Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. The NINDS t-PA Stroke Study Group.
OBJECTIVE
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.
D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy*; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000628:therapy; D002561:Cerebrovascular Disorders / Q000188:drug therapy*; D004311:Double-Blind Method; D005544:Forecasting; D006801:Humans; D015994:Incidence; D007275:Injections, Intravenous; D008875:Middle Aged; D010960:Plasminogen Activators / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000009:adverse effects* / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator