Antithrombotic Therapy in Peripheral Arterial Occlusive Disease: Clopidogrel
Clopidogrel is a new thienopyridine, the chemical structure of which is similar to ticlopidine, that exerts an irreversible antiplatelet effect that is primarily directed against adenosine diphosphate-induced stimulation of platelet function. In a multicenter, randomized clinical trial of 19,185 patients (level I), the relative efficacy of clopidogrel was compared to aspirin in reducing the risk of a composite end point of ischemic stroke, MI, or vascular death. The study population was comprised of patients with recent ischemic stroke, recent MI, or symptomatic peripheral arterial disease. The overall incidence of composite end points was lower in the group treated with clopidogrel (5.32% per yr) than with aspirin (5.83%; p = 0.043). Particularly noteworthy is that subgroup analysis revealed that virtually all of the benefit in the study associated with clopidogrel was observed in the group with symptomatic peripheral vascular disease, who as a group sustained significantly fewer Mis and vascular-related deaths than did the aspirin-treated group. Additional studies, particularly ones that specifically address peripheral vascular disease, are needed to define the role of clopidogrel in the treatment of these patients.
Prostaglandins with antiplatelet and vasodilatory effects, such as prostaglandin Ex (PGE1) and prostaglandin I2 (PGI2), have been administered IV or intra-arterially to patients with advanced chronic arterial insufficiency in hopes of relieving rest pain and healing ischemic ulcers. PGEjl was found to be ineffective in a randomized, double-blind, multicenter trial (level II) this canadian family pharmacy online. Selective intra-arterial PGI2 was found to relieve rest pain and promote healing of ulcers to a significantly greater degree than did placebo treatment in 30 nondiabetic patients, half of whom had thromboangiitis obliterans (Buerger’s disease) (level II). However, this route of administration is impractical and may cause complications, and these results have not been confirmed in patients suffering from pure atherosclerotic arterial insufficiency. In another doubleblind trial (level II), PGI2 given IV to nondiabetic patients with severe arterial insufficiency produced significantly greater relief of rest pain than did placebo. Relief lasted up to 1 month, was not correlated with changes in ankle/brachial pressure indexes, and was not associated with ulcer healing. PGI2 administered IV was evaluated in a double-blind trial that contained a high proportion of diabetics (level II) and the results were disappointing in that PGI2 had no beneficial effect on ulcer healing or rest pain. Thus, it appears that PGI2 may provide temporary relief of rest pain in nondiabetic patients with severe arterial insufficiency and may promote healing of ischemic ulcers when given intra-arterially. However, it is doubtful that such therapy will ultimately prevent amputation in patients with end-stage, nonreconstructible vascular disease. In a recent small, randomized open study (level II), PGEX administered IV and combined with an intensive exercise regimen produced dramatic and sustained improvement in symptom-free walking distance in comparison with exercise alone or exercise combined with IV-administered pentoxifylline.