Author(s): del Zoppo GJ, Higashida RT, Furlan AJ, Pessin MS, Rowley HA, , del Zoppo GJ, Higashida RT, Furlan AJ, Pessin MS, Rowley HA,
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Abstract BACKGROUND AND PURPOSE: To test the safety and recanalization efficacy of intra-arterial local delivery of plasminogen activators in acute ischemic stroke, a randomized trial of recombinant pro-urokinase (rpro-UK) versus placebo was undertaken in patients with angiographically documented proximal middle cerebral artery occlusion. METHODS: After exclusion of intracranial hemorrhage by CT scan, patients with abrupt onset of symptoms of focal ischemia likely to receive treatment within 6 hours who satisfied all clinical eligibility criteria underwent carotid angiography. Patients displaying Thrombolysis in Acute Myocardial Infarction grade 0 or 1 occlusion of the M1 or M2 middle cerebral artery were randomized 2:1 to receive rpro-UK (6 mg) or placebo over 120 minutes into the proximal thrombus face. All patients received intravenous heparin. Recanalization efficacy was assessed at the end of the 2-hour infusion, and intracerebral hemorrhage causing neurological deterioration was assessed at 24 hours. RESULTS: Of 105 patients who underwent angiography, 59 were excluded from randomization. Among the 46 patients randomized, 40 were treated with rpro-UK (n=26) or placebo (n=14) a median of 5.5 hours from symptom onset. Recanalization was significantly associated with rpro-UK (2P=.017). Hemorrhagic transformation causing neurological deterioration within 24 hours of treatment occurred in 15.4\% of the rpro-UK-treated patients and 7.1\% of the placebo-treated patients (2P=.64). Both recanalization and hemorrhage frequencies were influenced by heparin dose. CONCLUSIONS: Intra-arterial local rpro-UK infusion was associated with superior recanalization in acute thrombotic/ thromboembolic stroke compared with placebo. In this regimen, heparin dose influenced hemorrhage frequency and recanalization. Although symptomatic hemorrhage remains a concern, this study suggests that recanalization is enhanced with rpro-UK and heparin.
This article was published in Stroke
and referenced in Cardiovascular Pharmacology: Open Access