This drug gene interaction (DGI) pertains to the interaction between the cytochrome P450 2C19 (CYP2C19) gene and clopidogrel. Clopidogrel (brand name Plavix®) is used to prevent heart attack and stroke in persons who have recently had a heart attack, stroke, or blood circulation disease (peripheral vascular disease). Clopidogrel works by preventing specific blood cells called platelets from sticking together and forming harmful clots, thus clopidogrel is an ‘anti-platelet drug’ and helps keep blood flowing smoothly in the body. It is also used with aspirin to treat new or worsening chest pain and to prevent blood clots after certain procedures such as a cardiac stent.
Extensive literature and FDA warning labels indicate patients with genetically reduced CYP2C19 function demonstrate lower systemic exposure to the active metabolite of clopidogrel, diminished anti-platelet responses, and generally exhibit higher cardiovascular event rates following a coronary stent procedure than do patients with normal CYP2C19 function.
Information presented on this page is based on evidence provided by the Clinical Pharmacogenomics Implementation Consortium (CPIC®). CPIC provides peer-reviewed, updated, evidence-based, and freely accessible guidelines for implementing pharmacogenomic results into actionable prescribing decisions for providers. CPIC guidelines include standardized terminology and a systematic grading of evidence and clinical recommendations published in a leading journal (Clinical Pharmacology and Therapeutics).
The CYP2C19 (sounds like “sip-2-see-19”) gene encodes the CYP2C19 enzyme, which is a member of the cytochrome P450 enzyme family. There are different CYP2C19 gene versions, or variants, and each has a different effect on how well clopidogrel is metabolized in the body. Some variants result in a non-functioning or low-functioning CYP2C19 protein while other variants result in a normal-functioning CYP2C19 protein. Some variants can lead to an increase in CYP2C19 protein function. Different ‘metabolizer statuses’ are assigned to patients depending on their genetic information. See chart below for a description of each metabolizer status and any implications for treatment.
ONE increased function allele AND ONE no-function allele
Patient’s genetic information is reported as a diplotype and this corresponds to a phenotype (i.e. metabolizer status). To see an interpretation table assigning metabolizer status by genetic variant, click here to visit CPIC and scroll down to click and download “CYP2C19 diplotype-phenotype table”.
Clopidogrel is a medicine used to manage several different conditions and your genes can affect how well the drug works. CPIC updates guidelines on how to best use these genetic results to support patient care and has published its current recommendations here.
Genotyping for CYP2C19 was performed within a certified DNA laboratory at Vanderbilt University Medical Center that is in full compliance with all guidelines established by the government as regulated by the Centers for Medicare & Medicaid Services under the Clinical Laboratory Improvement Act of 1988. This validated clinical laboratory developed test is carried out with strict adherence to protocols outlined by the College of American Pathology. The performance of the assay is closely monitored and the accuracy of the results is determined to be > 99%.
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C19 Genotype and Clopidogrel Therapy
This link will take you to the main page on the CPIC website relating to CYP2C19 and clopidogrel. On the site, you will find links to the main guideline publication and all supplementary information including a table that reports variant frequencies across different races/ethnic groups, a table that defines genetic variants, and a table that provides a phenotype interpretation (i.e. metabolizer status). Additionally, examples of point of care clinical decision support can be found at the bottom of the page.
Please note that additional drugs may have CYP2C19 interactions. For more information on drug-gene interactions, please use the search feature on the CPIC website.
Additionally, a comprehensive evidence summary has been provided by the VUMC Informatics Center Knowledge Management (KM) Team. This information was developed by the KM team in response to questions from VUMC clinicians and researchers about topics related to genetics and health. The syntheses provided are copyrighted and should not be re-used without permission.