The Effect of a Loading Dose (300 mg) of Clopidogrel on Platelet Function in Patients with Peripheral Arterial Disease

Abstract

Clopidogrel acts on the P2Y₁₂ adenosine diphosphate (ADP) purinergic receptors on human platelets. The aim of this study was to establish if a loading dose of clopidogrel inhibits platelet activation in patients with peripheral arterial disease (PAD). Two indices of platelet activation were considered: platelet shape change (PSC) and aggregation. Citrated blood was collected from ten PAD patients who were not on aspirin, at baseline (0 hours) and 2 and 4 hours after these patients ingested a loading dose (300 mg) of clopidogrel. ADP (5,mol/L)-induced platelet aggregation in whole blood was inhibited after 2 hours (free platelet count, 47% ± 19% vs. 68% ± 15%; p < 0.001) and 4 hours (47% ± 19% vs. 66% ± 16%; p 5 0.001). There was also a significant inhibition of 5-hydroxytrypta-mine (5HT, 5.0 Amol/L)-induced platelet aggregation at 2 hours. This trend was also observed for 10-,umol/L ADP-induced aggregation. ADP (0.3-0.4 /imol/L)-induced PSC was significantly inhibited at 4 hours (increase in median platelet volume, 6.3%, 1.8-10.7 vs. 1.2%, 0-5.3; p = 0.01). 5HT (0.5 /Lmol/L)-induced PSC at 4 hours was also significantly inhibited (8.1, 5.3-10.6 vs. 3.0, 0-8.2; p = 0.03). A loading dose of clopidogrel (300 mg) inhibits platelet activation in PAD patients, as early as 2 hours. To the authors' knowledge, no other study considered the effect of a loading dose of clopidogrel in PAD.