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Thrombolysis for acute ischaemic stroke
#MMPMID25072528
Wardlaw JM
; Murray V
; Berge E
; del Zoppo GJ
Cochrane Database Syst Rev
2014[Jul]; 2014
(7
): CD000213
PMID25072528
show ga
BACKGROUND: Most strokes are due to blockage of an artery in the brain by a blood
clot. Prompt treatment with thrombolytic drugs can restore blood flow before
major brain damage has occurred and improve recovery after stroke in some people.
Thrombolytic drugs, however, can also cause serious bleeding in the brain, which
can be fatal. One drug, recombinant tissue plasminogen activator (rt-PA), is
licensed for use in selected patients within 4.5 hours of stroke in Europe and
within three hours in the USA. There is an upper age limit of 80 years in some
countries, and a limitation to mainly non-severe stroke in others. Forty per cent
more data are available since this review was last updated in 2009. OBJECTIVES:
To determine whether, and in what circumstances, thrombolytic therapy might be an
effective and safe treatment for acute ischaemic stroke. SEARCH METHODS: We
searched the Cochrane Stroke Group Trials Register (last searched November 2013),
MEDLINE (1966 to November 2013) and EMBASE (1980 to November 2013). We also
handsearched conference proceedings and journals, searched reference lists and
contacted pharmaceutical companies and trialists. SELECTION CRITERIA: Randomised
trials of any thrombolytic agent compared with control in people with definite
ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors applied the
inclusion criteria, extracted data and assessed trial quality. We verified the
extracted data with investigators of all major trials, obtaining additional
unpublished data if available. MAIN RESULTS: We included 27 trials, involving
10,187 participants, testing urokinase, streptokinase, rt-PA, recombinant
pro-urokinase or desmoteplase. Four trials used intra-arterial administration,
while the rest used the intravenous route. Most data come from trials that
started treatment up to six hours after stroke. About 44% of the trials (about
70% of the participants) were testing intravenous rt-PA. In earlier studies very
few of the participants (0.5%) were aged over 80 years; in this update, 16% of
participants are over 80 years of age due to the inclusion of IST-3 (53% of
participants in this trial were aged over 80 years). Trials published more
recently utilised computerised randomisation, so there are less likely to be
baseline imbalances than in previous versions of the review. More than 50% of
trials fulfilled criteria for high-grade concealment; there were few losses to
follow-up for the main outcomes.Thrombolytic therapy, mostly administered up to
six hours after ischaemic stroke, significantly reduced the proportion of
participants who were dead or dependent (modified Rankin 3 to 6) at three to six
months after stroke (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.78 to
0.93). Thrombolytic therapy increased the risk of symptomatic intracranial
haemorrhage (OR 3.75, 95% CI 3.11 to 4.51), early death (OR 1.69, 95% CI 1.44 to
1.98; 13 trials, 7458 participants) and death by three to six months after stroke
(OR 1.18, 95% CI 1.06 to 1.30). Early death after thrombolysis was mostly
attributable to intracranial haemorrhage. Treatment within three hours of stroke
was more effective in reducing death or dependency (OR 0.66, 95% CI 0.56 to 0.79)
without any increase in death (OR 0.99, 95% CI 0.82 to 1.21; 11 trials, 2187
participants). There was heterogeneity between the trials. Contemporaneous
antithrombotic drugs increased the risk of death. Trials testing rt-PA showed a
significant reduction in death or dependency with treatment up to six hours (OR
0.84, 95% CI 0.77 to 0.93, P = 0.0006; 8 trials, 6729 participants) with
significant heterogeneity; treatment within three hours was more beneficial (OR
0.65, 95% CI 0.54 to 0.80, P < 0.0001; 6 trials, 1779 participants) without
heterogeneity. Participants aged over 80 years benefited equally to those aged
under 80 years, particularly if treated within three hours of stroke. AUTHORS'
CONCLUSIONS: Thrombolytic therapy given up to six hours after stroke reduces the
proportion of dead or dependent people. Those treated within the first three
hours derive substantially more benefit than with later treatment. This overall
benefit was apparent despite an increase in symptomatic intracranial haemorrhage,
deaths at seven to 10 days, and deaths at final follow-up (except for trials
testing rt-PA, which had no effect on death at final follow-up). Further trials
are needed to identify the latest time window, whether people with mild stroke
benefit from thrombolysis, to find ways of reducing symptomatic intracranial
haemorrhage and deaths, and to identify the environment in which thrombolysis may
best be given in routine practice.
|*Thrombolytic Therapy/adverse effects
[MESH]
|Brain Ischemia/drug therapy
[MESH]
|Drug Administration Schedule
[MESH]
|Fibrinolytic Agents/adverse effects/*therapeutic use
[MESH]
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