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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\u003EThe Clopidogrel optimal loading dose Usage to Reduce Recurrent Events-Organization to Assess Strategies in Ischemic Syndromes [CURRENT-OASIS 7] trial was a 2\u00d72 factorial, open-label, randomized trial to determine optimal clopidogrel and aspirin dosing in subjects with acute coronary syndrome within 24 hours of ischemic symptoms. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke to Day 30.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EMyocardial Infarction\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EThrombotic Disorders Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInterventional Techniques \u0026amp; Devices\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThe Clopidogrel optimal loading dose Usage to Reduce Recurrent EveNTs-Organization to Assess Strategies in Ischemic Syndromes (CURRENT-OASIS 7) trial was a 2\u00d72 factorial, open-label, randomized trial to determine optimal clopidogrel and aspirin dosing in subjects with acute coronary syndrome (ACS) within 24 hours of ischemic symptoms. Subjects were randomly assigned to either double-dose clopidogrel for 7 days (600-mg loading dose, followed by 150 mg daily on Days 2 to 7, then 75 mg daily to Day 30) or the standard-dose regimen (300-mg loading dose, followed by 75 mg daily). The second randomization was to open-label, high-dose (300\u2013325 mg) or low-dose (75\u2013100 mg) aspirin daily for 30 days. The primary outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke to Day 30. The primary safety outcome was major bleeding. The results were presented by Professor Shamir Mehta, MD, McMaster Clinic, Hamilton, Ontario, Canada.\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EPrimary Analysis\u003C\/h2\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EA total of 25,087 subjects were enrolled, including 71% with UA\/NSTEMI and 29% with STEMI. PCI was performed at the discretion of the treating physician in 70% of the trial cohort. The primary analysis for this 2\u00d72 factorial trial showed a significant interaction for the primary endpoint between high-dose and low-dose aspirin and double-dose and standard-dose clopidogrel groups (p=0.043). Subjects who were randomized to high-dose aspirin had lower rates of the primary endpoint on double-dose clopidogrel compared with standard-dose clopidogrel (3.8% vs 4.6%; RR, 0.83; 95% CI, 0.70 to 0.99; p=0.036). This difference was not seen with double-dose versus standard-dose clopidogrel in the low-dose aspirin strata (4.5% vs 4.2%; RR, 1.07; 95% CI, 0.91 to 1.27; p=0.42). For the aspirin dose comparison, there was no difference in rates of the primary endpoint between high-dose and low-dose aspirin (4.2% vs 4.4%; HR, 0.96; 95% CI, 0.85 to 1.08; p=0.47). On pooling subjects across aspirin strata, there was no difference in the primary endpoint between double-dose and standard-dose clopidogrel (4.2% vs 4.4%; HR, 0.95; 95% CI, 0.84 to 1.07; p=0.37).\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EPCI Subgroup Analyses\u003C\/h2\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EIn a postrandomization (improper subgroup) analysis of the pooled cohort that examined patients who were undergoing PCI only (17,232 subjects), there were lower rates of the primary endpoint with double-dose compared with standard-dose clopidogrel (3.9% vs 4.5%). In patients who were not undergoing PCI, the rate of the primary endpoint did not favor double-dose clopidogrel (4.9% vs 4.2%). The main reduction in events with double-dose clopidogrel among subjects who were undergoing PCI was for MI (2.0% vs 2.6%), with no difference in the rate of CV death. Definite or probable stent thrombosis was also lower with double-dose clopidogrel (1.6% vs 2.3%).\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ESafety Analysis\u003C\/h2\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThe primary safety endpoint of CURRENT major bleeding was increased with double-dose clopidogrel (2.5% vs 2.0%; HR, 1.25; 95% CI, 1.05 to 1.47; p=0.01), with an associated increased need for transfusion (2.2% vs 1.8%; HR, 1.26; 95% CI, 1.06 to 1.51; p=0.01). There were no differences in TIMI major bleeding, fatal bleeding, intracranial hemorrhage, or coronary artery bypass graft related major bleeding between the clopidogrel doses. With high-dose compared with low-dose aspirin, there was no difference in CURRENT major bleeding; overall (2.3% vs 2.3%; p=0.90), but a trend toward more gastrointestinal bleeding (0.38% vs 0.24%; p=0.051).\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section discussion\u0022 id=\u0022sec-4\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EInterpretation\u003C\/h2\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EOverall, the results of this trial are complex, due to the factorial design and presence of a statistically significant interaction between aspirin and clopidogrel dose for the primary endpoint. Double-dose clopidogrel reduced the primary endpoint in the high-dose aspirin strata by 17% but was associated with more bleeding and transfusion overall. The data that are available thus far in the postrandomization subgroup of subjects who are undergoing PCI must be interpreted with caution, given the potential for bias in such unadjusted analyses of improper subgroups. Further investigation will be important in understanding the possible reasons why double-dose clopidogrel may provide differential benefit in patients who are undergoing PCI, dependent upon the dose of aspirin administered. Additional adjusted analyses of the postrandomization PCI subgroup that account for events post-PCI are also needed. Careful consideration will be important when integrating these results into clinical practice, which likely will have bearing on future practice guidelines.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2009 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\/9\/4\/15.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?nzmisp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}