Pharmacogenetics of Antiplatelet Therapy

Abstract

Antiplatelet therapy is used in the treatment of patients with acute coronary syndromes, stroke, and those undergoing percutaneous coronary intervention. Clopidogrel is the most widely used antiplatelet P2Y12 inhibitor in clinical practice. Genetic variation in CYP2C19 may influence its enzymatic activity, resulting in individuals who are carriers of loss-of-function CYP2C19 alleles and thus have reduced active clopidogrel metabolites, high on-treatment platelet reactivity, and increased ischemic risk. Prospective studies have examined the utility of CYP2C19 genetic testing to guide antiplatelet therapy, and more recently published meta-analyses suggest that pharmacogenetics represents a key treatment strategy to individualize antiplatelet therapy. Rapid genetic tests, including bedside genotyping platforms that are validated and have high reproducibility, are available to guide selection of P2Y12 inhibitors in clinical practice. The aim of this review is to provide an overview of the background and rationale for the role of a guided antiplatelet approach to enhance patient care.

Keywords: CYP2C19; dual antiplatelet therapy; guided antiplatelet therapy; pharmacogenetics; pharmacogenomics; precision medicine.

Figure 1

A proposed algorithm using CYP2C19 pharmacogenetic testing to individualize oral P2Y12 inhibitor therapy in patients with coronary artery disease on the basis of the meta-analysis results. The overall prevalence of 30% CYP2C19 LOF carriers does not reflect the prevalence of up to 50% observed in Asian populations. Abbreviations: ACS, acute coronary syndrome; CAD, coronary artery disease; CI, confidence interval; LOF, loss-of-function; PCI, percutaneous coronary intervention; RCT, randomized clinical trial. Figure adapted from Reference 110. Illustrations copyright Mayo Clinic.