Alteplase: new indication. Inadequately assessed in ischaemic stroke.

(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.