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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\u003EEffective adjunctive treatment of acute coronary syndrome with antithrombin therapy is essential to reduce ischemic complications, and researchers continue to compare novel antithrombotic agents with currently available ones in an effort to optimize outcomes. These comparisons require careful evaluation of the benefit-risk balance, with a primary consideration of reduction of ischemic complications weighed against bleeding risk.\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\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EEffective adjunctive treatment of acute coronary syndrome (ACS) with antithrombin therapy is essential to reduce ischemic complications, and researchers continue to compare novel antithrombotic agents with currently available ones in an effort to optimize outcomes. These comparisons require careful evaluation of the benefit\u2013risk balance, with a primary consideration of reduction of ischemic complications weighed against bleeding risk.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EUnfractionated heparin (UFH) was once the standard of care for patients with ACS based on studies that showed that the combination of aspirin and heparin was associated with a substantially lower risk of myocardial infarction (MI) and death than either agent alone or placebo for patients with unstable angina or non\u2013ST\u2013elevation MI (NSTEMI) [Wallentin L et al. \u003Cem\u003ELancet\u003C\/em\u003E 1990; Oler A et al. \u003Cem\u003EJAMA\u003C\/em\u003E 1996].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EHowever, a primary problem with UFH is the variability in its therapeutic effect, said Marc Cohen, MD, FACC, Newark Beth Israel Medical Center, New Jersey, USA. In one study, the initial activated partial thromboplastin times (aPTTs; measured 4 to 8 hours after the start of therapy) were therapeutic in one\u2013third of patients, were low in approximately 20%, were high in approximately 17%, and were markedly low and markedly high in 13% and 16%, respectively [Cheng S et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2009]. When the results were further analyzed, \u201cimportant lessons emerged,\u201d said Dr. Cohen. Patients who had markedly high aPTTs in response to heparin were more likely to be older, or female, have low body weight, and have renal insufficiency. These variables should be familiar because they are the same as those that are associated with an increased risk for bleeding.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EWhen low\u2013molecular\u2013weight heparin was evaluated as an alternative to UFH, several advantages were identified. \u201cClinical data are available with enoxaparin in all types of ACS, with better outcomes than for UFH,\u201d said Gilles Montalescot, MD, Piti\u00e9-Salp\u00eatri\u00e8re University Hospital, Paris, France. In a meta\u2013analysis of six studies that involved patients with NSTEMI or STEMI, enoxaparin led to significantly lower rates of death or reinfarction (p=0.043) with no excess of major bleeding (p=0.42) [Murphy S et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2007].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EFor patients who were treated with fibrinolysis for STEMI, enoxaparin significantly reduced death or reinfarction at 30 days compared with UFH (9.9% vs 12.0%; RR, 0.83; 95% CI, 0.77 to 0.90; p\u0026lt;0.0001), whether patients underwent subsequent percutaneous coronary intervention (PCI) or not [Antman EM et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2006]. There was a significantly higher rate of TIMI major bleeding (2.1% vs 1.4%; p\u0026lt;0.001) but not intracranial hemorrhage. The drug became the standard of care for patients who were receiving fibrinolysis.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EEnoxaparin and UFH were compared head\u2013to\u2013head among patients who were scheduled to have primary PCI in the ATOLL study [Montalescot G et al. \u003Cem\u003ELancet\u003C\/em\u003E 2011]. The results demonstrated that enoxaparin (intravenous 0.5 mg\/kg bolus) was associated with a 17% reduction of the primary endpoint of death, complication of MI, procedure failure, or major bleeding (28% vs 33.7%; p=0.06). The main secondary endpoint (death, recurrent ACS, or urgent revascularization) was significantly lower among patients who were treated with enoxaparin compared with UFH (6.7% vs 11.3%; p=0.01). The study represented the first time that two\u2013thirds of patients had primary PCI with radial access, which reduced major bleeding, blunting the reduction of the combined efficacy and safety primary endpoint with enoxaparin. In a subsequent meta\u2013analysis, enoxaparin was superior to UFH in reducing mortality and bleeding outcomes during PCI, particularly among patients with STEMI (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Silvain J et al. \u003Cem\u003EBMJ\u003C\/em\u003E 2012].\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\/12\/4\/28\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Mortality in Meta Analysis.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-324124194\u0022 data-figure-caption=\u0022Mortality in Meta Analysis.