Combination therapy in peripheral vascular disease:

Local thrombolysis is a well-established technique to treat arterial and venous thromboembolic disease and graft occlusions, but the utility of this approach continues to be limited by both the dose and duration of treatment required for effective clot lysis. In addition, thrombolytic therapy necessitates costly intensive care monitoring and exposing patients to the risk of bleeding. Attempts to improve the speed and efficacy of thrombolytic therapy by changing infusion protocols and catheter configurations have met with varied success. Many investigators have added mechanical thrombectomy to accelerate thrombolysis, but these methods continue to be limited by events of distal embolization; the inability to remove clot at the capillary level; and the induction of endothelial damage, which may compromise the longterm patency of treated vessels. The main elements of thrombus include fibrin, thrombin, and platelets. Current techniques to dissolve clot focus on the fibrin and thrombin components but fail to address the important effects of platelets. Our understanding of the role of the platelet in acute vascular events—including those associated with thrombolysis— has dramatically increased in the last decade. Thrombolysis may dissolve the fibrin component of the clot but may have no effect on the platelet portion. A new class of drugs has been developed that blocks the final common pathway of platelet aggregation, the glycoprotein IIb/IIIa platelet receptor. Because there is little published experience with these drugs in peripheral vascular thrombolysis, much of the rationale for using these drugs in the periphery has been extrapolated from the experience in the coronary literature when used in combination with the currently used lytic agents for thrombolysis including recombinant tissue-type plasminogen activator (rt-PA) alteplase (Activase, Genentech, South San Francisco, CA) or recombinant activator (r-PA) reteplase (Retavase, Centocor, Malvern, PA).