Overcoming Obstacles in Pharmacogenomic Strategies for Antiplatelet Drugs: Are we Rapid Enough?

Abstract

Advances in various fields of medicine have potentiated the need for pharmacogenomic treatment strategies. Screening of HLA-B*5701 to decrease hypersensitivity response to abacavir [1] and the potential use of a GLCCI1 functional polymorphism to predict glucocorticoid response in asthma patients [2] are two of many examples where identification of genetic variants may potentially optimize pharmacotherapy. In cardiology, the impaired response to the antiplatelet drug clopidogrel [3] among CYP2C19 loss-of-function allele carriers has highlighted the imminent need for personalized strategies. While there is universal enthusiasm for the concept of pharmacogenomics, its implementation in the clinical setting faces many ongoing challenges. Recently, we published the RAPID GENE study [4], a clinical trial that validated the first bedside point-of-care genetic test in clinical medicine. In doing so, we had overcome a major impediment associated with executing pharmaco genomic strategies in the clinical setting. However, major obstacles exist that currently prevent widespread implementation of these findings into practice. As such, developments in pharmacogenomics for antiplatelet drugs may act as an ideal case study to underline the challenges that confront the greater field of clinical pharmacogenomics. Clopidogrel, a prodrug requiring biotransformation by the CYP450 system, is integral in the prevention of major adverse cardiovascular events (MACE) after implantation of coronary stents in patients with coronary artery disease. In the optimal setting, only 15% of the drug is transformed into the active metabolite that exerts an inhibitory effect on the platelet P2Y 12 receptor [5]. Despite treatment with clopidogrel, patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI)