Responsiveness to P2Y12 receptor inhibitors

Abstract

Purpose of review: This review is aimed at describing the variability in response to P2Y12 inhibitor agents, and to focus on the main tests currently available to assess the responsiveness.

Recent findings: There is high interindividual response variability to clopidogrel. Some patients do not respond to the drug; this condition can be due to patient-related factors (poor compliance, genetic factors, cardiovascular risk profile) or to drug-related factors (reduced bioavailability or absorption, drug-drug interactions). In particular, mutations of the gene encoding for cytochrome CYP2C19, responsible for clopidogrel metabolism, are associated with an increased risk of cardiovascular events. Many tools for assessing platelet function are now available, but an appropriate test able to correlate platelet function to patient clinical outcome is still far from being recognized. There is also no standardized method to address their role in clinical practice. In addition, the safety and efficacy of alternative treatments for patients with 'clopidogrel resistance' has not been demonstrated yet. The recent findings from the Gauging Responsiveness with a VerifyNow Assay-Impact on Thrombosis and Safety (GRAVITAS) study showed that increasing the dose of clopidogrel in patients who are resistant does not decrease the incidence of cardiovascular events. Therefore, until the results of large-scale trials of personalized antiplatelet therapy are available, the routine use of platelet function measurements in the care of patients with cardiovascular disease cannot be recommended.

Summary: Clopidogrel resistance is associated with higher incidence of cardiovascular events. Despite several available tools to test clopidogrel responsiveness, there is no uniform definition of 'non-responder' patients. The reduction of platelet reactivity in non-responder patients is not associated with reduced cardiovascular events. Current evidence suggests that higher antiplatelet regimens provide clinical benefits to the patient's risk profile rather than his/her 'platelet profile'.