J. M. Wardlaw



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The Cochrane Database of Systematic Reviews summarizes all the existing randomized evidence of all treatments for all diseases, so that doctors can quickly access the most up-to-date information. The trials for the Cochrane systematic review of thrombolytic therapy in acute ischemic stroke were identified from extensive searching of the literature and contact with trial investigators. Data on several prespecified outcomes (death and symptomatic intracranial hemorrhages within the first 7 to 10 days after treatment, and death and poor functional outcome at long-term follow-up) were sought in each identified randomized, controlled trial. There have thus far been 17 completed randomized, controlled trials of thrombolytic therapy versus control in 5,216 patients (including the provisional data from the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke [ATLANTIS] A and B and Recombinant Prourokinase in Acute Cerebral Thromboembolism [PROACT] II trials). Of these, eight trials tested recombinant tissue plasminogen activator (rt-PA) in 2,889 patients (56% of all data). Overall, there was an increase in the odds of death within the first 10 days (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.48 to 2.32) and symptomatic intracranial hemorrhage (OR 3.53, 95% CI 2.79 to 4.45) with thrombolysis (slightly less with rt-PA). The odds of death at the end of follow-up were also slightly increased with thrombolysis (OR 1.31, 95% CI 1.13 to 1.52), although this increase was not significant in patients receiving rt-PA. Despite this, overall there was a significant reduction in the number of patients with a poor functional outcome (combined death or dependency) at the end of follow-up (OR 0.83, 95% CI 0.73 to 0.94), which was slightly better in patients receiving rt-PA. Most of the data came from trials testing thrombolysis up to 6 hours after stroke, but the subgroup of patients treated within 3 hours showed a greater reduction in poor functional outcome with thrombolysis (OR 0.58, 95% CI 0.46 to 0.74) with a less adverse effect on death. The available data do not allow much further subgroup analysis, although there is reasonable evidence to indicate that aspirin or heparin given within 24 hours of thrombolytic therapy causes a significant increase in intracranial hemorrhage and death. It is hoped that a meta-analysis using individual patient data may be able to address the effect of thrombolysis in further specific subgroups and examine the interaction between the severity of stroke and the effect of thrombolysis.