Beneficial effects of clopidogrel combined with aspirin in reducing cerebral emboli in patients undergoing carotid endarterectomy

Background - Postoperative thromboembolic stroke affects 2% to 3% of patients undergoing carotid endarterectomy (CEA) and is preceded by 1 to 2 hours of increasing cerebral embolization. Previous work has demonstrated that high rates of postoperative embolization are associated with increased platelet reactivity to adenosine 5'-diphosphate (ADP). Our hypothesis was that preoperative administration of the platelet ADP antagonist clopidogrel could reduce postoperative embolization. Methods and Results - One hundred CEA patients on routine aspirin therapy (150 mg) were randomized to 75 mg clopidogrel (n = 46) or placebo (n = 54) the night before surgery. Platelet response to ADP was assessed by whole-blood flow cytometry. The number of emboli detected by transcranial Doppler within 3 hours of CEA was independently quantified. Time taken from flow restoration to skin closure was used as an indirect measure of the time to secure hemostasis. In comparison with placebo, clopidogrel produced a small (8.8%) but significant reduction in the platelet response to ADP (P < 0.05) while conferring a 10-fold reduction in the relative risk of those patients having >20 emboli in the postoperative period (odds ratio, 10.23; 95% CI, 1.3 to 83.3; P = 0.01, Fisher's exact test). However, in the clopidogrel-treated patients, the time from flow restoration to skin closure (an indirect marker of hemostasis) was significantly increased (P = 0.04, Fisher's exact test), although there was no increase in bleeding complications or blood transfusions. Conclusions - This is the first study to show that a CEA patient's postoperative thromboembolic potential can be significantly reduced by targeted preoperative antiplatelet therapy without increasing the risk of bleeding complications.