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.


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.
Department of Surgery, University of Leicester, Leicester, UK.
David A
DA
Payne
Chris I
CI
Jones
Paul D
PD
Hayes
Matthew M
MM
Thompson
Nicholas J
NJ
London
Peter R
PR
Bell
Alison H
AH
Goodall
A Ross
AR
Naylor
D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D000077144:Clopidogrel; D018450:Disease Progression; D004359:Drug Therapy, Combination; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D020766:Intracranial Embolism / Q000000981:diagnostic imaging / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000000981:diagnostic imaging / Q000517:prevention & control*; D011184:Postoperative Period; D011292:Premedication; D012306:Risk; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial; D014945:Wound Healing / Q000187:drug effects
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin