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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\u003EBoth the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery myocardial revascularization guidelines [Wijns W et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2010] and American College of Cardiology Foundation, American Heart Association, and Society for Cardiovascular Angiography and Interventions percutaneous coronary intervention (PCI) guidelines [Levine GN et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2011] recommend (with a Class I recommendation) the use of a loading dose of a P2Y12 receptor inhibitor before PCI with stenting. This article discusses alternatives to the Class I recommendation.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Einterventional techniques \u0026amp; devices\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiology clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EBoth the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery myocardial revascularization guidelines [Wijns W et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2010] and American College of Cardiology Foundation, American Heart Association, and Society for Cardiovascular Angiography and Interventions percutaneous coronary intervention (PCI) guidelines [Levine GN et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2011] recommend (with a Class I recommendation) the use of a loading dose of a P2Y\u003Csub\u003E12\u003C\/sub\u003E receptor inhibitor before PCI with stenting. David J. Cohen, MD, MSc, University of Missouri at Kansas City, Kansas City, Missouri, USA, suggested that despite the Class I recommendation, data supporting P2Y\u003Csub\u003E12\u003C\/sub\u003E inhibitor preloading before PCI are uncertain, as they are based predominantly on older trials that used conservative management strategies with prolonged treatment delays and with a substantial proportion of benefit occurring before the PCI.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EThe data for the current preloading guidelines come from 3 early trials: Percutaneous Coronary Intervention\u2013Clopidogrel in Unstable Angina to Prevent Recurrent Events [PCI-CURE; Mehta SR et al. \u003Cem\u003ELancet\u003C\/em\u003E 2001], Clopidogrel for the Reduction of Events During Observation [CREDO; Steinhubl SR et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2002], and Clopidogrel as Adjunctive Reperfusion Therapy\u2013Percutaneous Coronary Intervention [CLARITY-PCI; Sabatine MS et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2005], only 2 of which (PCI-CURE and CLARITY-PCI) showed significant reductions in end points with preloading. Of note, 2 of these trials (PCI-CURE and CLARITY-PCI) were subgroup analyses of larger trials based on postrandomization management and therefore were not truly randomized comparisons. CREDO, the only true randomized controlled trial of the 3, failed to show a benefit with preloading. The major concern with all 3 trials is the length of time between preload and PCI (median, 6 days in PCI-CURE; 3\u201324 hours in CREDO; and 2\u20138 days in CLARITY-PCI).\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EUpstream use of P2Y\u003Csub\u003E12\u003C\/sub\u003E loading prior to PCI with ticagrelor was superior to clopidogrel in the Platelet Inhibition and Patient Outcomes trial. However, there has been no study evaluating the potential benefit of pretreatment versus treatment at the time of PCI with ticagrelor.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EA Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST-Elevation Myocardial Infarction [ACCOAST; Montalescot G et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2013] was a Phase 3 trial designed to compare 2 prasugrel loading-dose regimens in patients with non\u2013ST-segment elevation myocardial infarctions (NSTEMIs) with elevated troponin (\u2265 1.5 times the upper limit of normal) who were intended to undergo an early (within 24 hours) invasive management strategy [Montalescot G et al. \u003Cem\u003EAm Heart J\u003C\/em\u003E 2011]. Participants were randomized to either placebo (n = 1996) or prasugrel 30 mg (n = 2037) [Montalescot G et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2013]. Following coronary angiography, subjects in the placebo group intended for PCI received the full loading dose of prasugrel 60 mg, while those in the prasugrel 30 mg group who were intended for PCI received an additional 30 mg of prasugrel. After PCI, all subjects received 5 or 10 mg of prasugrel daily (based on age and weight) for 30 days. The primary end point was a composite of cardiovascular (CV) death, MI, stroke, urgent revascularization, or glycoprotein (GP) IIb\/IIIa bailout, at 7 days. Key safety end points include Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding risks [Montalescot G et al. \u003Cem\u003EAm Heart J\u003C\/em\u003E 2011]. ACCOAST was stopped early because of an increase in major and life-threatening bleeding and no reduction in CV events.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003ESubjects were aged 64 years (mean) and mostly men; about one-quarter were high risk according to the Global Registry of Acute Coronary Events risk score. The median time from first loading dose to coronary angiography was 4.4 hours in the pretreated group and 4.2 hours in the placebo group.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EAt Day 30, preloading was not associated with an incremental benefit on the composite primary end point of CV death, MI, stroke, urgent revascularization, or GP IIb\/IIIa bailout (HR, 0.997; 95% CI, 0.83 to 1.20; p = .98). The absence of additional benefit was consistent for each of the individual end points and among the subgroup of participants who underwent PCI (the majority but not all trial subjects).\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EAlthough relatively infrequent, there was a doubling of TIMI major bleeding among subjects who received the 30-mg prasugrel preload (HR, 2.0; 95% CI, 1.3 to 3.1; p = .002).\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EDr. Cohen concluded that in patients with NSTEMIs undergoing invasive management within 48 hours of admission, pretreatment with prasugrel (compared with treatment started only at the time of PCI) does not decrease major ischemic events but increases major bleeding complications. It is unknown whether these findings apply to patients with longer waiting times or to those treated with other agents (eg, clopidogrel, ticagrelor). Thus, the results showed no benefit of pretreatment, and reexamination of the current guidelines may be warranted.\u003C\/p\u003E\n      \u003C\/div\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\/13\/11.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?nzoyre\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}