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(Stroke. 2007;38:2464.)
© 2007 American Heart Association, Inc.

Original Contributions

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

David A. Payne, FRCS(Ed); Chris I. Jones, MSc; Paul D. Hayes, MD; A. Ross Naylor, MD Alison H. Goodall, PhD

From the Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.

Correspondence to Professor Alison H. Goodall, Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Leicester, LE3 9QP, UK. E-mail ahg5{at}le.ac.uk

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 compared with 67.16±3.1% after clopidogrel (P=0.01). This was accentuated after surgery when the percentage of platelets binding fibrinogen in response to ADP was 76.53±2.2% in patients given placebo and 62.84±3.3% in the clopidogrel group (P=0.002). Similar differences were seen over a range of ADP concentrations and by aggregometry. Platelet responsiveness before treatment was highly variable and was positively correlated with the inhibitory effect of clopidogrel; patients with the highest baseline response to ADP showed the greatest response to clopidogrel. A negative correlation was seen between the effect of clopidogrel and patients’ weight (r=0.57; P=0.002).

Conclusions— These results explain how a single 75-mg dose of clopidogrel produces a significant clinical impact on embolization.

Key Words: carotid endarterectomy • clopidogrel • platelets