Drug Insight: clopidogrel nonresponsiveness

Platelet reactivity to agonists and subsequent activation are important factors that affect the development of atherothrombosis and resultant ischemic events. Pharmacologic intervention with clopidogrel and aspirin during acute coronary syndromes and percutaneous coronary intervention is considered the gold standard for attenuating platelet activation and aggregation. Despite significant benefits reported with dual antiplatelet treatment in major clinical trials, the occurrence of adverse ischemic events, including stent thrombosis, remains a serious clinical problem. Nonresponsiveness, also called resistance, to current clopidogrel regimens might play a part in the occurrence of ischemic events. Various mechanisms have been implicated in nonresponsiveness to clopidogrel, including variability in intestinal absorption and hepatic conversion to the active metabolite, drug–drug interactions and receptor polymorphisms. Increased loading and maintenance doses and the use of new and more-potent P2Y12-receptor blockers might overcome the phenomenon of clopidogrel nonresponsiveness. The aim of this article is to provide a comprehensive and current review of clopidogrel response variability and nonresponsiveness.