Thrombolysis for Stroke Within 4.5 Hours Is Safe and Effective

Current recommendations for treatment of acute stroke require thrombolytic therapy to be given within 3 hours after symptom onset. Some previously published studies have shown a trend toward favorable outcomes with later treatment, but even in pooled analyses the findings were inconclusive. In the multinational (130 sites in 19 countries), industry-sponsored, double-blind European Cooperative Acute Stroke Study (ECASS III), investigators randomized 821 patients with stroke to treatment with either alteplase (0.9 mg/kg) or placebo at 3 to 4.5 hours after symptom onset. The primary endpoint was disability at 90 days, assessed on the modified Rankin scale and dichotomized as a favorable outcome (score of 0 or 1, representing no or minimal disability) or an unfavorable outcome (score of 2–6, with 6 representing death). The secondary endpoint was a global outcome of scores on four stroke scales. Patients with intracranial hemorrhage or severe ischemic stroke (NIHSS score >25) before treatment were excluded.

The median time to treatment was 3 hours, 59 minutes. Significantly more patients who were treated with alteplase than with placebo had favorable outcomes (52.4% vs. 45.2%; odds ratio, 1.34). The number needed to treat was 14. A significant difference in favor of alteplase also was shown for the secondary endpoint and in an intention-to-treat analysis. Intracranial hemorrhage after treatment was significantly more common in the alteplase group than in the placebo group (27.0% vs. 17.6%), but death rates did not differ between groups.

The authors and an editorialist strongly emphasize that this result is not a reason to delay treatment for even 1 minute. The editorialist notes that “every minute matters” during stroke treatment and that a more leisurely approach would be “wrong.”