A Cochrane review [Abstract] 1 included 20 studies with a total of 2527 subjects with acute stroke. Different doses (of tissue plasminogen activator, urokinase, desmoteplase or tenecteplase) were compared in 13 trials (n=1433). Different agents (tissue plasminogen activator vs. urokinase, tissue-cultured urokinase vs. conventional urokinase, tenecteplase vs. tissue plasminogen activator) were compared in 5 trials (n=875). Five trials (n=485) compared different routes of administration. As some trials compared different agents and different doses, some patients contributed to two analyses. There was an approximately three-fold increase in fatal intracranial haemorrhages in patients allocated to higher than to lower doses (the doses varied between the trials) of the same thrombolytic drug (OR 2.71, 95% CI 1.22 to 6.04; 10 trials, n=1274). However, there was no difference in the number of patients who were dead or dependent at the end of follow-up between those allocated higher or lower doses of thrombolytic drug (OR 0.86, 95% CI 0.62 to 1.19; 7 trials, n=630). Higher vs. lower doses of desmoteplase were associated with more deaths at the end of follow-up (OR 3.21, 95% CI 1.23 to 8.39; 2 trials, n=152). There was no evidence of any benefit for intra-arterial over iv. treatment.
Comment: The quality of the evidence is downgraded by study quality (unclear allocation concealment), inconsistency (heterogeneity in interventions), indirectness of evidence (differences in treatments: many thrombolysis regimens did not represent the current standards of care) and imprecise results (small sample size in trials).
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