The Evidence Base for Platelet Function Testing in Patients Undergoing Percutaneous Coronary Intervention

Abstract

Clopidogrel therapy significantly reduces cardiovascular events in patients presenting with acute coronary syndrome (ACS)1,2 and in patients undergoing percutaneous coronary intervention (PCI),3 yet cardiovascular events, including stent thrombosis, continue to occur after PCI despite the ischemic benefit conferred by clopidogrel. Minimizing the incidence of stent thrombosis is a central goal for stent manufacturers, pharmaceutical companies, regulatory bodies, and practicing interventional cardiologists, and professional societies have formally recommended prolonged thienopyridine therapy after drug-eluting stent implantation in the absence of randomized controlled clinical trials.4 A growing body of data supports the contention that the level of platelet reactivity on clopidogrel therapy (“on-treatment” platelet reactivity) is an independent risk factor for ischemic and thrombotic events post-PCI and that the intensification of platelet inhibition may improve outcomes in at-risk patients. The introduction of point-of-care and clinical laboratory-based platelet function assays has made it feasible to consider the routine evaluation of on-treatment platelet reactivity in the patient undergoing PCI.5,6 The current data set provides clinicians with a strong scientific rationale for the use of platelet function assays in daily practice. Response by Kalyanasundaram and Berger on p 283 Clopidogrel is a prodrug that requires biotransformation into an active metabolite to exert its inhibitory effect on platelet aggregation. Approximately 85% of absorbed clopidogrel is hydrolyzed by esterases in the gut into an inactive form, and the remainder is converted into an active metabolite by the hepatic cytochrome P450 (CYP) system through a 2-step oxidative process.7 The active metabolite irreversibly binds and antagonizes the P2Y12 ADP receptor for the life of the platelet. The platelet inhibitory response to clopidogrel varies substantially among patients according to ex vivo measurements,8 with many patients having persistently high platelet reactivity despite clopidogrel treatment. Genetic polymorphisms that affect the catalytic activity …