title: Pharmacogenomics of anti-platelet therapy: how much evidence is enough for clinical implementation?
abstract: Pharmacogenomics, the study of the genomics of drug response and adverse effects, holds great promise for more effective individualized (personalized) medicine. Recent evidence supports a role of loss-of-function (LOF) variants in the cytochrome P450 enzyme CYP2C19 as a determinant of clopidogrel response. Patients given clopidogrel after percutaneous coronary intervention who carry LOF variants do not metabolize clopidogrel, a prodrug, into its active form resulting in decreased inhibition of platelet function and a higher likelihood of recurrent cardiovascular events. Despite a large body of evidence supporting clinical utility, adoption of anti-platelet pharmacogenetics into clinical practice has been slow. In this review, we summarize the pharmacokinetic, pharmacodynamic and clinical evidence, identify gaps in knowledge and other barriers that appear to be slowing adoption, and describe CYP2C19 pharmacogenetics implementation projects currently underway. Only when we surmount these barriers will clinicians be able to use pharmacogenetic information in conjunction with the history, physical examination and other medical tests and information to choose the most efficacious anti-platelet therapy for each individual patient.
authors.affiliation: Program in Personalized and Genomic Medicine, and the Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Christina G
authors.initials: CG
authors.lastname: Perry
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D019317:Evidence-Based Medicine; D005838:Genotype; D006801:Humans; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010597:Pharmacogenetics; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine