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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\u003Cp id=\u0022p-1\u0022\u003EA reservoir of risk in the treatment of dyslipidemia calls for optimization of statin treatment, which involves monitoring of response and compliance and adjustment of dose as needed. Also, other therapeutic approaches are needed. Niacin and fibrates are questionable options. Ezetimibe, PCSK9 inhibitors, mipomersen, and lomitapide have potential merit.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Edyslipidemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eezetimibe\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Efibrates\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Elomitapide\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Emipomersen\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eniacin\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPCSK9 inhibitors\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Estatins\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003EWhile statins are the cornerstone for lipid-lowering therapy, many patients experience major cardiovascular (CV) events despite optimal statin therapy, thereby suggesting the need for additional options for lipid-lowering therapy. Marja-Riitta Taskinen, MD, PhD, Helsinki University Hospital, Helsinki, Finland, presented some alternatives for patients for whom statins might not be the best option.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EAlternatives to statin in alleviating the risk of CV disease (CVD) include lowering of low-density lipoprotein cholesterol (LDL-C) using ezetimibe to block cholesterol absorption and using niacin or fibrates to raise the level of high-density lipoprotein cholesterol.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe future for niacin in dyslipidemia is questionable. While daily doses exceeding 1.5 g can reduce the risk of CVD events and progression of atherosclerosis, 2 large randomized clinical trials reported no clinical benefits [Boden WE et al. \u003Cem\u003ENew Engl J Med\u003C\/em\u003E. 2011; HPS2-THRIVE Collaborative Group. \u003Cem\u003ENew Engl J Med\u003C\/em\u003E. 2014]. Furthermore, niacin use has been associated with serious adverse effects [Landray M et al. \u003Cem\u003ENew Engl J Med\u003C\/em\u003E. 2014].\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EFibrates have a long history in lowering triglycerides and raising high-density lipoprotein cholesterol. Two large randomized controlled trials involving \u0026gt;\u200515\u2005000 patients with type 2 diabetes mellitus failed to demonstrate the clinical benefit of fenofibrate [ACCORD Study Group. \u003Cem\u003ENew Engl J Med\u003C\/em\u003E. 2010; Scott R et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E. 2009; FIELD Study Investigators. \u003Cem\u003ELancet\u003C\/em\u003E. 2005]. However, meta-analyses, including the FIELD and ACCORD trials, reported a benefit in reduced CVD but not all-cause or CVD-related mortality among patients with vs without dyslipidemia (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigures 1\u003C\/a\u003E and \u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003E2\u003C\/a\u003E) [Jun M et al. \u003Cem\u003ELancet\u003C\/em\u003E. 2010; Sacks FM et al. \u003Cem\u003ENew Engl J Med\u003C\/em\u003E. 2010]. Note that these results were driven by the VA-HIT and HHS trials, which did not use background intensive statin therapy.\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\/15\/28_suppl_1\/15\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Treatment Effect in Meta-Analysis of Fibrate TrialsFrom N Engl J Med, Sacks FM et al, Combination lipid therapy in type 2 diabetes, Vol 363, Pages 692-694, Copyright \u0026#xA9; (2010) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-997958951\u0022 data-figure-caption=\u0022\u0026amp;lt;div xmlns=\u0026amp;quot;http:\/\/www.w3.org\/1999\/xhtml\u0026amp;quot;\u0026amp;gt;Treatment Effect in Meta-Analysis of Fibrate TrialsFrom \u0026amp;lt;em\u0026amp;gt;N Engl J Med\u0026amp;lt;\/em\u0026amp;gt;, Sacks FM et al, Combination lipid therapy in type 2 diabetes, Vol 363, Pages 692-694, Copyright \u0026#xA9; (2010) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.\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 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/28_suppl_1\/15\/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\/28_suppl_1\/15\/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\/28_suppl_1\/15\/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\/17001\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-6\u0022 class=\u0022first-child\u0022\u003ETreatment Effect in Meta-Analysis of Fibrate Trials\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EFrom \u003Cem\u003EN Engl J Med\u003C\/em\u003E, Sacks FM et al, Combination lipid therapy in type 2 diabetes, Vol 363, Pages 692-694, Copyright \u00a9 (2010) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\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\/28_suppl_1\/15\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Meta-analysis of Fibrates in 18 TrialsReprinted from The Lancet, Vol 375, Jun M et al, Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis, Pages 1875-1884, Copyright (2010), with permission from Elsevier.