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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\u003EAn analysis of the MR CLEAN trial demonstrated a significant interaction between time from stroke onset to reperfusion and treatment effect, with the decrease in absolute risk difference between treated and untreated patients of almost 7% per hour (\u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.038). The relationship between time to treatment and treatment effect was not statistically significant but is still considered biologically plausible.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eacute ischemic stroke\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eendovascular\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eintra-arterial\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EMR CLEAN\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ETOR\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ETOT\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EPuck Fransen, MD, Erasmus MC University Medical Center, Rotterdam, The Netherlands, reported results of the analyses that examined the interaction between time from stroke onset to treatment (TOT) and time from stroke onset to reperfusion (TOR) and the effect of treatment on clinical outcome in the MR CLEAN trial, demonstrating that TOR significantly affected treatment outcome.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EMR CLEAN was the first study to demonstrate efficacy of intra-arterial treatment received within 6 hours of stroke onset in patients with acute ischemic stroke due to intracranial anterior circulation occlusion [Berkhemer OA et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2015]. According to Dr Fransen, time is an important predictor of clinical outcome in all ischemic diseases, and this analysis was assigned to assess the interaction between TOT and TOR with treatment on clinical outcome and whether treatment was effective in the entire 6-hour time frame used in the trial.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EThe multicenter MR CLEAN was a randomized, prospective, open-label, phase 3 trial with blinded outcome assessment conducted in The Netherlands. The primary outcome measure in this analysis was the score on the modified Rankin Scale (mRS) at 90 days, with adjusted common odds ratio for shift on the mRS as the primary effect parameter.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThe study enrolled a total of 500 patients (167 in early, 168 in medium, and 165 in late TOT groups). The main clinical characteristics\u2014such as patient age, sex, and the National Institute of Health Stroke Scale score at baseline\u2014were similar among the groups.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EThe median TOT (treatment defined as microcatheter in the groin) was 256 minutes, with 11.5% of patients receiving treatment in \u0026lt;\u20093 hours, 45% between 3 and 4.5 hours, 44% between 4.5 and 6 hours, and 8.8% in \u0026gt;\u20096 hours. The median TOR (reperfusion defined as achieving thrombolysis in cerebral infarction grade 2b\/3\u2014which has been regarded as a successful angiographic outcome\u2014or end of the procedure if reperfusion was not reached) was 332 minutes, with 1.5% achieving reperfusion in \u0026lt;\u20093 hours, 22% between 3 and 4.5 hours, 40% between 4.5 and 6 hours, and 37% in \u0026gt;\u20096 hours.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EAn analysis of the relationship between treatment effect and TOT suggested that the absolute risk difference (ARD) in chances of good outcome (mRS, 0-2) between treated and untreated patients was 19% at TOT equal to 2 hours and 3% at TOT equal to 6 hours. This implied a 4% decrease in ARD per hour, which was not statistically significant (\u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.26). However, the decrease in ARD per hour of TOR was calculated to be almost 7% and statistically significant (\u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.038), with ARD of 33% at 2 hours and 6.5% at 6 hours (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). The treatment effect was not statistically significant beyond TOR of 6 hours and 19 minutes.\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\/15\/2\/12.2\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022TOR Affects Chances of Good OutcomeARD, absolute risk difference; lb, lower bound; mRS, modified Rankin Scale; TOR, time from stroke onset to reperfusion; ub, upper bound.Reproduced with permission from P Fransen, MD.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1123318188\u0022 data-figure-caption=\u0022TOR Affects Chances of Good OutcomeARD, absolute risk difference; lb, lower bound; mRS, modified Rankin Scale; TOR, time from stroke onset to reperfusion; ub, upper bound.Reproduced with permission from P Fransen, MD.\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\/15\/2\/12.2\/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\/15\/2\/12.2\/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\/15\/2\/12.2\/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\/15256\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-8\u0022 class=\u0022first-child\u0022\u003ETOR Affects Chances of Good Outcome\u003C\/p\u003E\n               \u003Cp id=\u0022p-9\u0022\u003EARD, absolute risk difference; lb, lower bound; mRS, modified Rankin Scale; TOR, time from stroke onset to reperfusion; ub, upper bound.\u003C\/p\u003E\n               \u003Cp id=\u0022p-10\u0022\u003EReproduced with permission from P Fransen, MD.\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-11\u0022\u003EDr Fransen concluded that there was a significant interaction between TOR and treatment effect, while the interaction between TOT and treatment effect was not statistically significant but is still considered to be biologically possible. The study demonstrated that the probability of a positive outcome decreases rapidly with every hour of reperfusion delay, and patients with acute ischemic stroke should receive appropriate treatment as soon as possible.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 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\/15\/2\/12.2.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?nzlqk4\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?nzlqk4\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}