Time Extended for Thrombolytic Therapy in Acute Stroke

Stroke is not a fait accompli. In a landmark trial, the NINDS study group showed that the thrombolytic agent alteplase (aka tissue plasminogen activator, aka tPA), if given within the first 3 hours after stroke onset, significantly reduces the risk of disability at 3 months.

These data were published more than 10 years ago, but the use of alteplase in acute stroke remains shockingly low. Only about 4% of eligible stroke patients—meaning those patients with ischemic stroke who show up for medical care within a 3-hour time frame—receive the drug. Clearly healthcare performs a face plant when it comes to the treatment of stroke.

Now the window of time for alteplase therapy has been increased to 4.5 hours, given the results of a new study published in this week's NEJM. In a multicenter, placebo-controlled, double-blind European trial (N = 821), patients with ischemic stroke who received alteplase (0.9 mg/kg IV) between 3 and 4.5 hours were significantly more likely to experience a favorable outcome (modified Rankin score, 0 or 1) at 90 days (alteplase, 52.4%; placebo, 45.2%).

The rate of intracranial hemorrhage was significantly higher with alteplase than placebo (27.0% vs 17.6%), as was the rate of symptomatic hemorrhage (2.4% vs 0.2%). However, mortality rates were comparable: alteplase 7.7%; placebo, 8.4%.

In an accompanying editorial, neurologist Patrick Lyden stresses that these new results importantly extend the window of time for alteplase treatment in acute ischemic stroke, but he also urges that they are not a license to delay brain-saving therapy.