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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\u003EIntravenous recombinant tissue plasminogen activator (rt-PA) is effective in the treatment of acute ischemic stroke; however, there has been some doubt regarding the timing of its use, its use in older patients, as well as its use in patients with different levels of stroke severity. This article presents data indicating that regardless of patient age, rt-PA improves the odds of surviving with no significant disability when delivered within 4.5 hours of stroke onset, with earlier treatment leading to proportionally bigger benefit.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECerebrovascular Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EIschemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECerebrovascular Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EIschemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EIntravenous recombinant tissue plasminogen activator (rt-PA) is effective in the treatment of acute ischemic stroke; however, there has been some doubt regarding the timing of its use, its use in older patients, as well as its use in patients with different levels of stroke severity. Jonathan R. Emberson, MSc, PhD, University of Oxford, United Kingdom, presented data indicating that regardless of patient age, rt-PA improves the odds of surviving with no significant disability when delivered within 4.5 hours of stroke onset, with earlier treatment leading to proportionally bigger benefit.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe goal of this independent meta-analysis was to examine the extent to which treatment delay, age, and stroke severity modify the effect of rt-PA on stroke outcomes. The effects of rt-PA on the risk of symptomatic intracranial hemorrhage (sICH) and mortality was also assessed. The primary efficacy outcome was the odds of achieving an mRS score of 0\/1 at 3 to 6 months post stroke. Safety endpoints included 90-day mortality, sICH defined by parenchymal hemorrhage of type 2 (PH2) within 7 days, or Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) definition of PH2 type hemorrhage within 36 hours, and fatal ICH within 7 days. The full analysis plan has been previously published [Stroke Thrombolysis Trialists\u0027 Collaborative Group. \u003Cem\u003EInt J Stroke\u003C\/em\u003E 2013].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe analysis included data from 6756 participants from nine trials (Alteplase Thrombolysis for Acute Non-interventional Therapy in Ischemic Stroke trials A\/B; European Cooperative Acute Stroke Studies I\/II\/III; Echoplanar Imaging Thrombolytic Evaluation Trial; National Institute of Neurological Disorders and Stroke trials A\/B; and the Third International Stroke Trial [IST-3]) in which subjects were randomized to rt-PA (n=3391) or control (n=3365). Approximately 44% of the subjects were from IST-3. Although these patients were older than those in the other trials (77 vs 66 years), mean treatment delay was similar (4.2 vs 3.9 hours), and average stroke severity was the same NIHSS score of 12).\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe odds of achieving an mRS 0\/1 were significantly improved with rt-PA, with the benefits being more significant with earlier treatment. There was a significant 75% improvement in the odds of a patient achieving mRS 0\/1 when treatment was delivered within 3 hours (95% CI, 1.35 to 2.27) and a significant 26% improvement when delivered between 3 and 4.5 hours post event (95% CI, 1.05 to 1.51). There was a 15% nonsignificant improvement when treatment was delivered \u0026gt;4.5 hours post stroke. There was no evidence that age or stroke severity altered the proportional benefits of rt-PA and clear evidence of benefit in a subgroup of patients aged \u0026gt;80 years (OR, 1.56; 95% CI, 1.17 to 2.08).\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe average incidence of ICH was low in the control group but increased among patients receiving rt-PA. This was particularly true for fatal ICH within 7 days in the rt-PA group. By 90 days, the rate of excess death from any cause was not significantly different (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). The 11% relative difference in excess death at 90 days was primarily driven by the increased risk of fatal ICH by Day 7 in the rt-PA group.\u003C\/p\u003E\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\/14260\/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\/14260\/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\/14260\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\u003ESafety Outcomes\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-9\u0022\u003EAlthough the proportional increase in the early risk of fatal ICH was similar irrespective of treatment delay, age, or stroke severity, and was present even among those patients who were treated within 3 hours, the absolute risk increased with stroke severity. Dr. Emberson suggested that since the rates of death from all causes between Days 8 and 90 did not differ significantly, and since there was no excess in 90-day mortality among those treated earlier, that early treatment with rt-PA may contribute to a late benefit in mortality among patients who survive the first week following their stroke.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 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\/14\/1\/11.1.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?nzpd43\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?nzpd43\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}