Extending thrombolysis to 4.5-9 h and wake-up stroke using perfusion imaging : a systematic review and meta-analysis of individual patient data

Show full item record



Permalink

http://hdl.handle.net/10138/312914

Citation

EXTEND Investigator , ECASS-4 Investigator , EPITHET Investigator , Campbell , B C , Ma , H , Curtze , S , Donnan , G A & Kaste , M 2019 , ' Extending thrombolysis to 4.5-9 h and wake-up stroke using perfusion imaging : a systematic review and meta-analysis of individual patient data ' , Lancet , vol. 394 , no. 10193 , pp. 139-147 . https://doi.org/10.1016/S0140-6736(19)31053-0

Title: Extending thrombolysis to 4.5-9 h and wake-up stroke using perfusion imaging : a systematic review and meta-analysis of individual patient data
Author: EXTEND Investigator; ECASS-4 Investigator; EPITHET Investigator; Campbell, Bruce C.; Ma, Henry; Curtze, Sami; Donnan, Geoffrey A.; Kaste, Markku
Other contributor: University of Helsinki, Department of Neurosciences
University of Helsinki, Clinicum



Date: 2019-07-13
Language: eng
Number of pages: 9
Belongs to series: Lancet
ISSN: 0140-6736
DOI: https://doi.org/10.1016/S0140-6736(19)31053-0
URI: http://hdl.handle.net/10138/312914
Abstract: Background Stroke thrombolysis with alteplase is currently recommended 0-4.5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4.5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis. Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials. gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged =18 years) with ischaemic stroke treated more than 4.5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. Findings We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1.86, 95% CI 1.15-2.99, p=0.011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9.7, 95% CI 1.23-76.55, p=0.031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1.55, 0.81-2.96, p=0.66). Interpretation Patients with ischaemic stroke 4.5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis. Copyright (c) 2019 Elsevier Ltd. All rights reserved.
Subject: ACUTE ISCHEMIC-STROKE
REPERFUSION
DIFFUSION
ALTEPLASE
MULTICENTER
MISMATCH
ONSET
TIME
3112 Neurosciences
3124 Neurology and psychiatry
3121 General medicine, internal medicine and other clinical medicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
Extending_throm ... ndividual_patient_data.pdf 447.1Kb PDF View/Open
1_s2.0_S0140673619310530_main.pdf 447.0Kb PDF View/Open

This item appears in the following Collection(s)

Show full item record