Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. The NINDS t-PA Stroke Study Group.

BACKGROUND AND PURPOSE: We sought to identify variables associated with intracerebral hemorrhage in patients with acute ischemic stroke who receive tissue plasminogen activator (t-PA).

METHODS: We performed subgroup analyses of data from a randomized, double-blind, placebo-controlled trial of intravenous t-PA administered to stroke patients within 3 hours of onset. Using multivariable regression modeling procedures, we assessed the relationship of baseline and after-treatment variables with symptomatic and asymptomatic intracerebral hemorrhage during the first 36 hours after treatment.

RESULTS: Overall, t-PA-treated patients had an increase in the absolute risk of symptomatic intracerebral hemorrhage of 6% and a decrease in the absolute risk of 3-month mortality of 4% compared with placebo-treated patients. The only variables independently associated with an increased risk of symptomatic intracerebral hemorrhage in the final multivariable logistic regression model for the 312 t-PA-treated patients were the severity of neurological deficit as measured by the National Institutes of Health Stroke Scale score (five categories; odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2 to 2.9) and brain edema (defined as acute hypodensity) or mass effect by CT before treatment (OR, 7.8; 95% CI, 2.2 to 27.1). This final model correctly predicted those t-PA-treated patients who would or would not have a symptomatic hemorrhage with only 57% efficiency. In the subgroup of patients with a severe neurological deficit, t-PA-treated patients were more likely than placebo-treated patients to have a favorable 3-month outcome (adjusted OR based on multiple outcomes, 4.3; 95% CI, 1.6 to 11.9). These results were similar for the subgroup with edema or mass effect by CT (adjusted OR, 3.4; 95% CI, 0.6 to 20.7). The likelihood of severe disability or death was similar for t-PA- and placebo-treated patients with these two baseline characteristics.

CONCLUSIONS: Despite a higher rate of intracerebral hemorrhage, patients with severe strokes or edema or mass effect on the baseline-CT are reasonable candidates for t-PA, if it is administered within 3 hours of onset.