Aggressive mechanical clot disruption and low-dose intra-arterial third-generation thrombolytic agent for ischemic stroke: a prospective study

We prospectively evaluated the safety and effectiveness of aggressive mechanical disruption of clot in conjunction with intra-arterial administration of a low-dose third-generation thrombolytic agent (reteplase) to treat ischemic stroke in patients who were considered poor candidates for intravenous alteplase therapy or who failed to improve after intravenous thrombolysis. Mechanical clot disruption was used if low-dose pharmacological thrombolysis was ineffective. This strategy was adopted to increase the recanalization rate without increasing the risk of intracerebral hemorrhage.

Patients were considered poor candidates for intravenous therapy because of severity of neurological deficits, interval from symptom onset to presentation of at least 3 hours, or recent major surgery. We administered a maximum total dose of 4 U of reteplase intra-arterially in 1-U increments via superselective catheterization. After the initial doses were administered, we performed mechanical angioplasty (for proximal occlusion) or snare manipulation (for distal occlusion) at the occlusion site if recanalization had not occurred. The remaining doses of thrombolytics were subsequently administered if required for further recanalization. Angiographic responses were graded using modified Thrombolysis in Myocardial Infarction (TIMI) criteria. Clinical evaluations were performed before and 24 hours, 7 to 10 days, and 1 to 3 months after treatment.

Nineteen consecutive patients were treated (mean age, 64.3 +/- 16.2 yr; 10 were men). Initial National Institutes of Health Stroke Scale scores ranged from 11 to 42. Time from onset to treatment ranged from 1 to 9 hours. Occlusion sites were in the following arteries: cervical internal carotid (n = 7), intracranial internal carotid (n = 1), middle cerebral (n = 9), and basilar (n = 2). Of the 19 patients, thrombolysis alone was used in 5 patients, angioplasty was performed in 11 patients, and snare maneuvers were used in 5 patients. Complete restoration of blood flow (modified TIMI Grade 4) was observed in 12 patients, near-complete restoration of flow (modified TIMI Grade 3) in 4 patients, minimal response (modified TIMI Grade 1) in 1 patient, and no response in 2 patients (modified TIMI Grade 0). Neurological improvement at 24 hours (decline of at least 4 points in National Institutes of Health Stroke Scale score) was observed in seven patients. Five other patients experienced further improvement in National Institutes of Health Stroke Scale score at 7 to 10 days. No vessel rupture, dissection, or symptomatic intracranial hemorrhages were observed. At the time of follow-up evaluation, 7 of 19 patients were functionally independent.

A high rate of recanalization and clinical improvement can be observed in patients with ischemic stroke using low-dose thrombolytic agents with adjunctive mechanical disruption of clot. Moreover, this strategy may reduce the risk of intracerebral hemorrhage observed with thrombolytics.