The use of glycoprotein IIb/IIIa antagonists in peripheral arterial occlusion

The use of intra-arterial, catheter-directed thrombolytic therapy has been associated with the necessity to infuse the agents over a protracted period of time. The large, randomized studies suggest that most treatments require more than 24 hours of infusion. There are data to suggest that the risk of complications, especially hemorrhagic complications, increases as the duration of administration increases. Moreover, the economic burden of thrombolytic therapy increases in proportion to the length of infusion, specifically with respect to the cost of the agent and the use of hospital resources, such as the intensive care unit. For these reasons, it is desirable to formulate a treatment strategy that results in a more rapid rate of thrombolysis. Thrombolytic dissolution of an occluding thrombus is a dynamic process; new thrombus is laid down as old thrombus is dissolved. Because this process occurs in the high-flow arterial milieu, platelets are of prime importance and contribute directly to the phenomenon of rethrombosis. Platelets have also been implicated in the more chronic problems associated with smooth muscle cell and leukocyte-dependent intimal hyperplasia that culminates in restenosis at sites of arterial injury. Platelet antagonists, such as the glycoprotein IIb/IIIa inhibitors, are attractive as adjuvants to peripheral thrombolysis; the rate of thrombolysis may be increased by inhibiting new thrombus deposition. The agents may also discourage the formation of a restenotic lesion at the site of intervention. Initial studies suggest that this may indeed be the case, and there is much interest in validating the use of platelet antagonists through the performance of well-designed clinical trials.