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Thrombolysis for Stroke Within 4.5 Hours Is Safe and Effective

But still, the sooner treatment is administered, the better!

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."

Comment: The findings of this carefully performed study are supported by those of a large observational trial published earlier this month (JW Emerg Med Sep 15 2008), and together they signal an immediate change in practice. Evidence now clearly demonstrates that withholding thrombolytic treatment engenders greater risk than giving it at up to 4.5 hours after symptom onset. Institutions that have an acute stroke program for patient assessment and medication administration should review these studies promptly and revise protocols.

— J. Stephen Bohan, MD, MS, FACP, FACEP

Published in Journal Watch Emergency Medicine September 24, 2008

Citation(s):

Hacke W et al. for the ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008 Sep 25; 359:1317.

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• Medline abstract (Free)

Lyden P. Thrombolytic therapy for acute stroke — Not a moment to lose. N Engl J Med 2008 Sep 25; 359:1393.

• Original article (Subscription may be required)
• Medline abstract (Free)