Intimal
hyperplasia results in significant morbidity and mortality following vascular intervention. Both platelets and elevated
homocysteine have been implicated in the development of intimal
hyperplasia. We previously demonstrated that a locally applied
antiplatelet agent decreases the development of intimal
hyperplasia. We were therefore interested in a systemic
antiplatelet agent,
clopidogrel. We hypothesized that
clopidogrel would decrease platelet aggregation and activity and intimal
hyperplasia. Male Sprague-Dawley rats underwent
carotid endarterectomy (CEA) and treatment with either placebo or varying regimens of
clopidogrel, including chronic, pre-CEA bolus, chronic plus pre-CEA bolus, and chronic plus post-CEA bolus; a
homocystine diet was used to elevate both plasma
homocysteine and the degree of intimal
hyperplasia. Platelet aggregation, platelet activity, and intimal
hyperplasia were then assessed. Platelet aggregation was not decreased with chronic
clopidogrel; however, it was decreased with pre-CEA bolus
clopidogrel. Similarly, platelet activity was not inhibited by chronic
clopidogrel but was inhibited by pre-CEA and chronic plus pre-CEA bolus
clopidogrel. Neither chronic, pre-CEA bolus, chronic plus pre-CEA bolus, nor chronic plus post-CEA bolus
clopidogrel resulted in a decrease in intimal
hyperplasia. Although pre-CEA bolus
clopidogrel resulted in a decrease in both platelet aggregation and activity, it was unable to decrease the development of intimal
hyperplasia at any dose. Additional factors must therefore contribute to the pathologic development of intimal
hyperplasia.