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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.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\u003EDarapladib, a novel inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2), may slow expansion of the necrotic core of atherosclerotic plaques in patients with acute coronary syndrome or other symptomatic coronary diseases, according to mixed results from the Integrated Biomarker and Imaging Study-2 [IBIS-2; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00268996\u0026amp;atom=%2Fspmdc%2F8%2F6%2F21.atom\u0022\u003ENCT00268996\u003C\/a\u003E].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiology clinical trials genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Elipid disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eimaging modalities\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecoronary artery disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EDarapladib, a novel inhibitor of lipoprotein-associated phospholipase A\u003Csub\u003E2\u003C\/sub\u003E (Lp-PLA\u003Csub\u003E2\u003C\/sub\u003E), may slow expansion of the necrotic core of atherosclerotic plaques in patients with acute coronary syndrome (ACS) or other symptomatic coronary diseases, according to mixed results from the Integrated Biomarker and Imaging Study-2 (IBIS-2; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00268996\u0026amp;atom=%2Fspmdc%2F8%2F6%2F21.atom\u0022\u003ENCT00268996\u003C\/a\u003E).\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003ELp-PLA\u003Csub\u003E2\u003C\/sub\u003E, an enzyme that promotes inflammation and plaque formation, is highly expressed in the necrotic core of atherosclerotic lesions. By suppressing Lp-PLA\u003Csub\u003E2\u003C\/sub\u003E, darapladib theoretically reduces endothelial inflammation and growth of the necrotic core.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EIn IBIS-2, 330 patients were randomly assigned to treatment with darapladib (n=175) or placebo (n=155) in addition to optimal medical therapy to evaluate the effects of Lp-PLA\u003Csub\u003E2\u003C\/sub\u003E inhibition on coronary plaque deformability, composition, and size. William Wijns, MD, PhD, OLV Hospital, Aalst, Belgium, reported findings from IBIS-2, which were simultaneously published online in \u003Cem\u003ECirculation\u003C\/em\u003E [Serruys PW et al. \u003Cem\u003ECirculation 2008\u003C\/em\u003E].\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ENeutral Primary Endpoint\u003C\/h2\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EInvestigators used intravascular ultrasound (IVUS) to visualize several parameters of plaque stability, including the plaque\u0027s necrotic core, dense calcium areas, and fibrous tissue. Another technique, called IVUS palpography, was used to measure the levels of tissue strain along segments of the target vessel.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EDr. Wijns and colleagues also measured high-sensitivity C-reactive protein (hsCRP) levels as a marker of systemic inflammation. The co-primary endpoints in IBIS-2 were changes in IVUS palpography and hsCRP at 12 months compared with baseline.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EAfter 1 year of treatment, the between-group difference in plaque deformability was not statistically significant (\u22120.08; p=0.22). In addition, although mean hsCRP levels declined in all patients, the mean hsCRP levels at 12 months in the placebo (1.0 mg\/L) and darapladib (0.9 mg\/L) groups were comparable (p=0.35).\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EPromising Secondary Endpoint Results\u003C\/h2\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EAlthough the IBIS-2 trial did not meet either of its co-primary endpoints, the comparison of secondary endpoints did suggest some benefit with darapladib. For example, while the volume of the necrotic core increased over 12 months in the placebo group (4.5\u00b1 17.9 mm\u003Csup\u003E3\u003C\/sup\u003E; p=0.009), plaque growth appeared to arrest in the darapladib group (\u20130.5\u00b113.9 mm\u003Csup\u003E3\u003C\/sup\u003E; p=0.71), resulting in a significant difference between the 2 treatment groups of 5.2 mm\u003Csup\u003E3\u003C\/sup\u003E, favoring darapladib (p=0.012).\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EDarapladib also had a beneficial effect on inflammatory biomarkers. As expected, patients in the darapladib group had a significant 59% reduction in Lp-PLA\u003Csub\u003E2\u003C\/sub\u003E activity compared with those in the placebo group (62 vs 153 \u03bcmol\/min\u003Csup\u003E1\u003C\/sup\u003E\/L\u003Csup\u003E1\u003C\/sup\u003E; p\u0026lt;0.001). Other inflammatory biomarkers, including oxidized phospholipid\/apolipoprotein B, did not change significantly. However, in a post hoc analysis, a higher proportion of patients in the darapladib group achieved hsCRP levels \u0026lt;1 mg\/L compared with placebo (62% vs 45%; p=0.008).\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EThe IBIS-2 trial was not powered to evaluate the effects of darapladib on cardiovascular outcomes, and no differences were observed. A safety analysis showed no differences in serious adverse events or clinical outcomes between the treatment groups, although there was a slightly higher systolic blood pressure, measured noninvasively (+3.0 mm Hg. 95% CI +0.3 to +5.7 mm Hg; p=0.031), in patients who were treated with darapladib.\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EIn summary, IBIS-2 failed to show that Lp-PLA\u003Csub\u003E2\u003C\/sub\u003E inhibition improves plaque stability, as measured by IVUS palpography. However, analyses of the IBIS-2 secondary endpoints suggest that necrotic core expansion occurs despite optimal medical therapy, even in the absence of an overall change in plaque size. In addition, treatment with darapladib appears to halt this process in patients with established coronary disease. This trial was relatively small, and patients were followed for only 12 months; thus, future clinical trials will be required to evaluate whether Lp-PLA\u003Csub\u003E2\u003C\/sub\u003E inhibition, by stopping expansion of the necrotic core, can prevent recurrent cardiovascular events in high-risk patients.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2008 MD Conference Express\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\/8\/6\/21.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_openurl.js?nzmd0d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}