A Cochrane review included 27 RCTs with 10 187 patients with acute ischaemic stroke [Abstract] 1. A total of 16% of participants were over 80 years of age. The trials tested urokinase, streptokinase, recombinant tissue plasminogen activator, recombinant pro-urokinase or desmoteplase. Four trials used intra-arterial (ia) administration, the rest used the intravenous (iv) route. About 44% of the trials (about 70% of the participants) were testing iv. rt-PA. Most data come from trials that started treatment up to 6 hours after stroke, 7 trials recruited patients after 6 hours. Thrombolytic therapy significantly reduced the proportion of patients who were dead or dependent (modified Rankin scale 3-6) at the end of follow-up, 3 to 6 months after treatment (OR 0.85, 95% CI 0.78 to 0.93; 22 trials, n=9318). This is equivalent to 41 (95% CI 20 to 60) fewer dead or dependent participants per 1000 treated. Treatment within 3 hours of stroke appeared more effective in reducing death or dependency (OR 0.66, 95% CI 0.56 to 0.79; 10 trials, n=2160) with no statistically significant adverse effect on death (OR 0.99, 95% CI 0.82 to 1.21; 11 trials, n=2187). Trials testing rt-PA showed a significant reduction in death or dependency with treatment up to 6 hours (OR 0.84, 95% CI 0.77 to 0.93; 10 trials, n=6886). Participants aged over 80 years benefited equally to those aged under 80 years, particularly if treated within 3 hours of stroke. Thrombolytic therapy increased the risk of symptomatic intracranial haemorrhage (OR 3.75, 95% CI 3.11 to 4.51; 27 trials, n=10 186), early death (OR 1.69, 95% CI 1.44 to 1.98; 13 trials, n=7458) and death by 3 to 6 months after stroke (OR 1.18, 95% CI 1.06 to 1.30; 27 trials, n=10 187). Early death after thrombolysis was mostly attributable to intracranial haemorrhage. This represented an extra 15 (95% CI 6 fewer to 30 more) deaths at the end of follow-up per 1000 participants treated with thrombolysis. One trial that tested thrombolysis plus aspirin showed an increase in deaths when both drugs were used in combination (OR 4.56, 95% CI 1.62 to 12.84; n=309).
The Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) 3 assessed the safety and efficacy of intravenous alteplase as thrombolytic therapy within the first 3 h of onset of acute ischaemic stroke. A total of 6 483 patients were recruited for this open, observational study. At 24 h, the proportion of patients with symptomatic intracerebral haemorrhage was 1.7% ( 95% CI 1.4 to 2.0) and at 7 days, 7.3% (95% CI 6.7 to 7.9) compared with 8.6% ( 95% CI 6.3 to 11.6) in the pooled randomised controlled trials. The mortality rate at 3 months in SITS-MOST was 11.3% (95% CI 10.5 to 12·1) compared with 17.3% (95% CI 14.1 to 21.1) in the pooled randomised controlled trials.
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