Genetic Determinants of Response to P2Y12 Inhibitors and Clinical Implications

Abstract

The CYP2C19 enzyme metabolizes clopidogrel, a prodrug, to its active form. Approximately 30% of individuals inherit a loss-of-function (LoF) polymorphism in the CYP2C19 gene, leading to reduced formation of the active clopidogrel metabolite. Reduced clopidogrel effectiveness has been well documented in patients with an LoF allele following an acute coronary syndrome or percutaneous coronary intervention. Prasugrel or ticagrelor is recommended in those with an LoF allele as neither is affected by CYP2C19 genotype. Although data demonstrate improved outcomes with a CYP2C19-guided approach to P2Y₁₂ inhibitor selection, genotyping has not yet been widely adopted in clinical practice.

Keywords: CYP2C19; Clopidogrel; Genotype; Pharmacogenomics; Prasugrel; Ticagrelor.