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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\u003EResults from the phase 2 Study Program to Evaluate the Prevention of Ischemia with Direct Xa inhibition [SEPIA-ACS1 TIMI 42; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00317395\u0026amp;atom=%2Fspmdc%2F9%2F4%2F20.1.atom\u0022\u003ENCT00317395\u003C\/a\u003E] study provided promising data that otamixaban, an intravenous direct Factor Xa inhibitor, at intermediate doses may be associated with a lower risk of ischemic events with similar bleeding compared with the current standard of care in patients with non-ST elevation acute coronary syndromes (NSTE-ACS) [Sabatine MS et al. \u003Cem\u003ELancet\u003C\/em\u003E 2009].\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\u003EMyocardial Infarction Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EResults from the phase 2 SEPIA-ACS1 TIMI 42 (Study Program to Evaluate the Prevention of Ischemia with Direct Xa inhibition; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00317395\u0026amp;atom=%2Fspmdc%2F9%2F4%2F20.1.atom\u0022\u003ENCT00317395\u003C\/a\u003E) study, presented by Marc S. Sabatine, MD, MPH, Brigham and Women\u0027s Hospital, Boston, MA, provide promising data that otamixaban, an intravenous direct Factor Xa inhibitor, at intermediate doses may be associated with a lower risk of ischemic events with similar bleeding compared with the current standard of care in patients with non-ST elevation acute coronary syndromes (NSTE-ACS) [Sabatine MS et al. \u003Cem\u003ELancet\u003C\/em\u003E 2009].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThis phase 2, randomized, double-blind, dose-ranging study enrolled patients with moderate- to high-risk NSTE-ACS in whom an early invasive strategy was planned. The primary efficacy endpoint was the composite of all-cause death, new myocardial infarction (MI), severe recurrent ischemia that required urgent revascularization, or bailout use of a glycoprotein IIb\/IIIa inhibitor (GPI) through Day 7. The primary safety endpoint was TIMI major or minor bleeding that was unrelated to coronary artery bypass graft (CABG).\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThree thousand two hundred forty-one patients were randomized within 24 hours of presentation with NSTE-ACS to receive a bolus infusion of otamixaban 0.08 mg\/kg that was followed by infusions of 0.035, 0.070, 0.105, 0.140, or 0.175 mg\/kg\/hr, or to unfractionated heparin (UFH; 60-IU\/kg bolus followed by an infusion of 12 IU\/kg\/hr) plus eptifibatide (180-\u03bcg\/kg bolus followed by an infusion of 1.0\u20132.0 \u03bcg\/kg\/min). Subjects were aged a mean of 61 years; 31% was female. ST segment deviation \u22650.1 mV was present in 57%; 77% had an elevated cardiac biomarker of necrosis. Of those who were enrolled, 99% underwent angiography, 63% underwent PCI, and 4% underwent CABG. Most patients were treated with aspirin (98%) and clopidogrel (98%).\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThere was no significant difference in the rate of the primary efficacy endpoint across otamixaban arms; however, in all but the 0.035-mg\/kg\/hr arm (stopped early due to inadequate anticoagulation), the point estimate of death, second heart attack, or additional coronary complications were lower with otamixaban than with UFH+eptifibitide. Treatment with intermediate doses of otamixaban (0.105 or 0.140 mg\/kg\/hr) resulted in an approximate 40% reduction in the primary efficacy endpoint (RR, 0.61; 95% CI, 0.36 to 1.02 and RR, 0.58; 95% CI, 0.34 to 0.996, respectively). The benefits were driven primarily by a reduction in death or MI (RR, 0.52; 95% CI, 0.28 to 0.98 and RR, 0.56; 95% CI, 0.30 to 1.03, for the 0.105- and 0.140-mg\/kg\/hr doses, respectively).\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EUrgent revascularization and the need for GPI bailout occurred in \u0026lt;1% of patients. The rates of thrombotic complications in patients who underwent PCI (n=2032) were similar between the intermediate doses of otamixaban (range 2.9% to 3.5%) and the control arm (2.4%).\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThere was a significant dose-dependent increase in the primary safety endpoint of TIMI major or minor bleeding with otamixaban (p=0.001 for trend); however, the rates in the intermediate-dose arms (3.1% for 0.105 mg\/kg\/hr and 3.4% for 0.140 mg\/kg\/hr) were similar to that observed with UFH+eptifibitide (2.7%). The relative risk of major bleeding was higher in the highest-dose group compared with control (RR, 1.26; 95% CI, 1.06 to 3.85) but was similar in the intermediate-dose groups (RR, 1.15; 95% CI, 0.57 to 2.32 for 0.105 mg\/kg\/hr and RR, 1.26; 95% CI, 0.63 to 2.52 for 0.140 mg\/kg\/hr).\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003E\u201cThe data show that intermediate doses of otamixaban may offer a substantial reduction in major coronary complications in patients presenting with an acute coronary syndrome, with bleeding rates comparable to current therapy,\u201d said Dr. Sabatine. \u201cThese findings will need to be tested in a large phase 3 trial to establish the definitive role of otamixaban in the treatment of acute coronary syndromes.\u201d\u003C\/p\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\/20.1.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?nzmj11\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}