Genotyping genetic variants of CYP2C19 for precision antiplatelet dosing: state of the art and future perspectives

Abstract

Introduction: Clopidogrel is the only antiplatelet agent whose activity is significantly affected by CYP2C19 polymorphism.

Areas covered: This review has summarized the available evidence on the clinically significant association between CYP2C19 polymorphism and clopidogrel-based therapy; reviewed the current recommendations for clinical use of CYP2C19 genotype test results in patients on clopidogrel treatment; and discussed possible pitfalls of routine application, and future perspectives of antiplatelets pharmacogenetics.

Expert opinion: The available body of evidence, reflected in several meta-analyses and high-quality clinical practice guidelines, shows that the presence of CYP2C19 LOF alleles, especially CYP2C19*2, correlates with impaired activation of clopidogrel and variable platelet inhibition, followed by minimal or no antiplatelet effect, and higher risk of treatment failure. In combination with other known risk factors, CYP2C19 genetic testing could be very valuable in predicting low clopidogrel efficacy. At the same time, it could be very successful in selecting patients who will most probably benefit from the clopidogrel-based therapy, thus decreasing the pool of those who might need more expensive and otherwise riskier antiplatelet alternatives.

Keywords: Antiplatelets; CYP2C19; clopidogrel; genotyping; precision dosing.