(1) Alteplase is the first thrombolytic drug to be approved in France for the 
treatment of ischaemic stroke within three hours of symptom onset. (2) The 
clinical evaluation dossier contains nine placebo-controlled trials, of which 
six were relatively large. In the two NINDS trials (624 patients in total), 
treatment was started within the first three hours and it showed no survival 
benefit. Near-complete functional recovery was more frequent in the alteplase 
group than in the placebo group. In the two ECASS trials (620 and 800 patients) 
and the ATLANTIS trials (142 patients and 613 patients), treatment was started 
within the first six hours and it showed no significant benefit in terms of 
survival or functional recovery. (3) There are two meta-analyses of these 
trials. They confirm the lack of a survival benefit with alteplase. Using a 
combined endpoint, one meta-analysis showed that treating 1000 patients with 
alteplase prevented death or major disability (dependency) in 55 patients. The 
other meta-analysis underlined the importance of a short interval between the 
onset of symptoms and the beginning of treatment. (4) Intracranial haemorrhage 
is the most important adverse effect. One meta-analysis showed that alteplase 
caused 62 additional symptomatic intracranial haemorrhages (including 25 deaths) 
per 1000 treated patients. (5) Various retrospective subgroup analyses have 
tentatively identified subgroups of patients at a particularly high risk of 
adverse effects, but subgroup analyses provide only weak evidence. The patients 
most likely to benefit from alteplase, started within three hours of symptom 
onset, remain to be defined. (6) The current health infrastructure in France 
would allow only a small number of stroke patients to be treated with alteplase 
under the kind of conditions prevailing in clinical trials (imaging to confirm 
ischaemic stroke, and treatment very soon after the onset of symptoms). (7) In 
practice, there is a narrow margin between the wanted and unwanted effects of 
alteplase. This treatment should be used only by specialised teams and for 
strictly selected patients. Research must continue, particularly to identify 
those patients most likely to benefit from alteplase, and those most likely to 
be harmed in whom thrombolysis is contraindicated.