Intra-arterial third-generation recombinant tissue plasminogen activator (reteplase) for acute ischemic stroke

OBJECTIVE: We prospectively evaluated the safety and recanalization efficac y of intra-arterially administered reteplase, a third-generation recombinan t tissue plasminogen activator, for treating ischemic stroke in patients co nsidered poor candidates for intravenously administered alteplase therapy. METHODS: Patients were considered poor candidates for intravenously adminis tered therapy because of severity of neurological deficits, interval from o nset of symptoms to presentation of 3 hours or more, or recent major surger y. We administered a maximum total dose of 8 U of reteplase intra-arteriall y in 1-U increments via superselective catheterization. Adjunctive angiopla sty of the occluded artery was performed in seven patients. Angiographic ev idence of perfusion and thrombus was graded by use of modified Thrombolysis in Myocardial Infarction (TIMI) criteria. Neurological examinations were p erformed before and 24 hours and 7 to 10 days after treatment. RESULTS: Sixteen consecutive patients were treated (mean age, 64.1 +/- 16.4 yr; seven were men). Initial National Institutes of Health Stroke Scale sc ores ranged from 10 to 26. Time from onset of symptoms to treatment ranged from 2 to 9 hours. Occlusion sites were the cervical internal carotid arter y (n = 4), intracranial internal carotid artery (n = 4), middle cerebral ar tery (n = 6), and vertebrobasilar artery (n = 2). Complete or near-complete perfusion (TIMI Grade 3 or 4) was achieved in the arteries in 14 patients (88%), with partial recanalization (TIMI Grade 2) or minimal response (TIMI Grade 1) in the arteries in one patient each. Neurological improvement (de fined as decrease of four or more points in National Institutes of Health S troke Scale score) was observed in 7 (44%) of the 16 patients at 24 hours. Symptomatic intracerebral hemorrhage occurred in one patient; three other p atients experienced intracerebral hemorrhages that did not result in neurol ogical worsening. The overall mortality during hospitalization was 56%, rel ated to massive ischemic stroke (n = 7), withdrawal of care at the family's request after the development of aspiration pneumonia and renal failure (n = 1), and a combination of intracerebral hemorrhage and massive ischemic s troke (n = 1). CONCLUSION: In this study, intra-arterially administered reteplase in doses up to 8 U with or without angioplasty resulted in a high rate of recanaliz ation. This strategy should be considered in treating patients considered p oor candidates for intravenous thrombolysis.