Genotype-Guided Use of P2Y12 Inhibitors: A Review of Current State of the Art

Abstract

The pharmacodynamics of the purinergic receptor type Y, subtype 12 (P2Y12) inhibitors has evolved. Our understanding of the metabolism of P2Y12 inhibitors has revealed polymorphisms that impact drug metabolism and antiplatelet efficacy, leading to genetic testing guided therapy. In addition, assays of platelet function and biochemistry have provided insight into our understanding of the efficacy of “antiplatelet” therapy, identifying patients with high or low platelet reactivity on P2Y12 therapy. Despite the data, the implementation of these testing modalities has not gained mainstream adoption across hospital systems. Given differences in potency between the three clinically available P2Y12 inhibitors, the balance between thrombotic and bleeding complications must be carefully considered, especially for the large proportion of patients at higher risk for bleeding. Here we review the current data for genetic and functional testing, risk assessment strategies, and guidelines for P2Y12 inhibitors guided therapy.

Expression of Variability of the Cyp2c19*2 Gene in Patients With Acute Myocardial Infarction From a South American Hospital and Its Future Relevance in the Interaction Between Genetics and Cardiology

“…Depending on the allele present in the polymorphisms that have been described in previous studies, the enzymatic activity of this cytochrome can be normal, reduced or increased (8)(9)(10)(11). According to the genotype, individuals can be classified into three groups, extensive metabolizers (*1/*1), intermediate (*1/*2 or *1/*3) and poor (*2/*2, *2 /*3, *3/*3) (13).…”

Neutrophil extracellular traps mediate deep vein thrombosis: from mechanism to therapy

“…A previous study investigated the effect of NETs produced in vitro on washed platelets and described that NETs produced in vitro directly induced platelet aggregation and provided a scaffold for platelet aggregation ( 114 ). The platelet surface purinergic receptor type Y, subtype 12 (P2RY 12 ), binds to APD and plays an instrumental role in early DVT formation ( 115 , 116 ). NETs not only provide a scaffold for platelet adhesion and aggregation but may also interact with fibrin to influence thrombus stability ( 117 ).…”