Reduction in platelet activation by antiplatelet agents: a prospective randomised crossover trial in claudicants

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Introduction Anti-platelet therapy reduces vascular complications in patients with peripheral vascular disease (PVD) with aspirin the most commonly prescribed agent. Clopidogrel alone or in combination with aspirin may be more effective. This study investigates the effects of aspirin, clopidogrel, and combination therapy on platelet inhibition in patients with intermittent claudication. Methods 50 patients with confirmed symptomatic peripheral vascular disease will receive aspirin, clopidogrel, and combination therapies. After each 2 week course of anti-platelet therapy, platelet activation will be flow cytometrically determined by detecting platelet membrane expression of the activation markers CD62P, PAC1, fibrinogen receptor and platelet-leukocyte aggregates. Measurements will be performed after the addition of PGE1 (for control), and after platelet activation by low and high dose (0.5&5uM) ADP. Results 19 patients have completed all treatments. No differences in platelet activation marker expression between the three anti-platelet therapies were detected in the PGE1 treated control groups. With low dose ADP, expression of all activation markers was significantly lower with both clopidogrel and combination therapy compared to aspirin alone (p<0.05). With high dose ADP, clopidogrel and combination therapy significantly inhibited all markers except platelet-leukocyte aggregates compared to aspirin alone (p<0.01). No significant differences in marker expression were observed between clopidogrel and combination therapy. Conclusions Clopidogrel and combination therapy significantly inhibit platelet activation compared to aspirin in patients with PVD. No significant difference in platelet inhibition was observed between clopidogrel and combination therapy.