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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.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\u003ETreatment with investigative apixaban, an oral factor Xa inhibitor, shows promise as add-on protection against recurrent ischemic cardiovascular events among acute coronary syndrome patients who already are on standard antiplatelet therapy, including aspirin and clopidogrel. But dose-dependent bleeding remains an unresolved problem. This article discusses the Phase 2, Placebo-Controlled, Randomized, Double-Blind, Parallel Arm, Dose-Ranging Study to Evaluate Safety and Efficacy of Apixaban in Patients with a Recent Acute Coronary Syndrome [APPRAISE-1; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00313300\u0026amp;atom=%2Fspmdc%2F8%2F6%2F22.atom\u0022\u003ENCT00313300\u003C\/a\u003E] trial.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiology clinical trials\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         \n         \u003Cp id=\u0022p-2\u0022\u003ETreatment with investigative apixaban, an oral factor Xa inhibitor, shows promise as add-on protection against recurrent ischemic cardiovascular (CV) events among acute coronary syndrome (ACS) patients who already are on standard antiplatelet therapy, including aspirin and clopidogrel. But dose-dependent bleeding remains an unresolved problem.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EInvestigators from the APPRAISE-1 (A Phase 2, Placebo-Controlled, Randomized, Double-Blind, Parallel Arm, Dose-Ranging Study to Evaluate Safety and Efficacy of Apixaban in Patients with a Recent Acute Coronary Syndrome; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00313300\u0026amp;atom=%2Fspmdc%2F8%2F6%2F22.atom\u0022\u003ENCT00313300\u003C\/a\u003E) trial reported their findings in Munich at the European Society of Cardiology Congress 2008.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003E\u201cThe addition of apixaban to standard antiplatelet therapy for 6 months after onset of ACS resulted both in dose-dependent increases in bleeding and in a trend toward a reduction in clinically important ischemic events,\u201d said principal investigator John Alexander, MD, Duke Clinical Research Institute and Duke Heart Center, Durham, NC.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EDr. Alexander noted that one of the most challenging problems in treating ACS patients is finding a drug combination that inhibits clot formation without increasing the risk of serious bleeding. APPRAISE-1 is the first trial of an oral drug that targets factor Xa, a key enzyme in blood coagulation.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EAPPRAISE-1 was a phase 2 study that aimed at defining the optimal dose of apixaban regarding safety and efficacy in patients with a recent onset ACS. The study took place in 2 phases.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EPhase A enrolled 547 patients who manifested ACS within the prior 7 days. Subjects were randomized to placebo (n=184), apixaban 2.5 mg BID (n=179), or apixaban 10 mg QD (n=184). Following the safety review of phase A, the enrollment was continued in phase B, reaching a study total of 1715 subjects. Those who were enrolled after the safety review were randomized to placebo (n=427), apixaban 2.5 mg BID (n=138), apixaban 10 mg QD (n=134), apixaban 10 mg BID (n=248), and apixaban 20 mg QD (n=221).\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EThe primary safety outcome was major bleeding, as measured with the International Society of Thrombosis and Hemostasis (ISTH) scale, or clinically relevant non-major (CRNM) bleeding. The secondary efficacy outcome was a composite of CV death, myocardial infarction (MI), severe recurrent ischemia, and ischemic stroke.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EDuring phase B of the trial, the higher apixaban dosing groups (10 mg BID and 20 mg QD) were discontinued due to unacceptably increased rates of total bleeding.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EThe index event was ST-elevation MI in 67% of patients. Investigators reported that the incidence of major or CRNM bleeding was 5.7% for apixaban 2.5 mg BID (n=315), 7.9% for apixaban 10 mg QD (n=315), and 3.0% for placebo (n=599). Bleeding at both apixaban dosages was higher compared with placebo (2.5 mg BID: HR 1.78; 95% CI, 0.91 to 3.48; p=0.09; and 10 mg QD: HR 2.45; 95% CI, 1.31 to 4.61; p=0.005; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). The absolute rates of bleeding were higher in patients on clopidogrel (7.0% for apixaban 2.5 mg BID, 9.1% for apixaban 10 mg QD, and 3.1% for placebo) compared with aspirin (2.4% for apixaban 2.5 mg BID, 4.1% for apixaban 10 mg QD, and 2.7% for placebo).\u003C\/p\u003E\n         \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\/8\/6\/22\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022ISTH Major or CRNM Bleeding.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1591493206\u0022 data-figure-caption=\u0022ISTH Major or CRNM Bleeding.\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\/8\/6\/22\/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\/8\/6\/22\/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\/8\/6\/22\/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\/11106\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\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-11\u0022 class=\u0022first-child\u0022\u003EISTH Major or CRNM Bleeding.\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-12\u0022\u003EFor the combined secondary efficacy endpoint outcome of CV death, MI, severe recurrent ischemia, or ischemic stroke, investigators reported incidence rates of 7.6% for apixaban 2.5 mg BID (n=317), 8.7% for apixaban 10 mg QD (n=318), and 6.0% for placebo (n=611). These findings suggested a trend toward efficacy versus placebo (2.5 mg BID: HR 0.73; 95% CI, 0.44 to 1.19; p=0.21; and 10 mg QD: HR 0.61; 95% CI, 0.35 to 1.04; p=0.07), but the difference did not reach statistical significance (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E).\u003C\/p\u003E\n         \u003Cdiv id=\u0022F2\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\/8\/6\/22\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Ischemic Outcome.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1591493206\u0022 data-figure-caption=\u0022Ischemic Outcome.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/6\/22\/F2.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\/8\/6\/22\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\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\/8\/6\/22\/F2.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\/11110\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\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-13\u0022 class=\u0022first-child\u0022\u003EIschemic Outcome.\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-14\u0022\u003EDr. Alexander said that while the clinical findings in APPRAISE-1 were inconclusive regarding efficacy, apixaban at 5 mg and 10 mg daily appears to be promising for ACS patients and warrants further clinical investigation in large, well-controlled trials.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2008 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\/8\/6\/22.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?nzmd0d\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?nzmd0d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}