• M Liu and J Wardlaw.
• Neurosciences Trials Unit, Department of Clinical Neurosciences, Western General Hospital, Crewe Road, Edinburgh, UK, EH4 2XU. jmw@skull.dcn.ed.ac.uk
• Cochrane Db Syst Rev. 2000 Jan 1 (2): CD000514.

BackgroundThrombolytic therapy is effective for acute myocardial infarction, a vascular disease with some similarities to acute ischaemic stroke.ObjectivesThe objective of this review was to assess the effect of different thrombolytic agents, and different regimens in acute ischaemic stroke.Search StrategyWe 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 CriteriaRandomised 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 AnalysisTwo reviewers independently assessed eligibility, trial quality and extracted the data.Main ResultsEight 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 ConclusionsThere 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.

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