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Am Fam Physician. 2009;80(5):516

Background: Alteplase (Activase) is currently the only approved treatment for acute ischemic stroke. Patients receiving alteplase within three hours of the onset of symptoms were at least 30 percent more likely to have favorable outcomes at three months compared with placebo. However, less than 2 percent of patients receive this treatment, mainly because of delayed admission to a stroke center. Some earlier studies have suggested that alteplase may be beneficial even if treatment is initiated after the three-hour window. Hacke and colleagues conducted a double-blind, randomized trial to examine the effects of alteplase on patients with acute ischemic stroke.

The Study: Patients 18 to 80 years of age with a clinical diagnosis of acute ischemic stroke were randomized to receive placebo or intravenous alteplase 0.9 mg per kg (maximal dose of 90 mg). Treatment was initiated between 3.0 to 4.5 hours after the onset of stroke symptoms. Computed tomography (CT) or magnetic resonance imaging (MRI) was performed before treatment and 22 to 36 hours after treatment. Neurologic impairment was monitored for 90 days after treatment was initiated.Patients were excluded if they had intracranial bleeding or an increased risk of bleeding (e.g., recent anticoagulant use, thrombocytopenia, prior stroke or serious head trauma within the preceding three months, systolic blood pressure greater than 185 mm Hg or diastolic pressure greater than 110 mm Hg, combination of previous stroke and diabetes mellitus). Patients were also excluded if CT or MRI of the brain showed a severe stroke involving more than one third of the area supplied by the middle cerebral artery. Anticoagulant therapy was prohibited, except for subcutaneous (10,000 IU or less) or low-molecular-weight heparin for deep venous thrombosis prophylaxis.

Results: Overall, 418 and 403 patients received alteplase and placebo, respectively. Patients receiving alteplase were less likely to be disabled 90 days after stroke than those receiving placebo; 52.4 versus 45.2 percent of the study groups, respectively, had favorable outcomes (odds ratio [OR] = 1.34). Patients receiving alteplase were also more likely to return to an independent lifestyle (OR = 1.28). All symptomatic intracranial hemorrhages occurred within 36 hours after treatment initiation and were more common in patients receiving alteplase than placebo (2.4 versus 0.3 percent, respectively). Three patients taking alteplase had a fatal intracranial hemorrhage versus none in the placebo group; however, overall mortality was not significantly different between the two groups.

Conclusion: Patients with acute ischemic stroke benefited from intravenous alteplase administered 3.0 to 4.5 hours after the onset of stroke symptoms. However, the authors caution that the effect of thrombolysis is time-dependent, and that patients should be treated as early as possible to maximize the chances of a positive outcome. In their words, "having more time does not mean we should be allowed to take more time."

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