\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\/12\/4\/28\/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\/12\/4\/28\/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\/12\/4\/28\/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\/14007\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 attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EMortality in Meta Analysis.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced from the \u003Cem\u003EBritish Medical Journal\u003C\/em\u003E, Silvain J et al, 344:e553, 2012 with permission from BMJ Publishing Group Ltd.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-9\u0022\u003EThe 2011 American College of Cardiology Foundation\/American Heart Association (ACCF\/AHA) guidelines for PCI indicate that enoxaparin and UFH should not be given together; the combination is harmful due to an excess of major bleeding [Levine GN et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EProf. Montalescot concluded, \u201cGiven its wide availability and low cost, enoxaparin is an attractive strategy to improve outcomes in the large number of patients undergoing PCI worldwide.\u201d\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EAnother anticoagulant, fondaparinux, may be used instead of enoxaparin. In the context of an early invasive or conservative strategy, fondaparinux is a Class I, level A recommendation in the European Cardiology Society guidelines for the management of NSTE\u2013ACS [Hamm CW et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2011]. In the 2011 focused update to the ACC\/AHA guidelines for NSTE\u2013ACS, fondaparinux is a Class I, level B recommendation in the setting of a conservative strategy [Wright RS et al. \u003Cem\u003EJACC\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EBivalirudin represents a third and perhaps safer option for anticoagulation in ACS. This small\u2013molecule agent has theoretical advantages over heparin in that it inhibits both fluid\u2013phase and clot\u2013bound thrombin and also inhibits rather than activates platelets as heparin does, explained Gregg W. Stone, MD, Columbia University Medical Center, Cardiovascular Research Foundation, New York, New York, USA.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EBivalirudin has been evaluated for use in both NSTE\u2013ACS and STEMI, and studies have consistently shown lower rates of bleeding, with similar ischemic complications, yielding a favorable net clinical benefit outcome. The ACUITY study randomized 13,819 patients with moderate\u2013high risk ACS who were undergoing an early invasive strategy to one of three groups: UFH or enoxaparin plus a glycoprotein IIb\/IIIa (GP) inhibitor (the standard of care at the time of the study), bivalirudin plus a GP inhibitor, or bivalirudin alone [Stone GW et al. \u003Cem\u003EN Eng J Med\u003C\/em\u003E 2006]. There was no difference in the composite ischemia endpoint (death, MI, or a recurrent ischemia that necessitated repeat revascularization) at 30 days between the three groups (7.4% [heparin plus a GP inhibitor] vs 7.9% [bivalirudin plus a GP inhibitor] vs 8.0% [bivalirudin alone]), but bivalirudin alone was associated with the lowest rate of bleeding (5.7% [heparin plus a GP inhibitor] vs 5.3% [bivalirudin plus a GP inhibitor] vs 3.1% [bivalirudin alone]). Adding a GP inhibitor to bivalirudin was not beneficial, in terms of reducing either ischemia or bleeding.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003ESimilar results have been reported in other studies of patients with NSTE\u2013ACS and STEMI comparing bivalirudin alone with the combination of heparin plus a GP inhibitor [Stone GW et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008; Kastrati A et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011]. In higher risk patients with STEMI, a lower rate of bleeding events was found with bivalirudin but at the expense of more acute stent thrombosis (1.3% bivalirudin vs 0.3% heparin plus GP inhibitor; p\u0026lt;0.001) [Stone GW et al. \u003Cem\u003EN Eng J Med\u003C\/em\u003E. 2008]. Long\u2013term follow\u2013up for this cohort showed a lower rate of all\u2013cause mortality at 3 years with bivalirudin [Stone GW et al. \u003Cem\u003ELancet\u003C\/em\u003E 2011]. The mechanism for this mortality reduction is not well understood.\u003C\/p\u003E\u003Cp id=\u0022p-15\u0022\u003EIn\u2013hospital mortality was also reduced with bivalirudin compared with heparin plus a GP inhibitor (3.2% vs 4.0%; p=0.011) in an analysis of the data for nearly 60,000 patients who had STEMI and primary angioplasty in the PREMIERE perspective database [Pinto DS et al. \u003Cem\u003ECirc Cardiovasc Qual Outcomes\u003C\/em\u003E 2012]. Bivalirudin also reduced bleeding (6.9% vs 10.5%; p\u0026lt;0.0001) and transfusion (5.9% vs 7.6%; p\u0026lt;0.0001), and these reductions led to decreased length of stay and lower costs.\u003C\/p\u003E\u003Cp id=\u0022p-16\u0022\u003EAs a result of these studies, bivalirudin is one of the Class I antithrombotic therapies that are recommended by numerous practice guidelines for treatment of patients with either NSTEMI or STEMI who are to have an early invasive strategy.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 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\/12\/4\/28.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?nznhr1\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?nznhr1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}