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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\u003EA single-stranded 2\u2032-O-(2-methoxyethyl) antisense oligonucleotide to factor XI, is a promising new investigational antithrombotic agent that reduces the incidence of venous thrombosis in patients undergoing total knee replacement without increasing the incidence of bleeding episodes. The lower dose of FXI-ASO is noninferior to enoxaparin and the higher dose significantly reduces the risk of venous thromboembolism compared with enoxaparin.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eelective total knee arthroplasty\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Easymptomatic deep vein thromboembolism\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Econfirmed symptomatic venous thromboembolism\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eenoxaparin\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group drug\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EFXI-ASO\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EActive Comparator-Controlled Study to Assess Safety and Efficacy of ISIS-FXIRx in Total Knee Arthroplasty\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EWithout prophylaxis, patients undergoing total knee arthroplasty (TKA) are at high risk for postoperative venous thromboembolism (VTE). Although traditional anticoagulants (eg, factor Xa or thrombin inhibitors) are effective, they are associated with a risk of bleeding. Patients with a severe factor XI (FXI) deficiency appear to have protection against deep vein thrombosis (DVT) [Salomon O et al. \u003Cem\u003EThromb Haemost\u003C\/em\u003E. 2011], and preclinical studies suggest that targeting FXI might reduce thrombosis without affecting hemostasis [Crosby JR et al. \u003Cem\u003EArterioscler Thromb Vasc Biol.\u003C\/em\u003E 2013; Zhang H et al. \u003Cem\u003EBlood\u003C\/em\u003E. 2010]. Thus, FXI-directed agents are being investigated in clinical studies. One such agent is a second-generation single-stranded 2\u2032-O-(2-methoxyethyl) antisense oligonucleotide to FXI (FXI-ASO).\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EHarry R. B\u00fcller, MD, Academic Medical Center, Amsterdam, Netherlands, presented the results of the Active Comparator-Controlled Study to Assess Safety and Efficacy of ISIS-FXIRx in Total Knee Arthroplasty [B\u00fcller HR et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2014]. This phase 2 open-label trial assessed the safety and efficacy of multiple subcutaneous doses of FXI-ASO in patients undergoing elective TKA.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EPatients were randomly assigned 1:3 to enoxaparin, 40 mg, pre- or post-TKA for at least 8 consecutive days (n\u2009=\u200972) or to FXI-ASO, 200 mg (n\u2009=\u2009144) or 300 mg (n\u2009=\u200977), on days 1, 3, 5, 8, 15, 22, and 29; 6 hours after TKA surgery (on day 36); and on day 39. Patients underwent bilateral venography on day 10\u2009\u00b1\u20092 post-TKA. Patients were followed to day 136.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThe primary efficacy outcome was the composite of asymptomatic deep VTE detected by venography and confirmed symptomatic VTE. The secondary efficacy outcome included components of the primary efficacy outcome and the extent of VTE on venography. The primary safety outcome was a composite of major and clinically relevant nonmajor bleeding.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EThe demographics, clinical characteristics, and compliance with treatment were typical for patients undergoing TKA. About 80% were women with a mean age of 64 years. Treatment groups were well balanced for other factors, including mean FXI activity. Efficacy outcomes are shown in \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E.\u003C\/p\u003E\n         \u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/11626\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/11626\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11626\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\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EEfficacy Outcomes\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-13\u0022\u003EBoth doses of FXI-ASO lowered FXI activity to a greater extent than enoxaparin, and more patients receiving the 300-mg dose of FXI-ASO had FXI levels\u2009\u2264\u20090.2 U\/mL (59.2%) than did patients receiving the 200-mg dose (14.9%). The rates of VTE were lower in patients with FXI\u2009\u2264\u20090.2 U\/mL that for those with FXI\u2009\u0026gt;\u20090.2 U\/mL; the risk difference for FXI-ASO vs enoxaparin for patients with FXI\u2009\u2264\u20090.2 U\/mL was \u221225.6% (\u003Cem\u003EP\u003C\/em\u003E\u2009\u0026lt;\u2009.001); for those with FXI\u2009\u0026gt;\u20090.2 U\/mL, there was no significant difference (\u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.42).\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003EThe safety outcomes are shown in \u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E.\u003C\/p\u003E\n         \u003Cdiv id=\u0022T2\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/11628\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/11628\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11628\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\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-15\u0022 class=\u0022first-child\u0022\u003ESafety Outcomes, No.\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-17\u0022\u003EThis study shows that FXI activity might play a role in the development of postoperative VTE and supports the concept that thrombosis and hemostasis can be dissociated. Reducing FXI levels using an ASO is an effective method for prevention of VTE and appears to be safe and well tolerated.\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 SAGE Publications\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\/55\/10.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?nzo9aq\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_tables.js?nzo9aq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}