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Evidence summaries

Thrombolysis for Acute Ischaemic Stroke

Thrombolytic therapy given up to 6 hours after stroke reduces the proportion of dead or dependent people. Those treated within the first 3 hours derive substantially more benefit than with later treatment. Level of evidence: "A"

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.

    References

    • Wardlaw JM, Murray V, Berge E et al. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 2014;7():CD000213. [PubMed]
    • Wahlgren N, Ahmed N, Dávalos A, Ford GA, Grond M, Hacke W, Hennerici MG, Kaste M, Kuelkens S, Larrue V, Lees KR, Roine RO, Soinne L, Toni D, Vanhooren G, SITS-MOST investigators. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007 Jan 27;369(9558):275-82. [PubMed]

Primary/Secondary Keywords