Background and Purpose—Because of the risk of hemorrhage, especially in the brain, thrombolytic therapy with intravenous alteplase is restricted by guidelines, and only a small number of selected patients are being treated. Findings from metaanalyses, post hoc analyses of the randomized trials, and postlicensing experience suggest that more subjects, who otherwise have a poor predicted outcome without treatment, might benefit from intravenous alteplase.

Summary of Review—There is a strong indication that treatment may still be beneficial beyond 3 hours up until 4.5 hours. The risk of symptomatic intracerebral hemorrhage is not increased in patients aged 80 years or older. Excluding patients with severe stroke or with early ischemic changes in more than one third of the middle cerebral artery territory on baseline CT scan is probably not necessary when treatment is started <3 hours of symptom onset. Patients with minor or improving symptoms can also benefit. Intravenous thrombolysis appears appropriate as first line therapy for posterior circulation stroke. Alteplase can be given to patients with cervical artery dissection, seizure at onset and evidence of acute ischemia on brain imaging, and after carefully weighing risk and benefit in pregnancy and during menstruation. There are anecdotal reports on its use in children, patients with recent myocardial infarction, cardiac embolus, intracranial aneurysm or arteriovenous malformation, prior stroke and recent surgery. There appears to be a substantially increased risk of symptomatic cerebral hemorrhage in hyperglycemic stroke patients. The combined intravenous and intraarterial approach to recanalization appears safe and is currently under investigation in a randomized trial.

Conclusions—This document does not intend to change the guidelines but reviews the literature on the use of intravenous alteplase for stroke beyond guidelines and in particular conditions.