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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\u003EAntiplatelet therapy with aspirin and\/or clopidogrel remains a crucial treatment for patients with various forms of atherosclerosis. Neither therapy is ideal, however, because patients may be resistant to therapy and experience breakthrough events.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ELipid Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EThrombotic Disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EWhere Are We in 2010?\u003C\/h2\u003E\n         \u003Cp id=\u0022p-2\u0022\u003EAntiplatelet therapy with aspirin and\/or clopidogrel remains a crucial treatment for patients with various forms of atherosclerosis. Neither therapy is ideal, however, because patients may be resistant to therapy and experience breakthrough events, said Jeffrey I. Weitz, MD, McMaster University, Ontario, Canada. This has been demonstrated more clearly for clopidogrel, for which the resistance is related, at least in part, to CYP2C19 loss-of-function mutations, which attenuate clopidogrel activation in the liver. These mutations appear to be associated with reduced clinical effect (cardiovascular [CV] death, myocardial infarction [MI], and stroke) in patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI), but they may be less important in patients who are managed medically [Mega JL et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009; Wallentin L et al. \u003Cem\u003ELancet\u003C\/em\u003E 2010; Par\u00e9 G et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EOne option for clopidogrel-resistant patients who undergo PCI is to increase the dose of clopidogrel. This hypothesis was tested in the CURRENT-OASIS 7 trial, which showed no benefit with double-dose versus standard-dose clopidogrel in patients with ACS (HR, 0.94; 95% CI, 0.83 to 1.06; p=0.30) [The CURRENT-OASIS 7 investigators. \u003Cem\u003ENEJM\u003C\/em\u003E 2010]. However, in a subsequent post hoc subgroup analysis, double-dose clopidogrel was associated with reductions in the composite rate of CV death, MI, or stroke (HR, 0.86; 95% CI, 0.75 to 0.99; p=0.039) and in definite stent thrombosis (HR, 0.54; 95% CI, 0.39 to 0.74; p=0.0001) in patients who underwent PCI [Mehta SR et al. \u003Cem\u003ELancet\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EA second option is to choose a more potent adenosine diphosphate (ADP) receptor antagonist, such as prasugrel and ticagrelor, both of which have shown significant benefits in reducing vascular events compared with clopidogrel [Wiviott SD et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2007; Wallentin L et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009]. Although greater ADP receptor blockade improves outcomes, it also carries a higher risk of bleeding.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EAdditional approaches include genotyping and measuring platelet reactivity. Yet, the recently released results of the Gauging Responsiveness With a VerifyNow Assay\u2014Impact on Thrombosis and Safety (GRAVITAS) trial showed no significant benefit in cardiovascular outcomes when the clopidogrel dose was doubled in patients with high residual platelet activity after PCI [Price M et al. AHA 2010 Chicago].\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003ESafer, more effective antiplatelet therapies are needed, Dr. Weitz concluded. Although several of the newer compounds that are under investigation are being evaluated as add-on therapy, he noted, it may be time to focus on a replacement approach instead of ascertaining whether agents, such as prasugrel, ticagrelor, and protease-activated receptor 1 (PAR-1) inhibitors, can replace existing agents without sacrificing safety.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EBeyond 2010: The Future of Antithrombotic Therapy\u003C\/h2\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EDespite an extensive list of antithrombotic therapies that are available or under development, treating patients with acute and chronic coronary conditions that are related to thrombosis has become more challenging, said Robert A. Harrington, MD, Duke Clinical Research Institute, Durham, North Carolina, USA. Recent data from the ACTION Registry-Get With the Guidelines, for instance, showed that patients today are older and have more comorbidities (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E), making them an increasingly complex population to treat.\u003C\/p\u003E\n         \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\/11421\/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\/11421\/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\/11421\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 \n               \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EComorbidities Among Patients with CAD: Baseline Characteristics\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-9\u0022\u003ERather than taking a one-size-fits-all approach to prevent thrombosis, Dr. Harrington said, clinicians will need to consider several factors when choosing antithrombotic therapy, including:\u003C\/p\u003E\n         \u003Cul class=\u0022list-unord \u0022 id=\u0022list-1\u0022\u003E\u003Cli id=\u0022list-item-1\u0022\u003E\n               \u003Cp id=\u0022p-10\u0022\u003EClinical setting\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-2\u0022\u003E\n               \u003Cp id=\u0022p-11\u0022\u003EIndividual characteristics of each patient, including, importantly, whether or not a patient has adequate social support and financial means to be able to adhere to long-term therapy\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-3\u0022\u003E\n               \u003Cp id=\u0022p-12\u0022\u003EUse and timing of invasive strategy\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-4\u0022\u003E\n               \u003Cp id=\u0022p-13\u0022\u003EAnatomical complexities of revascularization, such as diffuse coronary artery disease and microvascular disease\u003C\/p\u003E\n            \u003C\/li\u003E\u003C\/ul\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2010 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\/10\/10\/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_openurl.js?nzmnnq\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?nzmnnq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}