Effect of Alteplase Within 6 Hours of Acute Ischemic Stroke on All-Cause Mortality (Third International Stroke Trial)

IST-3 Collaborative Grp; William N. Whiteley; Douglas Thompson; Gordon Murray; Geoff Cohen; Richard I. Lindley; Joanna Wardlaw; Peter Sandercock

doi:10.1161/STROKEAHA.114.006890

Effect of Alteplase Within 6 Hours of Acute Ischemic Stroke on All-Cause Mortality (Third International Stroke Trial)

IST-3 Collaborative Grp, William N. Whiteley^*, Douglas Thompson, Gordon Murray, Geoff Cohen, Richard I. Lindley, Joanna Wardlaw, Peter Sandercock

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

BACKGROUND AND PURPOSE: Prompt thrombolytic therapy with intravenous alteplase reduces disability after acute ischemic stroke. In an exploratory analysis, we examined whether long-term survival varied by baseline characteristics after alteplase.

METHODS: In this open-treatment, international, randomized, controlled trial, ischemic stroke patients were randomly allocated <6 hours of onset to intravenous alteplase (0.9 mg/kg) plus standard care (n=1515) or standard care alone (n=1520). We followed patients to death, censoring when last known to be alive. We grouped patients by delay to randomization, and good or poor predicted prognosis (calculated from baseline National Institutes of Health Stroke Scale [NIHSS] score and age). We present absolute mortality differences between treated and control groups at 7 days, 6 months, and 18 months poststroke.

RESULTS: Alteplase was not associated with a significant increase in mortality within 18 months (0.6% [95% confidence interval (CI), -2.9% to +4.2] P=0.72] in all patients with complete vital status (99.9%, 3034/3035). In patients randomized <3 hours of stroke, 18-month mortality was lower in the alteplase-treated group than the control group (40.6% [95% CI, 42.6-52.7] versus 47.8% [95% CI, 35.5-45.3]; P=0.0434]. The difference in 18-month mortality between alteplase-treated and control patients was greater in patients who were randomized early (<3 hours) compared with late (3-6 hours; +9% [95% CI, 1-17]; P=0.0317). Alteplase led to a greater improvement in 18-month survival in patients with a poor prognosis than in patients with a good prognosis (+8% [95% CI, 2-14]; P=0.0091).

CONCLUSIONS: These exploratory analyses of the third International Stroke Trial (IST-3) trial support improving acute stroke patients' access to earlier alteplase treatment, treatment of patients with poor prognosis, and further randomized controlled trials in minor stroke to replicate these findings.

CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25765518.

Original language	English
Pages (from-to)	3612-3617
Number of pages	6
Journal	Stroke
Volume	45
Issue number	12
DOIs	https://doi.org/10.1161/STROKEAHA.114.006890
Publication status	Published - Dec 2014

Keywords / Materials (for Non-textual outputs)

mortality
randomized controlled trial
thrombolytic therapy
TISSUE-PLASMINOGEN ACTIVATOR
RANDOMIZED CONTROLLED-TRIAL
IST-3
THROMBOLYSIS
METAANALYSIS
HEMORRHAGE

Access to Document

10.1161/STROKEAHA.114.006890

http://stroke.ahajournals.org/content/45/12/3612

The third International Stroke Trial (IST-3)
Sandercock, P. (Creator), Wardlaw, J. (Creator), Lindley, R. (Creator), Cohen, G. (Creator) & Whiteley, W. (Creator), Edinburgh DataShare, 25 Jan 2021
DOI: 10.7488/ds/1350
Dataset

William Whiteley
- Deanery of Clinical Sciences - Personal Chair of Neurology and Epidemiology
- Centre for Clinical Brain Sciences
- Edinburgh Neuroscience
- Edinburgh Imaging
- Cerebrovascular Research Group
Person: Academic: Research Active

