Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations : Individual-patient-data meta-analysis of randomized trials

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Stroke Thrombolysis Trialists' 2018 , ' Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations : Individual-patient-data meta-analysis of randomized trials ' , International Journal of Stroke , vol. 13 , no. 2 , pp. 175-189 . https://doi.org/10.1177/1747493017744464

Title: Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations : Individual-patient-data meta-analysis of randomized trials
Author: Stroke Thrombolysis Trialists'
Date: 2018-02
Language: eng
Number of pages: 15
Belongs to series: International Journal of Stroke
ISSN: 1747-4930
URI: http://hdl.handle.net/10138/301083
Abstract: Background The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5h. Methods We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0-1) at 3-6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results Alteplase increased the odds of modified Rankin score 0-1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21-1.68 and 1.43, 1.23-1.65, respectively), but not in those outside the age-revised label (1.06, 0.90-1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76-1.25 and 1.01, 0.86-1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99-1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19-2.01 and 1.37, 1.17-1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97-1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77-1.26 and 1.02, 0.87-1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98-1.41). Conclusions An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.
Subject: Alteplase
acute ischemic stroke
European Union
United States
meta-analysis
rt-PA
acute stroke therapy
thrombolysis
ACUTE ISCHEMIC-STROKE
PLASMINOGEN-ACTIVATOR ALTEPLASE
INTRAVENOUS THROMBOLYSIS
GUIDELINE
THERAPY
LABEL
ECASS
IST-3
3112 Neurosciences
3124 Neurology and psychiatry
3121 General medicine, internal medicine and other clinical medicine
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