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Thrombolysis (different doses, routes of administration and agents) for acute ischaemic stroke
1Neurosciences Trials Unit, Department of Clinical Neurosciences, Western General Hospital, Crewe Road, Edinburgh, UK, EH4 2XU. jmw@skull.dcn.ed.ac.uk
Insights
Higher doses of thrombolytic therapy for acute ischemic stroke increased fatal intracranial hemorrhages. More research is needed to determine optimal thrombolytic agent doses and types for stroke treatment.
Area of Science:
- Neurology
- Vascular Medicine
Background:
- Thrombolytic therapy is a proven treatment for acute myocardial infarction.
- Acute ischemic stroke shares vascular similarities with myocardial infarction.
Purpose of the Study:
- To review the efficacy and safety of various thrombolytic agents and regimens for acute ischemic stroke.
- To compare different doses, agents, and routes of administration for thrombolytic therapy in stroke patients.
Main Methods:
- Systematic review of randomized and quasi-randomized controlled trials.
- Searched Cochrane Stroke Group trials register, Embase, and handsearched Japanese and Chinese journals.
- Included trials with treatment initiated within 14 days of stroke onset.
Main Results:
- Eight trials involving 1334 patients were analyzed, primarily conducted in Japan.
- Higher doses of thrombolytic therapy significantly increased the risk of fatal intracranial hemorrhage (OR 5.02).
- No significant differences were found between different thrombolytic agents or in non-fatal outcomes.
Conclusions:
- Insufficient evidence exists to determine optimal thrombolytic agent doses or types for acute ischemic stroke.
- Further research is required to establish the safety and effectiveness of different thrombolytic strategies.
- Comparative data for streptokinase in acute ischemic stroke treatment were not identified.
Background:
Thrombolytic therapy is effective for acute myocardial infarction, a vascular disease with some similarities to acute ischaemic stroke.
Objectives:
The objective of this review was to assess the effect of different thrombolytic agents, and different regimens in acute ischaemic stroke.
Search Strategy:
We searched the Cochrane Stroke Group trials register and Embase (1980 to 1997). We handsearched Japanese and Chinese journals. We contacted researchers in the field and pharmaceutical companies.
Selection Criteria:
Randomised and quasi-randomised trials of different doses of a thrombolytic agent, or one thrombolytic agent compared with another, or the same agent given by different routes, in people with confirmed acute ischaemic stroke. Trials were included if treatment was started within 14 days of stroke onset.
Data Collection And Analysis:
Two reviewers independently assessed eligibility, trial quality and extracted the data.
Main Results:
Eight trials involving 1334 people were included. Concealment of allocation was generally adequate. All the trials were conducted in Japan. Different doses (of tissue plasminogen activator or urokinase) were compared in seven trials. Different agents (tissue plasminogen activator versus urokinase, or tissue-cultured urokinase versus conventional urokinase) were compared in three trials. Few data were available for functional outcomes. A higher dose of thrombolytic therapy was associated with a five-fold increase in fatal intracranial haemorrhages (odds ratio 5.02, 95% confidence interval 1.56 to 16. 18). This was based on 11 events among 369 higher-dose patients and one event among 356 lower-dose patients in six trials. There was a non-significant trend towards more early deaths or clinically significant intracranial haemorrhages. No difference in late deaths or extra-cranial haemorrhages was shown between low and higher doses. However, very few of these events occurred. No difference was shown between the different thrombolytic agents tested.
Reviewer'S Conclusions:
There is not enough evidence to conclude whether lower doses of thrombolytic agents might be safer or more effective than higher doses in acute ischaemic stroke. It is not possible to conclude whether one agent might be better than another, or which route of administration might be best. No comparative data for streptokinase have been found.