Treatment with intravenous recombinant tissue plasminogen activator plus argatroban may be more effective than plasminogen activator alone in restoring blood flow after an ischemic stroke, according to an article in the August issue of Archives of Neurology.

Some patients with ischemic stroke are treated quickly with intravenous recombinant tissue plasminogen activator (rtPA). However, some patients do not respond to rtPA alone, according to background information in the article.

In animals, argatroban, a direct thrombin inhibitor. has been shown to work collaboratively to improve blood flow and prevent recurrent clot. Argatroban is approved for use in patients with acute myocardial infarction but has not been tested in human stroke victims.

Rebecca M. Sugg, MD, University of Texas?Houston Medical School, and colleagues evaluated the safety and efficacy of the drug combination in 15 stroke patients (10 men and 5 women, average age 61 years) who had blockages in the cerebral arteries. Patients received the standard dose of rtPA intravenously an average of 118 minutes after symptoms began, with the initial dose administered in one minute and the rest infused over 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 hemorrhage; all but one participant, who showed initial signs of hemorrhage, received the intended dose of argatroban. Blood flow was monitored with transcranial Doppler imaging.

Two patients experienced hemorrhage: One had asymptomatic bleeding and one died. Within two hours, arteries were completely recanalized in six patients and partially opened in four patients. Reocclusion 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, according to the authors: “Low-dose argatroban combined with intravenous rtPA may be safe and may produce faster and more complete recanalization than does rtPA alone.”

A second phase of the trial, in which 50 more patients will be enrolled, is now underway. “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 concluded.