Overview of Cochrane thrombolysis meta-analysis

The Cochrane Database of Systematic Reviews summarizes all the existing ran domized evidence of all treatments for all diseases, so that doctors can qu ickly access the most up-to-date information. The trials for the Cochrane s ystematic review of thrombolytic therapy in acute ischemic stroke were iden tified from extensive searching of the literature and contact with trial in vestigators. Data on several prespecified outcomes (death and symptomatic i ntracranial hemorrhages within the first 7 to 10 days after treatment, and death and poor functional outcome at long-term follow-up) were sought in ea ch identified randomized, controlled trial. There have thus far been 17 com pleted randomized, controlled trials of thrombolytic therapy versus control in 5,216 patients (including the provisional data from the Alteplase Throm bolysis for Acute Noninterventional Therapy in Ischemic Stroke [ATLANTIS] A and B and Recombinant Prourokinase in Acute Cerebral Thromboembolism [PROA CT] II trials). Of these, eight trials tested recombinant tissue plasminoge n 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 intracran ial hemorrhage (OR 3.53, 95% CI 2.79 to 4.45) with thrombolysis (slightly l ess with rt-PA). The odds of death at the end of follow-up were also slight ly increased with thrombolysis (OR 1.31, 95% CI 1.13 to 1.52), although thi s increase was not significant in patients receiving rt-PA. Despite this, o verall there was a significant reduction in the number of patients with a p oor 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 re ceiving 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 availa ble data do not allow much further subgroup analysis, although there is rea sonable evidence to indicate that aspirin or heparin given within 24 hours of thrombolytic therapy causes a significant increase in intracranial hemor rhage 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 th e effect of thrombolysis.