In the last issue of Medical Chronicle, we looked broadly at stroke treatment and management, using the mnemonic FAST to recognise a stroke, and types of strokes. Here we look more closely at alteplase’s use in acute ischaemic stroke (AIS).

Wahlgren et al (2007) analysed 6 483 patients from 14 countries between 2002 and 2006 for this prospective, open, monitored, observational study. Primary outcomes were symptomatic (a deterioration in National Institutes of Health stroke scale score of >or=4) intracerebral haemorrhage type 2 within 24 hours and mortality at three months. They compared mortality, the proportion of patients with symptomatic intracerebral haemorrhage as per the Cochrane definition, and functional outcome at three months with relevant pooled results from randomised controlled trials.

At 24 hours, the proportion of patients with symptomatic intracerebral haemorrhage was 1.7%. At seven days, the proportion with the same condition was 7.3% compared with 8.6% in the pooled randomised controlled trials. The mortality rate at three months in SITS-MOST was 11.3% compared with 17.3% in the pooled randomised controlled trials.

These data confirm that intravenous alteplase is safe and effective in routine clinical use when used within three hours of stroke onset, even by centres with little previous experience of thrombolytic therapy for acute stroke. The findings should encourage wider use of thrombolytic therapy for suitable patients treated in stroke centres.

Alteplase 3 to 4.5 hours after AIS

Hacke et al (2008) tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke.

They randomly assigned 821 patients with AIS in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, divided into favourable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavourable outcome (a score of 2 to 6).

More patients had a favourable outcome with alteplase than with placebo (52.4% vs 45.2%). In the global analysis, the outcome was also improved with alteplase as compared with placebo. The incidence of intracranial haemorrhage was higher with alteplase than with placebo. Mortality did not differ significantly between the alteplase and placebo groups and there was no significant difference in the rate of other serious adverse events.

Conclusion

As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischaemic stroke.

References available on request.