Extending thrombolysis to 4·5–9 h and wake-up stroke using perfusion imaging

a systematic review and meta-analysis of individual patient data

EXTEND, ECASS-4, and EPITHET Investigators

研究成果: 雜誌貢獻文章

7 引文 (Scopus)

摘要

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. Funding: None.
原文英語
頁(從 - 到)139-147
頁數9
期刊The Lancet
394
發行號10193
DOIs
出版狀態已發佈 - 七月 13 2019

指紋

Perfusion Imaging
Meta-Analysis
Stroke
Tissue Plasminogen Activator
Placebos
Cerebral Hemorrhage
Odds Ratio
Perfusion
Logistic Models
Diffusion Magnetic Resonance Imaging
National Institutes of Health (U.S.)
Brain
PubMed

ASJC Scopus subject areas

  • Medicine(all)

引用此文

Extending thrombolysis to 4·5–9 h and wake-up stroke using perfusion imaging : a systematic review and meta-analysis of individual patient data. / EXTEND, ECASS-4, and EPITHET Investigators.

於: The Lancet, 卷 394, 編號 10193, 13.07.2019, p. 139-147.

研究成果: 雜誌貢獻文章

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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",
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. Funding: None.",
author = "{EXTEND, ECASS-4, and EPITHET Investigators} and Hsu, {C. T.} and J. Liu and Chen, {T. C.} and Chen, {Y. Y.} and Lin, {C. M.} and Ho, {S. C.} and Hsiao, {P. M.} and Tsai, {C. K.} and Huang, {W. S.} and Yang, {Y. W.} and Huang, {H. Y.} and Wang, {W. C.} and Liu, {C. H.} and Lu, {M. K.} and Lu, {C. H.} and Wu, {Y. H.} and Huang, {S. C.} and Tseng, {C. H.} and Tseng, {L. T.} and Hsu, {C. T.} and Tsai, {H. T.} and Chen, {H. F.} and Lu, {C. J.} and Lin, {C. H.} and Huang, {C. C.} and Chu, {H. J.} and Lee, {C. Y.} and Chang, {W. H.} and Lo, {Y. C.} and Hsu, {Y. D.} and Chen, {C. H.} and Tang, {S. C.} and Tsai, {L. K.} and Yeh, {S. J.} and Lee, {Y. C.} and Wang, {Y. T.} and Chung, {T. C.} and Hu, {C. J.} and L. Chan and Lien, {L. M.} and Yeh, {H. L.} and Yeh, {J. H.} and Chen, {W. H.} and A. Chang and Lee, {I. Y.} and Huang, {M. Y.} and Lee, {J. T.} and Hsu, {Y. D.} and Lin, {C. C.} and Cheng, {C. A.} and Yen, {C. H.} and Tsai, {C. K.} and A. Lee and Chen, {C. I.} and Hsu, {C. T.}",
year = "2019",
month = "7",
day = "13",
doi = "10.1016/S0140-6736(19)31053-0",
language = "English",
volume = "394",
pages = "139--147",
journal = "The Lancet",
issn = "0140-6736",
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TY - JOUR

T1 - Extending thrombolysis to 4·5–9 h and wake-up stroke using perfusion imaging

T2 - a systematic review and meta-analysis of individual patient data

AU - EXTEND, ECASS-4, and EPITHET Investigators

AU - Hsu, C. T.

AU - Liu, J.

AU - Chen, T. C.

AU - Chen, Y. Y.

AU - Lin, C. M.

AU - Ho, S. C.

AU - Hsiao, P. M.

AU - Tsai, C. K.

AU - Huang, W. S.

AU - Yang, Y. W.

AU - Huang, H. Y.

AU - Wang, W. C.

AU - Liu, C. H.

AU - Lu, M. K.

AU - Lu, C. H.

AU - Wu, Y. H.

AU - Huang, S. C.

AU - Tseng, C. H.

AU - Tseng, L. T.

AU - Hsu, C. T.

AU - Tsai, H. T.

AU - Chen, H. F.

AU - Lu, C. J.

AU - Lin, C. H.

AU - Huang, C. C.

AU - Chu, H. J.

AU - Lee, C. Y.

AU - Chang, W. H.

AU - Lo, Y. C.

AU - Hsu, Y. D.

AU - Chen, C. H.

AU - Tang, S. C.

AU - Tsai, L. K.

AU - Yeh, S. J.

AU - Lee, Y. C.

AU - Wang, Y. T.

AU - Chung, T. C.

AU - Hu, C. J.

AU - Chan, L.

AU - Lien, L. M.

AU - Yeh, H. L.

AU - Yeh, J. H.

AU - Chen, W. H.

AU - Chang, A.

AU - Lee, I. Y.

AU - Huang, M. Y.

AU - Lee, J. T.

AU - Hsu, Y. D.

AU - Lin, C. C.

AU - Cheng, C. A.

AU - Yen, C. H.

AU - Tsai, C. K.

AU - Lee, A.

AU - Chen, C. I.

AU - Hsu, C. T.

PY - 2019/7/13

Y1 - 2019/7/13

N2 - 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. Funding: None.

AB - 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. Funding: None.

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UR - http://www.scopus.com/inward/citedby.url?scp=85068565813&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(19)31053-0

DO - 10.1016/S0140-6736(19)31053-0

M3 - Article

VL - 394

SP - 139

EP - 147

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10193

ER -