Effect of the thrombin inhibitor argatroban in acute cerebral thrombosis

Argatroban is a direct antithrombin agent developed for the first time by Okamoto et al in 1978. Unlike heparin, it manifests its anticoagulant effect by binding directly to the active site of thrombin. A phase II double-blind comparative study was conducted in 52 facilities with a placebo control. The drug was administered by a slow intravenous infusion at 60 mg/d for the first 2 days and then at 10 mg twice daily for the subsequent 5 days. Glycerol was used concomitantly as a basic therapy for both the argatroban and placebo groups. The results demonstrated superior improvements, particularly in neurological symptoms (motor paralysis) and daily living activities (walking, standing up, continuous sitting, and eating), in the argatroban group compared with the placebo group. These improvements were observed from the early stage of administration. It was also found that administration of the drug in the early stage of the disease gave better results. In the present study, although a hemorrhagic cerebral infarct occurred in one case in the argatroban group, this seemed to be no different from a spontaneous incidence, as it also occurred in two cases in the placebo group. Symptoms were not aggravated in any of the cases. These results indicate that argatroban is an effective and safe drug for the treatment of acute cerebral thrombosis.