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Thrombolysis with Alteplase 3 to 4.5 Hours After Acute Ischemic Stroke

2008; Elsevier BV; Volume: 48; Issue: 6 Linguagem: Inglês

10.1016/j.jvs.2008.10.047

1097-6809

W. Hacke, M. Kaste, E. Bluhmki,

Stroke Rehabilitation and Recovery

Conclusion: Intravenous alteplase administered between 3 and 4.5 hours after onset of neurologic symptoms improves clinical outcomes in patients with acute ischemic stroke. Summary: The only approved treatment for acute ischemic stroke is intravenous thrombolysis with alteplase. Approval is for administration <3 hours after onset of symptoms. Efficacy has not been established for administration after 3 hours following onset of neurologic symptoms in patients with stroke. In this study the authors tested safety and efficacy of alteplase when given 3 to 4.5 hours after onset of stroke. Patients underwent a computed tomography scan. Those with brain hemorrhage or major infarction were excluded. The remaining patients were randomly assigned in a 1-to-1 double-blind fashion to receive treatment with placebo or intravenous alteplase at a dose of 0.9 mg/kg. The primary end point was disability at 90 days. The end point was dichotomized as a favorable or unfavorable outcome using the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms and 6 indicating death. A favorable outcome was a score of 0 or 1 and an unfavorable outcome was considered a score of 2 to 6. A secondary end point was an outcome analysis using four combined disability and neurologic scores. Death, symptomatic intracranial hemorrhage, and other serious adverse events were safety end points. The study enrolled 821 patients, with 418 randomized to the alteplase group and 403 to the placebo group. Median time for admission of alteplase was 3 hours 59 minutes. Patients treated with alteplase had more favorable outcomes than those treated with placebo, at 52.4% vs 45.2% (odds ratio, 1.24; 95% confidence interval [CI], 1.02-1.76; P = .04). Outcome was also improved in the global analysis (odds ratio, 1.28; 95% CI, 1.00-1.65; P < .05). There was a high incidence of any intracranial hemorrhage with alteplase (27% vs 17.6%; P = .01) and a higher incidence for symptomatic intracranial hemorrhage with alteplase (2.4% vs 0.2%; P = .008). Mortality did not differ between the alteplase and placebo groups (7.7% vs 8.4%; P = .68), nor was a significant difference noted in the rate of other serious adverse events. Comment: Early treatment of patients with ischemic stroke is essential, and there is a time-dependent effect of thrombolysis. This is now the second randomized trial to show treatment benefit with intravenous alteplase in patients with acute ischemic stroke. Although the risk of symptomatic intracranial hemorrhage is increased with alteplase; surprisingly, mortality is not affected. The study should not be regarded as endorsing a larger time window for beginning thrombolysis in patients with acute ischemic stroke. Treatment with alteplase is nearly twice as effective when administered within <1.5 hours than when administered between 1.5 to 3 hours after onset of symptoms. (In this study the odds ratio for favorable treatment was 1.34 when the interval to treatment was between 181 to 270 minutes.) Given the more favorable treatment effect with more rapid administration of alteplase, practitioners should still strive to administer the drug as early as possible. As the authors state: “Having more time does not mean we should be allowed to take more time.”