Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke - The PROACT II trial

Objective: To analyze the frequency, clinical characteristics, and predicto rs of symptomatic intracerebral hemorrhage (ICH) after intraarterial (IA) t hrombolysis with recombinant pro-urokinase (r-proUK) in acute ischemic stro ke. Methods: The authors conducted an exploratory analysis of symptomatic I CH from a randomized, controlled clinical trial of IA thrombolysis with r-p roUK for patients with angiographically documented occlusion of the middle cerebral artery within 6 hours from stroke onset. Patients (n = 180) were r andomized in a ratio of 2:1 to either 9 mg IA r-proUK over 120 minutes plus IV fixed-dose heparin or IV fixed-dose heparin alone. As opposed to intent ion to treat, this analysis was based on "treatment received" and includes 110 patients given r-proUK and 64 who did not receive any thrombolytic agen t. The remaining six patients received out-of-protocol urokinase and were e xcluded from analysis. The authors analyzed centrally adjudicated ICH with associated neurologic deterioration (increase in NIH Stroke Scale [NIHSS] s core of greater than or equal to4 points) within 36 hours of treatment init iation. Results: Symptomatic ICH occurred in 12 of 110 patients (10.9%) tre ated with r-proUK and in two of 64 (3.1%) receiving heparin alone. ICH symp toms in r-proUK-treated patients occurred at a mean of 10.2 +/- 7.4 hours a fter the start of treatment. Mortality after symptomatic ICH was 83% (10/12 patients). Only blood glucose was significantly associated with symptomati c ICH in r-proUK-treated patients based on univariate analyses of 24 variab les: patients with baseline glucose > 200 mg/dL experienced a 36% risk of s ymptomatic ICH compared with 9% for those with less than or equal to 200 mg /dL (p = 0.022; relative risk, 4.2; 95% CI, 1.04 to 11.7). Conclusions: Sym ptomatic ICH after IA thrombolysis with r-proUK for acute ischemic stroke o ccurs early after treatment and has high mortality. The risk of symptomatic ICH may be increased in patients with a blood glucose > 200 mg/dL at strok e onset.