Cite this

@article{c956af8dd93b4bd4a19b9b5442edc50d,

title = "Effect of Alteplase Within 6 Hours of Acute Ischemic Stroke on All-Cause Mortality (Third International Stroke Trial)",

abstract = "BACKGROUND AND PURPOSE: Prompt thrombolytic therapy with intravenous alteplase reduces disability after acute ischemic stroke. In an exploratory analysis, we examined whether long-term survival varied by baseline characteristics after alteplase.METHODS: In this open-treatment, international, randomized, controlled trial, ischemic stroke patients were randomly allocated <6 hours of onset to intravenous alteplase (0.9 mg/kg) plus standard care (n=1515) or standard care alone (n=1520). We followed patients to death, censoring when last known to be alive. We grouped patients by delay to randomization, and good or poor predicted prognosis (calculated from baseline National Institutes of Health Stroke Scale [NIHSS] score and age). We present absolute mortality differences between treated and control groups at 7 days, 6 months, and 18 months poststroke.RESULTS: Alteplase was not associated with a significant increase in mortality within 18 months (0.6% [95% confidence interval (CI), -2.9% to +4.2] P=0.72] in all patients with complete vital status (99.9%, 3034/3035). In patients randomized <3 hours of stroke, 18-month mortality was lower in the alteplase-treated group than the control group (40.6% [95% CI, 42.6-52.7] versus 47.8% [95% CI, 35.5-45.3]; P=0.0434]. The difference in 18-month mortality between alteplase-treated and control patients was greater in patients who were randomized early (<3 hours) compared with late (3-6 hours; +9% [95% CI, 1-17]; P=0.0317). Alteplase led to a greater improvement in 18-month survival in patients with a poor prognosis than in patients with a good prognosis (+8% [95% CI, 2-14]; P=0.0091).CONCLUSIONS: These exploratory analyses of the third International Stroke Trial (IST-3) trial support improving acute stroke patients' access to earlier alteplase treatment, treatment of patients with poor prognosis, and further randomized controlled trials in minor stroke to replicate these findings.CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25765518.",

keywords = "mortality, randomized controlled trial, thrombolytic therapy, TISSUE-PLASMINOGEN ACTIVATOR, RANDOMIZED CONTROLLED-TRIAL, IST-3, THROMBOLYSIS, METAANALYSIS, HEMORRHAGE",

author = "{IST-3 Collaborative Grp} and Whiteley, {William N.} and Douglas Thompson and Gordon Murray and Geoff Cohen and Lindley, {Richard I.} and Joanna Wardlaw and Peter Sandercock",

note = "{\textcopyright} 2014 American Heart Association, Inc.",

year = "2014",

month = dec,

doi = "10.1161/STROKEAHA.114.006890",

language = "English",

volume = "45",

pages = "3612--3617",

journal = "Stroke",

issn = "0039-2499",

publisher = "Lippincott Williams & Wilkins",

number = "12",

}

TY - JOUR

T1 - Effect of Alteplase Within 6 Hours of Acute Ischemic Stroke on All-Cause Mortality (Third International Stroke Trial)

AU - IST-3 Collaborative Grp

AU - Whiteley, William N.

AU - Thompson, Douglas

AU - Murray, Gordon

AU - Cohen, Geoff

AU - Lindley, Richard I.

AU - Wardlaw, Joanna

AU - Sandercock, Peter

PY - 2014/12

Y1 - 2014/12

N2 - BACKGROUND AND PURPOSE: Prompt thrombolytic therapy with intravenous alteplase reduces disability after acute ischemic stroke. In an exploratory analysis, we examined whether long-term survival varied by baseline characteristics after alteplase.METHODS: In this open-treatment, international, randomized, controlled trial, ischemic stroke patients were randomly allocated <6 hours of onset to intravenous alteplase (0.9 mg/kg) plus standard care (n=1515) or standard care alone (n=1520). We followed patients to death, censoring when last known to be alive. We grouped patients by delay to randomization, and good or poor predicted prognosis (calculated from baseline National Institutes of Health Stroke Scale [NIHSS] score and age). We present absolute mortality differences between treated and control groups at 7 days, 6 months, and 18 months poststroke.RESULTS: Alteplase was not associated with a significant increase in mortality within 18 months (0.6% [95% confidence interval (CI), -2.9% to +4.2] P=0.72] in all patients with complete vital status (99.9%, 3034/3035). In patients randomized <3 hours of stroke, 18-month mortality was lower in the alteplase-treated group than the control group (40.6% [95% CI, 42.6-52.7] versus 47.8% [95% CI, 35.5-45.3]; P=0.0434]. The difference in 18-month mortality between alteplase-treated and control patients was greater in patients who were randomized early (<3 hours) compared with late (3-6 hours; +9% [95% CI, 1-17]; P=0.0317). Alteplase led to a greater improvement in 18-month survival in patients with a poor prognosis than in patients with a good prognosis (+8% [95% CI, 2-14]; P=0.0091).CONCLUSIONS: These exploratory analyses of the third International Stroke Trial (IST-3) trial support improving acute stroke patients' access to earlier alteplase treatment, treatment of patients with poor prognosis, and further randomized controlled trials in minor stroke to replicate these findings.CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25765518.

AB - BACKGROUND AND PURPOSE: Prompt thrombolytic therapy with intravenous alteplase reduces disability after acute ischemic stroke. In an exploratory analysis, we examined whether long-term survival varied by baseline characteristics after alteplase.METHODS: In this open-treatment, international, randomized, controlled trial, ischemic stroke patients were randomly allocated <6 hours of onset to intravenous alteplase (0.9 mg/kg) plus standard care (n=1515) or standard care alone (n=1520). We followed patients to death, censoring when last known to be alive. We grouped patients by delay to randomization, and good or poor predicted prognosis (calculated from baseline National Institutes of Health Stroke Scale [NIHSS] score and age). We present absolute mortality differences between treated and control groups at 7 days, 6 months, and 18 months poststroke.RESULTS: Alteplase was not associated with a significant increase in mortality within 18 months (0.6% [95% confidence interval (CI), -2.9% to +4.2] P=0.72] in all patients with complete vital status (99.9%, 3034/3035). In patients randomized <3 hours of stroke, 18-month mortality was lower in the alteplase-treated group than the control group (40.6% [95% CI, 42.6-52.7] versus 47.8% [95% CI, 35.5-45.3]; P=0.0434]. The difference in 18-month mortality between alteplase-treated and control patients was greater in patients who were randomized early (<3 hours) compared with late (3-6 hours; +9% [95% CI, 1-17]; P=0.0317). Alteplase led to a greater improvement in 18-month survival in patients with a poor prognosis than in patients with a good prognosis (+8% [95% CI, 2-14]; P=0.0091).CONCLUSIONS: These exploratory analyses of the third International Stroke Trial (IST-3) trial support improving acute stroke patients' access to earlier alteplase treatment, treatment of patients with poor prognosis, and further randomized controlled trials in minor stroke to replicate these findings.CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25765518.

KW - mortality

KW - randomized controlled trial

KW - thrombolytic therapy

KW - TISSUE-PLASMINOGEN ACTIVATOR

KW - RANDOMIZED CONTROLLED-TRIAL

KW - IST-3

KW - THROMBOLYSIS

KW - METAANALYSIS

KW - HEMORRHAGE

U2 - 10.1161/STROKEAHA.114.006890

DO - 10.1161/STROKEAHA.114.006890

M3 - Article

C2 - 25370587

SN - 0039-2499

VL - 45

SP - 3612

EP - 3617

JO - Stroke

JF - Stroke

IS - 12

ER -

Effect of Alteplase Within 6 Hours of Acute Ischemic Stroke on All-Cause Mortality (Third International Stroke Trial)

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The third International Stroke Trial (IST-3)

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William Whiteley

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