Clopidogrel resistance: implications for coronary stenting.
Clopidogrel, in combination wih aspirin, is currently the drug of choice to prevent thrombosis after coronary stent implantation. Currently, clopidogrel is administered to the vast majority of patients without any assessment of platelet inhibition. Response variability and resistance, however, definitely occur to clopidogrel treatment. Preliminary data support the hypothesis that patients with reactive or clopidogrel nonresponsive platelets are at risk for thrombotic events. However, the magnitude of the clinical effect remains unknown and relationship between nonresponsiveness and risk of clinical events is under-investigated. Several important questions that must be answered are: A) What is the relation of clopidogrel resistance and high platelet reactivity to the occurrence of stent thrombosis, recurrent myocardial infarction, stroke and death?; B) Is there a threshold of platelet reactivity that correlates with the onset of thrombotic risk?; and C) What is the cost of administering clopidogrel to non-responsive patients? Finally, our understanding of the clinical relevance of drug resistance and high platelet reactivity should be facilitated by the use of validated point-of-service devices. The mechanisms of the response variability to clopidogrel remain incompletely defined. The contribution of intra- and extracellular pathways are under investigation.
Gurbel
Paul A
PA
Sinai Center for Thrombosis Research, Baltimore, Maryland 21215, USA. Pgurbel@lifebridgehealth.org
Lau
Wei C
WC
Bliden
Kevin P
KP
Tantry
Udaya S
US
D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000601:surgery*; D004351:Drug Resistance; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D018048:Receptors, Purinergic P2 / Q000187:drug effects; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D000077144:Clopidogrel; D013988:Ticlopidine