NEW YORK (Reuters Health) – Alteplase can improve stroke outcomes even when it is not given until 3 to 4.5 hours after the stroke began, according to a report in The New England Journal of Medicine for September 25.

Alteplase may raise the risk of symptomatic intracranial hemorrhage, but there was no increase in mortality, the report indicates.

Alteplase, begun within 3 hours of symptom onset, is the only agent currently approved for treating acute ischemic strokes, Dr. Werner Hacke, from Universitat Heidelberg in Germany, and colleagues note. The drug’s safety and efficacy beyond this treatment window has not been established.

In the current investigation, 821 stroke patients were randomized to receive intravenous alteplase (0.9 mg/kg of body weight) or placebo between 3 and 4.5 hours after symptom onset. All of the subjects had already undergone CT evaluation and had no evidence of brain hemorrhage or major infarction.

The main endpoint was a favorable disability outcome, defined as a score of 0 or 1 (0 = no symptoms, 6 = death) on the modified Rankin scale at 90 days.

The median time until alteplase administration was 3 hours and 59 minutes, the report indicates. Overall, 52.4% of alteplase-treated patients had a favorable outcome compared with 45.2% of those given placebo (p = 0.04). Global analysis, which combined four neurologic and disability scores, also indicated a significant advantage with alteplase.

Intracranial hemorrhage was more common with alteplase than with placebo: 27.0% vs. 17.6% (p = 0.001). The corresponding rates for symptomatic hemorrhage were 2.4% and 0.2% (p = 0.008). As noted, mortality rates in each group were comparable, hovering around 8%.

Aside from hemorrhage, no significant differences in serious adverse events were noted between the groups.

Despite these findings, the authors emphasize that in giving alteplase, earlier is still better.

“Although our findings suggest that treatment with alteplase may be effective in patients who present 3 to 4.5 hours after the onset of stroke symptoms, patients should be treated with alteplase as early as possible to maximize the benefit. Having more time does not mean we should be allowed to take more time.”

Reference:
N Engl J Med 2008;359:1317-1329.