The current thrombolysis guidelines for acute ischaemic stroke recommend thrombolysis with alteplase initiated within 3 hours of symptom onset.  This was following the landmark findings of the 1995 National Institute of Neurological Disorders and Stroke (NINDS) study group.  The ECAS III trial (European Cooperative Acute Stroke Study), a multi-centre, randomised, placebo controlled phase 3 trial was designed to test the hypothesis that alteplase administered in patients with acute ischaemic stroke is also effective when given 3-4.5 hours post the onset of symptoms.

The primary efficacy end-point was disability at day 90. To allow comparison with published data, a post-hoc analysis of rates of symptomatic intracranial haemorrhage was also performed.

821 patients enrolled with 418 assigned to alteplase and 403 to placebo. The median time for the administration of alteplase was 3 hours and 59 minutes. Patients had a significantly better outcome with alteplase than with placebo (52.4% vs 45.2%, odds ratio 1.34, 95%CI 1.02-1.76, p=0.04). The incidence of intracranial haemorrhage was higher with alteplase than for placebo (27% vs 17.6%, p=0.001) however mortality did not significantly differ between the 2 groups.

The potential for neurological recovery declines with every minute from symptom onset to administration of thrombolytics. This study does not suggest that the ideal window for thrombolytics administration is after 4.5 hours – from the moment that the patient arrives at the hospital door the only delay should be for brain imaging studies and possibly some basic laboratory tests. The focus must remain on rapid door to needle times. Limitations of the study include the low numbers of diabetic patients enrolled and the exclusion of patients with severe stroke.

• Hacke W, Kaste M, Bluhmki E etal. Thrombolysis with alteplase 3 to 4.5 Hours after Acute Ischaemic Stroke. N Engl J Med 2008;359:1317-29

• Lyden P (ed). Thrombolytic Therapy for Acute Stroke – Not a Moment to Lose. N Engl J Med 2008;359:1393-4