A recent study reported potential efficacy in outcome with alteplase compared to placebo. A total of 821 patients were enrolled, with 418 randomly assigned to the alteplase group (0.9 mg/kg IV, up to 90 mg IV, with 10% by bolus and the remainder continuously infused over 1 hour) and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes.

The incidence of any intracranial hemorrhage was 27% in the alteplase group compared to 17.6% in the placebo group (P=.001). This underscores the not-uncommon finding of spontaneous hemorrhagic transformation of an initially ischemic stroke. The risk of symptomatic intracranial hemorrhage, however, was considerably lower, with 2.4% in the alteplase group versus 0.2% in the placebo group (P=.008). There was no difference in mortality.

Looking at disability at 90 days, more patients had a favorable outcome with alteplase compared to placebo (52.4% versus 45.2%, odds ratio = 1.34, P=.04). This study was impacted by the exclusion of severe stroke but did report a benefit with the extension of the alteplase window unlike the ATLANTIS study, with a 3- to 5-hour window. Also, unlike some of the previous studies of thrombolytic therapy in acute ischemic stroke, patients in this latest study were allowed to receive low dose SC heparin within the initial 24 hours in an effort to protect against the potential complication of deep venous thrombosis.

We now must see whether or not this study leads to FDA approval for extension of the therapeutic window for recombinant tissue plasminogen activator (rt-PA, alteplase) beyond the presently approved 3-hour window. This limited therapeutic window remains the greatest obstacle to the more frequent use of this agent in acute ischemic stroke.

There has been criticism that more patients are eligible for treatment than are being treated because of the fear of symptomatic intracranial hemorrhage reported at 6.4% in the pivotal NINDS study of rt-PA. However, there can be great angst among clinicians, especially those who do not frequently use rt-PA in acute stroke, when they are called in to make a potentially life or death decision with very little time to assess the pluses and minuses for a particular patient with the overriding tenet of “do no harm.”

The major take-home message of this study is that when there is some concern about the patient’s time of initial presentation, which is not at all uncommon, then giving the thrombolytic agent within a reasonable period of time beyond the 3-hour window will more likely help rather than hurt the outcome. It might allow the treating physician who is called in during the middle of the night to treat the patient, through weary eyes, to be able to sleep a bit more comfortably after the infusion is completed.

However, one must also keep in mind that larger strokes associated with more severe neurologic deficits, specifically those with an NIH Stroke Scale of 25 or higher, are best treated strictly within the 3-hour window. The risk of intracranial hemorrhage, as a complication, is probably higher but there is little else to offer in what could otherwise very well be a poor outcome without intervention.