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-997958951\u0022 data-figure-caption=\u0022\u0026amp;lt;div xmlns=\u0026amp;quot;http:\/\/www.w3.org\/1999\/xhtml\u0026amp;quot;\u0026amp;gt;Meta-analysis of Fibrates in 18 TrialsReprinted from \u0026amp;lt;em\u0026amp;gt;The Lancet\u0026amp;lt;\/em\u0026amp;gt;, Vol 375, Jun M et al, Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis, Pages 1875-1884, Copyright (2010), with permission from Elsevier.\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\/28_suppl_1\/15\/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\/28_suppl_1\/15\/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\/28_suppl_1\/15\/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\/17002\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-8\u0022 class=\u0022first-child\u0022\u003EMeta-analysis of Fibrates in 18 Trials\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EReprinted from \u003Cem\u003EThe Lancet\u003C\/em\u003E, Vol 375, Jun M et al, Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis, Pages 1875-1884, Copyright (2010), with permission from Elsevier.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-10\u0022\u003EThe benefit of ezetimibe added to statin therapy in \u0026gt;\u20055200 patients following acute coronary syndrome was examined in the IMPROVE-IT trial [Cannon CP et al. \u003Cem\u003ENew Engl J Med\u003C\/em\u003E. 2015]. An incremental lowering of LDL-C and improved CV outcomes were evident. The results indicate the value of drugs that lower LDL-C.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003ECurrent trials are addressing the inhibition of apolipoprotein B (apoB) as a means of regulating plasma triglyceride levels and remnant cholesterol and the use of n-3 fatty acids in patients with elevated triglycerides.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\u003Ch2 class=\u0022\u0022\u003EFuture Drug Development for Dyslipidemia\u003C\/h2\u003E\u003Cp id=\u0022p-12\u0022\u003ELessons learned in the development of mipomersen and lomitapide are instructive for future drug development in dyslipidemia, according to John Kastelein, MD, PhD, University of Amsterdam, Amsterdam, The Netherlands.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EMipomersen is an antisense nucleotide that is subcutaneously injected to inhibit the production of apoB in the liver. Mipomersen is the latest in a long line of drugs targeting apoB. Success in lowering LDL-C via apoB inhibition has been elusive. Randomized double-blind placebo-controlled trials have demonstrated the efficacy and tolerability of mipomersen in reducing LDL-C in homo- and heterozygous familial hypercholesterolemia (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E) [Raal FJ et al. \u003Cem\u003ELancet\u003C\/em\u003E. 2010; McGowan MP et al. \u003Cem\u003EPLoS ONE\u003C\/em\u003E. 2012; Stein EA et al. \u003Cem\u003ECirculation\u003C\/em\u003E. 2012].\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\/17003\/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\/17003\/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\/17003\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 \u003Cp id=\u0022p-14\u0022 class=\u0022first-child\u0022\u003EData From Phase 3 Trials of MIPO\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-19\u0022\u003ELomitapide inhibits microsomal triglyceride transfer protein in the liver and intestine, which decreases secretion of very-LDL-C into the bloodstream in clinical trial cohorts [Cuchel M et al. \u003Cem\u003ELancet\u003C\/em\u003E. 2013; Cuchel M et al. \u003Cem\u003ENew Engl J Med\u003C\/em\u003E. 2007] and individuals [Rader DJ, Kastelein JJ. \u003Cem\u003ECirculation\u003C\/em\u003E. 2014]. Adverse effects are mainly gastrointestinal and tend to wane with time, with no evidence of liver damage.\u003C\/p\u003E\u003Cp id=\u0022p-20\u0022\u003EBoth drugs have promise and may herald the subsequent development of apoB-targeted therapy.\u003C\/p\u003E\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\/28_suppl_1\/15.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?nzlg51\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?nzlg51\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?nzlg51\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}