption=\u0022Effect of Alirocumab and Ezetimibe on Low-Density Lipoprotein Cholesterol Over 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\/52\/16\/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\/16\/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\/16\/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\/15200\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\u003EEffect of Alirocumab and Ezetimibe on Low-Density Lipoprotein Cholesterol Over 24 Weeks\u003C\/p\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003ELDL-C, low-density lipoprotein cholesterol; Q2W, every other week.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from PM Moriarty, 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\u003EIn the safety analysis, a similar number of patients experienced treatment-emergent adverse events (TEAEs), with 18%, 25%, and 25% discontinuing alirocumab, ezetimibe, and atorvastatin, respectively, because of TEAEs. The number of skeletal muscle TEAEs was significantly different between the alirocumab and atorvastatin arms, (\u003Cem\u003EP\u003C\/em\u003E \u0026lt; .042) but total discontinuation occurred in 19% of patients, with a similar number occurring in all 3 arms of the study. Common adverse events included myalgia, nasopharyngitis, arthralgia, upper respiratory tract infection, headache, fatigue, muscle spasms, back pain, paresthesia, vomiting, and muscular weakness. The 14-week interim analysis of the open label alirocumab period has indicated that \u0026lt;3% of the patients have dropped out because of TEAEs.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EDr Moriarty concluded that the data from the Odyssey Alternative trial indicate that alirocumab had greater efficacy than ezetimibe at week 24 for the reduction of LDL-C, with fewer TEAEs, including fewer skeletal muscle events. Additionally, the unpredictable nature of patients\u0027 intolerance to alirocumab, ezetimibe, and atorvastatin in the 4-week placebo period and 24-week blinded therapy period demonstrates the complexity of diagnosing and treating patients with statin intolerance.\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\/16.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?nzocrp\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?nzocrp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}