Medication May Promote Opening Of Arteries Following Stroke

Ischemic stroke, the most common type of stroke, generally occurs when a blood clot lodges in an artery, blocking blood flow to the brain. Some patients with ischemic stroke are treated quickly with intravenous recombinant tissue plasminogen activator (rtPA), which works to help dissolve the clot and reopen the artery. However, some patients do not respond to rtPA alone, according to background information in the article. In animals, argatroban--which blocks the action of chemicals that clot the blood--has been shown to work with rtPA, increasing blood flow, speeding the opening of blood vessels and preventing recurring blockages. Argatroban is approved for use in patients with heart attacks to help prevent clots but has not been tested in human stroke victims.

Rebecca M. Sugg, M.D., University of Texas--Houston Medical School, and colleagues evaluated the safety and efficacy of the drug combination in 15 stroke patients (10 men and five women, average age 61 years) who had blockages in the cerebral arteries, major blood vessels leading to the brain. Patients received the standard dose of rtPA intravenously an average of 118 minutes after their symptoms began, with the initial dose of the drug administered in one minute and the rest infused over the period of an hour. Within one hour of rtPA treatment (an average of 172 minutes after symptoms began), the patients received a large dose of argatroban followed by a continuous 48-hour infusion. Patients were watched closely for signs of excessive bleeding (hemorrhage), the most common risk associated with drugs that prevent clotting; all but one participant, who showed initial signs of hemorrhage, received the intended dose of argatroban. Blood vessel blockages were monitored using a technique known as transcranial Doppler imaging.

Two patients experienced hemorrhage with symptoms, one had asymptomatic bleeding and one died. Within two hours, the arteries completely opened (a process known as recanalization) in six patients and partially opened in four patients. Reocclusion, or the recurrence of the blockage, occurred in three of those individuals. The average scores of all the patients on scales used to measure the severity of strokes improved after treatment.

Argatroban and other similar agents have not been shown to be effective on their own, but these promising early results with combination therapy warrant further study, the authors write. "Low-dose agratroban combined with intravenous rtPA may be safe and may produce faster and more complete recanalization than does rtPA alone," they conclude. A second phase of the trial, in which 50 more patients will be enrolled, is now under way. "The equilibrium point in the assessment of the risk-benefit balance of this combined therapy can ultimately be established only in an adequately powered, blinded clinical trial with an appropriate interim monitoring for early benefit and harm," they write. (Arch Neurol. 2006;63:1057-1062. Available pre-embargo to the media at http://www.jamamedia.org.)

Dr. Grotta received grant support from Texas Biotechnology Corporation. This study was supported by a training grant from the National Institutes of Health to the University of Texas--Houston Medical School Stroke Program; a grant from the National Institute of Neurological Disorders and Stroke to the Argatroban tPA Stroke Study; and a grant from the National Institute of Neurological Disorders and Stroke to the CLOTBUST trial. Texas Biotechnology Corporation provided the argatroban.