Date: 16 Mar 2008

Optimal management of platelet function after coronary stenting

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Opinion statement

Coronary stenting elicits vessel wall damage, and subsequent activation of platelets is implicated as a major component of complications such as acute, subacute, and late stent thrombosis. As such, dual antiplatelet therapy using aspirin and clopidogrel has become a routine adjunct to coronary stenting. Use of aspirin and clopidogrel with or without glycoprotein IIb/IIIa inhibitors after coronary stenting reduces the complication rate and improves long-term outcomes. Dual antiplatelet therapy using aspirin and clopidogrel is recommended for at least 4 weeks with bare metal stents, and for 3 to 6 months with drug-eluting stents for prevention of major adverse cardiac events. After coronary stenting, 1 year of dual antiplatelet therapy is recommended for prevention of future cardiac events. However, despite the use of antiplatelet agents, stent thrombosis occurs in approximately 1% of patients, with an increased likelihood of occurrence in high-risk patients or a lesion subset of patients. Although the incidence of stent thrombosis is low, stent thrombosis usually presents as acute coronary syndrome and the mortality rate is up to 45%. Thus, considering the widespread use of stents, a considerable number of people are inadequately protected from thrombotic events despite current standard antiplatelet therapy using aspirin and clopidogrel. A concern with clopidogrel is the loading time and loading dose required to achieve and maintain optimal inhibition of platelet aggregation. The current recommendation for ensuring maximum antiplatelet activity is administration of a 300-mg loading dose of clopidogrel initiated at least 6 hours prior to percutaneous coronary intervention (PCI), and ideally the day before. If this is not possible, a loading dose of 600 mg of clopidogrel should be administered at least 2 hours before PCI. Recently, new combinations of antiplatelet agents (ie, triple therapy using aspirin, clopidogrel, and cilostazol) and new drugs with potent antiplatelet effects (ie, Prasugrel [currently being developed by Sankyo Pharmaceuticals and Ube Pharmaceuticals in Japan and by Eli Lilly and Co. (Indianapolis, IN) in the United States], Cangrelor [currently being developed by AstraZeneca Pharmaceuticals, Wilmington, DE], and AZD6140) have been evaluated in clinical trials; such treatments may help reduce the number of cardiac events after coronary stenting.