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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 presents primary results from The Stabilization of Plaques Using Darapladib-TIMI 52 trial [SOLID-TIMI 52; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01000727\u0026amp;atom=%2Fspmdc%2F14%2F27%2F17.1.atom\u0022\u003ENCT01000727\u003C\/a\u003E], demonstrating that darapladib is ineffective at reducing major coronary events when started within 30 days after an acute coronary syndrome (ACS) event.\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\u003ECardiology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECoronary Artery Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECoronary Artery Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EMichelle O\u0027Donoghue, MD, Brigham and Women\u0027s Hospital, Boston, Massachusetts, USA, presented primary results from The Stabilization of Plaques Using Darapladib-TIMI 52 trial [SOLID-TIMI 52; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01000727\u0026amp;atom=%2Fspmdc%2F14%2F27%2F17.1.atom\u0022\u003ENCT01000727\u003C\/a\u003E], demonstrating that darapladib is ineffective at reducing major coronary events when started within 30 days after an acute coronary syndrome (ACS) event.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EBy way of background, lipoprotein-associated phospholipase A\u003Csub\u003E2\u003C\/sub\u003E (Lp-PLA\u003Csub\u003E2\u003C\/sub\u003E), a calcium-independent phospholipase A\u003Csub\u003E2\u003C\/sub\u003E that circulates in plasma in association with low-density lipoprotein particles, has been hypothesized to play a causal role in the development of atherosclerosis and to contribute to plaque instability through pathways related to inflammation. Darapladib is an enteric-coated, direct Lp-PLA\u003Csub\u003E2\u003C\/sub\u003E inhibitor that reduces enzyme activity in plasma and atherosclerotic plaques [Boekholdt SM et al. \u003Cem\u003ECirculation.\u003C\/em\u003E 2008].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe SOLID-TIMI 52 trial was a double-blind, placebo-controlled, phase 3 study that was conducted at 868 sites in 36 countries to compare the safety and efficacy of darapladib with placebo for patients with ACSs if started within 30 days after hospitalization. It enrolled 13 026 participants within 30 days of hospitalization with ACSs. Qualifying events were most commonly STEMI (45.2%), NSTEMI (42.7%), and unstable angina (12.2%) and were balanced between the darapladib and placebo treatment arms.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EParticipants were randomized 1:1 to darapladib (160 mg once daily; n = 6504) or matching placebo (n = 6522), with a median follow-up duration of 2.5 years. The primary end point was the composite of coronary heart disease (CHD) death, myocardial infarction (MI), or urgent coronary revascularization for myocardial ischemia. Secondary end points included the composite of cardiovascular (CV) death, MI, or stroke; total coronary events; CHD death or MI; any coronary revascularization; individual components of the primary end point; and all-cause mortality.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EAfter 3 years, the results demonstrated no significant difference in the occurrence of the primary end point between participants in the darapladib and placebo arms (16.3% vs 15.6%; HR, 1.00; 95% CI, 0.91 to 1.09; \u003Cem\u003EP\u003C\/em\u003E = .93; \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\/27\/17.1\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Occurrence of the Primary End Point in the Darapladib and Placebo Treatment Arms\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-714000394\u0022 data-figure-caption=\u0022Occurrence of the Primary End Point in the Darapladib and Placebo Treatment Arms\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\/17.1\/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\/17.1\/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\/17.1\/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\/14980\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\u003EOccurrence of the Primary End Point in the Darapladib and Placebo Treatment Arms\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003ECHD, coronary heart disease; MI, myocardial infarction.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from M. O\u0027Donoghue, 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\u003ESimilarly, darapladib did not significantly reduce the risk for the study\u0027s secondary end points of CV death, MI, or stroke (15.0% vs 15.0%; HR, 0.99; 95% CI, 0.90 to 1.09; \u003Cem\u003EP\u003C\/em\u003E = .78). Additionally, there were no significant differences between the treatment arms for the individual components of the primary end points, for additional secondary and exploratory end points, or all-cause mortality (7.3% vs 7.1%; HR, 0. 94; 95% CI, 0.82 to 1.08; \u003Cem\u003EP\u003C\/em\u003E = .40).\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EParticipants in the darapladib arm reported an odor-related complaint (predominantly of the urine, feces, and skin; 11.5% vs 2.5%) and diarrhea (10.6% vs 5.6%) more frequently than those in the placebo arm.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EThese data therefore do not support a strategy of targeted Lp-PLA\u003Csub\u003E2\u003C\/sub\u003E inhibition with darapladib on a background of optimal medical therapy in patients stabilized after ACS events, concluded Dr O\u0027Donoghue. However, ongoing trials are evaluating the clinical utility of other novel therapeutics that target alternative pathways of inflammation.\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\/17.1.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?nzou4p\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?nzou4p\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}