Therapeutic Benefit of Low-Dose Clopidogrel in Patients Undergoing Carotid Surgery is Linked to Variability in the Platelet Adenosine Diphosphate Response and Patients’ Weight

Background and Purpose— We have previously shown that a single 75-mg tablet of clopidogrel, taken before carotid endarterectomy, significantly reduces postoperative embolization, a marker of thromboembolic stroke. This study explores the antiplatelet effect of this submaximal dose. Methods— Fifty-six patients on long-term aspirin (150 mg) were randomized to 75 mg clopidogrel or placebo before carotid endarterectomy. Blood samples were taken pre- and postdrug administration and at the end of surgery to measure platelet activation and adenosine diphosphate (ADP) response by flow cytometry and aggregometry. Results— Surgery produced a significant rise in platelet activation in vivo as evidenced by a rise in the percentage of monocyte–platelet aggregates in patients given placebo, but this was not seen in patients receiving clopidogrel. Before surgery, clopidogrel produced a significant reduction in the platelet response to ADP; for example, with 10−6M ADP, 77.32±2.3% bound fibrinogen in placebo group compare...