COMPARISON OF ARGATROBAN AND HIRUDIN FOR THE REPERFUSION OF THROMBOTIC ARTERIAL-OCCLUSION BY TISSUE-PLASMINOGEN ACTIVATOR

Despite theoretical advantages of direct thrombin inhibitors, recent c linical studies failed to show the superiority of hirudin over heparin in patients with acute coronary syndromes. However, these inhibitors have important in vitro differences for the inhibition of clot-bound t hrombin that may translate into different in vivo relative efficacy. T he effects of two direct thrombin inhibitors, argatroban and hirudin, on the reperfusion of thrombotic arterial occlusion by t-PA were compa red. In anesthetized rabbits thrombotic occlusion was induced in the f emoral artery t-PA, aspirin, and various doses of argatroban (1.25, 2. 5, and 5.0 mg/kg/h) or hirudin (2.5 and 5.0 mg/kg/h) were administered (six animals in each group). Blood flow was measured for 4 hours, Ani mals treated with 2.5 mg argatroban more rapidly achieved full reperfu sion than those treated with high-dose argatroban or hirudin (P < 0.05 ). At the doses that induced comparable prolongation of bleeding time, argatroban showed a significantly faster and higher level of reperfus ion than hirudin. In animals treated with hirudin, there was a positiv e correlation between the aPTT and the mean reperfusion blood flow (r = 0.70, P < 0.05). In animals treated with argatroban, this correlatio n did not exist and the high-dose argatroban was paradoxically less ef fective in promoting thrombolysis despite greater anticoagulation effe cts. In this animal model of arterial thrombosis, argatroban was more effective than hirudin in inducing rapid, full reperfusion with t-PA. Although they are both direct thrombin inhibitors, these two agents sh owed important dose-related differences in efficacy and anticoagulant effects.