Background: In 1995, the two-part National Institute of Neurological Disorders and Stroke (NINDS) Recombinant Tissue Plasminogen Activator Stroke Study found that patients who were treated with tissue plasminogen activator (t-PA) within three hours after the onset of symptoms of acute ischemic stroke were at least 30 percent more likely than patients given placebo to have minimal or no disability three months after the stroke. It was unknown, however, whether the benefit would be sustained for longer periods. Methods: In the NINDS trial, a total of 624 patients with stroke were randomly assigned to receive either t-PA or placebo. We collected outcome data over a period of 12 months after the occurrence of stroke. The primary outcome measure was a 'favorable outcome,' defined as minimal or no disability as measured by the Barthel index, the modified Rankin Scale, and the Glasgow Outcome Scale. We assessed the treatment effect using a global statistic. Results: Using an intention-to-treat analysis for the combined results of the two parts of the trial at 6 months and 12 months, we found that the global statistic favored the t-PA group (odds ratio for a favorable outcome at 6 months, 1.7; 95 percent confidence interval, 1.3 to 2.3; odds ratio at 12 months, 1.7; 95 percent confidence interval, 1.2 to 2.3). The patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at 12 months than were the placebo-treated patients (absolute increase in the proportion with a favorable outcome, 11 to 13 percentage points). There was no significant difference in mortality at 12 months between the t-PA group and the placebo group (24 percent vs. 28 percent, P = 0.29). There was no interaction between the type of stroke identified at base line and treatment with respect to the long-term response. The rate of recurrent stroke at 12 months was similar in the two groups. Conclusions: During 12 months of follow-up, the patients with acute ischemic stroke who were treated with t-PA within three hours after the onset of symptoms were more likely to have minimal or no disability than the patients given placebo. These results indicate a sustained benefit of t-PA for such patients.
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