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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\u003EThere are several antiplatelet agents with diverse mechanisms of action that are or will be available for treatment of the growing population of patients with cardiovascular disease. The challenge will be to understand which patients may benefit from these therapies in combination with current treatment regimens and in the context of increasingly complex patients (eg, the elderly and diabetics).\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EThrombotic Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECoronary Artery Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThere are several antiplatelet agents with diverse mechanisms of action that are or will be available for treatment of the growing population of patients with cardiovascular disease (CVD; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). The challenge, according to Robert A. Harrington, MD, Duke University, Durham, North Carolina, USA, will be to understand which patients may benefit from these therapies in combination with current treatment regimens and in the context of increasingly complex patients (eg, the elderly and diabetics). Although it is generally agreed that a personalized approach to therapy that is based on genetics and the phenotype of response is the future for selecting platelet therapy, \u201cwe are not there yet,\u201d said Dr. Harrington.\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\/11\/3\/33\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Global Burden of CVD.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1691838200\u0022 data-figure-caption=\u0022Global Burden of CVD.\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\/11\/3\/33\/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\/11\/3\/33\/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\/11\/3\/33\/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\/12269\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 \n            \u003Cp id=\u0022p-3\u0022 class=\u0022first-child\u0022\u003EGlobal Burden of CVD.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-4\u0022\u003ESince thrombosis is a key component in the pathobiology of acute CVD and because adenosine diphosphate (ADP) signaling through P2Y\u003Csub\u003E1\u003C\/sub\u003E and P2Y\u003Csub\u003E12\u003C\/sub\u003E contributes to platelet adhesion and activation [Massucato M et al. \u003Cem\u003EBlood\u003C\/em\u003E 2004], effective therapy includes blockage of the ADP receptor. Thus, ADP receptors have become the focus of much of the current research.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EElinogrel is a direct-acting, reversible P2Y\u003Csub\u003E12\u003C\/sub\u003E receptor antagonist with low potential for drug-drug interactions that produces immediate and potent inhibition of ADP-mediated platelet activation when administered intravenously (IV). This agent is also active in oral form, creating the potential for flexible dosing and transition from IV to oral administration. Data from the INNOVATE-PCI Phase 2 study (\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00751231\u0026amp;atom=%2Fspmdc%2F11%2F3%2F33.atom\u0022\u003ENCT00751231\u003C\/a\u003E) showed that in patients who were undergoing nonurgent percutaneous coronary intervention (PCI), elinogrel provided significantly greater (p\u0026lt;0.025) and faster inhibition of platelet aggregation than clopidogrel in response to platelet activation with 5 \u03bcM ADP.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ECangrelor is a direct-acting platelet P2Y\u003Csub\u003E12\u003C\/sub\u003E receptor antagonist that produces rapid platelet inhibition (\u0026gt;90%) at 4 mg\/kg\/min and has a short half-life (t\u003Csub\u003E1\/2\u003C\/sub\u003E=3 to 5 minutes). Full recovery of platelet function occurs in \u0026lt;60 minutes. Disappointing interim results led to the abandonment of the two CHAMPION clinical trials (\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00305162\u0026amp;atom=%2Fspmdc%2F11%2F3%2F33.atom\u0022\u003ENCT00305162\u003C\/a\u003E, NCT001156571) in mid-2009 [Harrington RA et al. \u003Cem\u003ENew Engl J Med\u003C\/em\u003E 2009; Bhatt DJ et al. \u003Cem\u003ENew Engl J Med\u003C\/em\u003E 2009]. However, the BRIDGE study (\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00767507\u0026amp;atom=%2Fspmdc%2F11%2F3%2F33.atom\u0022\u003ENCT00767507\u003C\/a\u003E), for short-term use prior to coronary artery bypass grafting, continues and is expected to complete in June 2013.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EVorapaxar is a protease-activated receptor 1 (PAR-1) antagonist that blocks thrombin-mediated platelet activation. In a Phase 2 study in patients who were undergoing nonurgent PCI or coronary angiography with planned PCI, oral vorapaxar did not cause an increase in TIMI bleeding, even when administered concomitantly with aspirin and clopidogrel [Becker RC et al. \u003Cem\u003ELancet\u003C\/em\u003E 2009]; however, the more recent TRACER trial (\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00527943\u0026amp;atom=%2Fspmdc%2F11%2F3%2F33.atom\u0022\u003ENCT00527943\u003C\/a\u003E), investigating the use of vorapaxar in ACS, was recently stopped early due to excessive bleeding. The TRA-2P TIMI-50 study (\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00526474\u0026amp;atom=%2Fspmdc%2F11%2F3%2F33.atom\u0022\u003ENCT00526474\u003C\/a\u003E), which is investigating vorapaxar across a broad range of stable atherosclerotic diseases, is continuing in patients with a history of myocardial infarction and peripheral vascular disease. Patients who enrolled with a history of ischemic stroke or who developed a stroke after randomization have been stopped prematurely, based on the Data Safety Monitoring Board findings in TRACER [Merck Statement on Changes to Clinical Studies of Vorapaxar January 13, 2011. Press Release].\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EThe development of potent antiplatelet agents that work through diverse mechanisms raises the concern for bleeding. Aptamers (protein-binding oligonucleotides) are reversible antagonists of coagulation factor IXa. Oligonucleotides that are complementary to these aptamers can act as antidotes to their corresponding partners and are capable of restoring platelet function quickly and effectively over a clinically relevant period, thus opening the way for the development of safer, antidote-controlled platelet inhibitors [Rusconi CP et al. \u003Cem\u003ENature\u003C\/em\u003E 2002]. Clinical studies with such aptamers are eagerly awaited.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 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\/11\/3\/33.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?nzn3mq\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?nzn3mq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}