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Low-dose Reteplase with Adjunctive Mechanical Clot Disruption Appears Safe and Effective for Ischemic Strokes

Use of low-dose thrombolytic agents with adjunctive mechanical disruption of the blood clot appears to be an effective treatment for ischaemic strokes and may reduce the risk of haemorrhage associated with thrombolytic therapy.

Adnan I Qureshi, MD, and colleagues at the University at Buffalo, SUNY, School of Medicine and Biomedical Sciences, in Buffalo, New York, United States, evaluated the safety and efficacy of mechanical disruption of brain clots in conjunction with the administration of a low dose of reteplase, on ischaemic stroke patients.

The prospective study involved 19 consecutive patients, 10 men and 9 women with a mean age of 64.3 years, who were considered poor candidates for intravenous alteplase therapy or who failed to improve after intravenous thrombolysis.

Each patient received a maximum total dose of 4 U of reteplase intra-arterially in 1-U increments via superselective catheterisation. After the initial doses, the researchers performed mechanical angioplasty for proximal occlusion or snare manipulation for distal occlusion at the occlusion site, if recanalisation had not occurred. The remaining doses of thrombolytics were subsequently administered for further recanalisation, if required.

The researchers then graded the angiographic responses using modified Thrombolysis in Myocardial Infarction (TIMI) criteria and performed clinical evaluations before treatment and at 24 hours, 7 to 10 days, and 1 to 3 months after treatment.

Complete restoration of blood flow (modified TIMI Grade 4) was observed in 12 patients, the researchers report. Near-complete restoration of flow (modified TIMI Grade 3) occurred in 4 patients, minimal response (modified TIMI Grade 1) in 1 patient, and no response in 2 patients (modified TIMI Grade 0).

At 24 hours, neurological improvement (decline of at least 4 points in National Institutes of Health Stroke Scale score) was seen in 7 patients. The scores of 5 other patients improved further at 7 to 10 days.

No vessel rupture, dissection, or symptomatic intracranial haemorrhages were observed. At follow-up evaluation, 7 of 19 patients were functionally independent, the researchers note.

"A high rate of recanalisation and clinical improvement can be observed in patients with ischaemic stroke using low-dose thrombolytic agents with adjunctive mechanical disruption of clot," the researchers conclude. "Moreover, this strategy may reduce the risk of intracerebral haemorrhage observed with thrombolytics."
Neurosurgery 2002; 51: 1319-1329. "Aggressive Mechanical Clot Disruption and Low-dose Intra-arterial Third-generation Thrombolytic Agent for Ischemic Stroke: A Prospective Study."

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