The effect of clopidogrel, aspirin and both antiplatelet drugs on platelet function in patients with peripheral arterial disease.

Peripheral arterial disease (PAD) is associated with platelet hyperactivity. Aspirin and clopidogrel, two platelet inhibitors, act by different mechanisms. Aspirin inhibits thromboxane A 2 synthesis and clopidogrel acts on the P2Y 12 platelet ADP receptor. We evaluated the effect of clopidogrel (75 mg/day), aspirin (75 mg/day) and then both drugs on several platelet function indices in patients with PAD ( n = 20). There was a significant ( P = 0.0001) decrease in ADP-induced aggregation, after clopidogrel but not after taking aspirin. Clopidogrel plus aspirin significantly decreased spontaneous platelet aggregation (SPA) ( P = 0.01 to P = 0.002) but SPA was not significantly altered by either aspirin or clopidogrel monotherapy. Similarly, monotherapy did not inhibit serotonin (5HT)-induced aggregation but there was a significant inhibition ( P = 0.03 to P <0.02) after combination therapy. ADP (0.8 μM)-induced platelet shape change (PSC) was significantly inhibited by clopidogrel ( P = 0.004) or aspirin ( P = 0.01). This was also true for 5HT-induced PSC (clopidogrel, P = 0.01; aspirin, P = 0.03). Soluble P-selectin decreased significantly (from 32 ± 24 to 25 ± 17 ng/ml, P = 0.04) with combination therapy. Plasma platelet-derived growth factor and intraplatelet 5HT levels were not altered by combination therapy. In PAD, clopidogrel is a more potent inhibitor of ADP-induced platelet activation than aspirin; combination therapy is more effective than clopidogrel or aspirin monotherapy. These potentially clinically relevant findings should be evaluated in appropriately designed trials. [ABSTRACT FROM AUTHOR]