Monitoring Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention

Abstract

Dual antiplatelet therapy with aspirin and thienopyridines is the cornerstone in the treatment of patients with acute coronary syndrome (ACS) and in those undergoing PCI with stent-implantation.However, the magnitude of on-treatment platelet reactivity is not uniform among individuals, due to a multifactorial origin including clinical, pharmacologic and genetic factors. Clopidogrel is a prodrug that requires conversion by hepatic P450 isoenzymes to its active metabolite. Most of the clopidogrel (85%) is hydrolyzed by carboxylase to an inactive carboxylic acid metabolite, whereas the remaining 15% is transformed rapidly into its active metabolite that is able to exert its antiplatelet response by irreversibly inhibiting the binding of adenosinediphosphate (ADP) to the P2Y12 receptor. Recently, paraoxonase-1 (PON1) was identified as the crucial enzyme in clopidogrel bioactivation. Consistent findings across multiple investigations support the association between a lower degree of platelet inhibition, i.e. a high on-treatment platelet reactivity (HPR), and an increased risk for the occurrence of thrombo-ischemic events (Table 1).9-14,14,15,15-27 Multiple factors have been associated with high on-treatment platelet reactivity, among which genetic polymorphisms of cytochrome P450 and of the P2Y12 receptor as well as and drug-drug interactions. Consequently, the monitoring of the magnitude of platelet reactivity has gained widespread attention