CYP2C19-Clopidogrel Genetic Testing
Anti-platelet therapy with clopidogrel (Plavix) and aspirin is the standard of care for secondary prevention of myocardial infarction. Despite its widespread use, 4 - 32% of individuals are not responsive to clopidogrel. Through the first genome-wide association study (GWAS) of its kind, we found that the loss of function cytochrome P450 2C19*2 (CYP2C19*2) variant is a major determinant of clopidogrel response. In an independent cohort of patients undergoing percutaneous coronary interventions, we found that patients harboring CYP2C19*2 (~30% of the population) have poorer platelet response to clopidogrel and are at a 2.4-fold higher risk of having an ischemic cardiac event or death. In response to these findings and those of other investigators, the FDA issued a boxed warning on Plavix that it may have reduced effectiveness in people who carry loss of function variants.
Through our NIH funded research study, we have worked with the Translational Genomics Laboratory and physicians at the University of Maryland Medical Center and Baltimore VA Medical Center’s cardiac catheterization laboratories to offer CYP2C19 genetic testing to patients beginning in 2013. Since then, over 580 patients have been enrolled in the study and tested for CYP2C19 genotype.
The University of Maryland, Baltimore is one of seven sites within the Pharmacogenomics Research Network that is offering pharmacogenetic testing to patients in both clinical and research settings.
To advance the science of anti-platelet pharmacogenomics and its clinical translation through CYP2C19 genetic testing for patients undergoing percutaneous coronary interventions.
NHLBI NIH grant U01HL105198
Nanosphere, Inc. (Northbrook, IL)
Alan R. Shuldiner, MD
For General Questions Contact the Clinical Research Team:
PPGM clinical research office 410-706-6140