Geentic Study of Clopidogrel Pharmacogenetics
Evaluation of genetic variants that contribute to Clopidogrel pharmacokinetics
Is still used worldwide as an antiplatelet agent in the treatment and prevention of atherothrombotic events?
Inhibits platelet aggregation, affecting platelets irreversibly for the remainder of their lifespan?
Why Clopidogrel pharmacogenetics matter?
According to the FDA, Clopidogrel pharmacogenetics can play an important role in:
Genetic Study of Clopidogrel Pharmacogenetics
Evaluation of the genotypes that affect Clopidogrel metabolism.
Providing an andequate antithrombotic therapy is important to prevent blood clots.
Reducing the adverse drug reactions by precribing the most adequate clopidogrel dose may prevent serious or life-threatening events.
It is recommended for:
Individuals starting Clopidogrel therapy;
Clopidogrel Pharmacogenetics Testing
What is evaluated in this test?
The test evaluates 3 genetic variants in CYP2C19 gene associated with clopidogrel’s pharmacokinetics and pharmacodynamics, whose produce 9 haplotypes related to the level of clopidogrel’s metabolization.
Polymorphisms within CYP2C19 gene can either increase (gain-of-function alleles) or decrease (loss-of-function allels) the catalytic activity of the encoded enzyme, resulting in four possible phenotypes that affect clopidogrel metabolism and consequent platelet inhibition as follows:
Degree of platelet inhibition
Normal platelet inhibition. Normal residual platelet aggregation.
|*1/*17; *17/*17||Ultrarapid metabolizer||
Increased platelet inhibition. Decreased residual platelet
*1/*2; *1/*3; *2/*17
Reduced platelet inhibition
*2/*2; *2/*3; *3/*3
Significantly reduced platelet inhibition
Benefits of Genetic Study of Clopidogrel Pharmacogenetics
Genetic Study or Clopidogrel Pharmacogenetics is a reliable test that distinguishes non-responsive or drug resistant patients.
A sample of blood or saliva is enough to perform the genetic test.
Defines the genetic risk of adverse cardiovascular events and platelet aggregation.
Genetic Study of Clopidogrel Pharmacogenetics defines the Clopidogrel optimal dose therapy and/or recommends for alternative anti-platelet therapy.
Define drug exposure and clinical response variability.
Up-to-date genetic information.
Clopidogrel Administration issues
Being a prodrug, clopidogrel needs hepatic bioactivation into and active form (Clo-AM) in order to inhib platelet aggregation. CYP2C19 is an important hepatic durg-metabolizing enzyme and is responsible for the metabolic activation of clopidogrel. It is well established that clopidogrel`s metabolic activation can be impaired by genetic variants in CYP2C19 gene by concomitant medications that interfere with CYP2C19 action.
The clinical importance of CYP2C19 genotype affecting clopidogrel pharmacokinetics and pharmacodinamics has been extensively studied in the recent years. CYP2C19 genetic polymorfism have been shown to impair the metabolism of this antiplatelet drug. Loss-of-function polymorphisms affect the degree of platelet inhibition by decreasing Clop-Am levels, resulting in an increased risk of recurrence of major adverse cardiovascular events. Conversely, gain-of-function allels are associated with increased risk of bleeding.
Key protein and gene:
CYP2C19–Cytochrome P450, Family 2, Subfamily C, Polypeptide 19
CYP2C19 is a important hepatic drug-metabolizing enzyme and is responsible for the metabolic activation of clopidogrel.
Clopidogrel genetic painel
The Clopidogrel genetic test developed by HeartGenetics includes the evaluation of 3 genetic variants in CYP2C19 gene.
How Genetic variants are selected:
Our research is supported by peer review papers that have been published in the reference journals in the field.
All genetic variants have been validated in reference databases (HGMDP, NCBI-OMIM, NCBI- ClinVar, NCBI-Variation Reporter and Ensembl).
The knowledge in our databases was approved by internationally recognized medical geneticists and cardiologists.
Genetic testing is recommended by several renowned international organizations, such as the Food and Drug Administration (FDA) and the Clinical Pharmacogenetics Implementation Consortium (CPIC)
According to the Food and Drug Administration:
The FDA issued a Boxed Warning about patients who do not effectively metabolize clopidogrel and therefore may not receive the full benefits of the drug. It is recommended the health care professionals consider the use of other antiplatelet medications or alternative dosing strategies for clopidogrel. It was also stated that CYP2C19 genetic testing could be useful to optimize drug therapy
HeartGenetics’ Clopidogrel Pharmacogenetics reports?
The Clopidogrel painel includes genetic variants associated to clopidogrel pharmacokinetics and relative risk of adverse cardiovascular events.
The used technology has a 99% of accuracy.
All evidences are supported by updated scientific knowledge and validated by medical doctors.
All results include supporting information for each genetic variant including scientific references to guide the interpretation of test results.
HeartGenetics reports follow the recommendations from the European Society of Human Genetics
Contact us here for a report example.
 Food and Drug Administration webpage: http://www.fda.gov/
-  JAMA. 2011. 306(24):2704-14. CYP2C19 genotype, clopidogrel metabolism, platelet function, and cardiovascular events: a systematic review and meta-analysis.
-  Mol Biol Rep. 2011. 38(3):1697-702. Cytochrome P450 2C19 polymorphism is associated with poor clinical outcomes in coronary artery disease patients treated with clopidogrel.
-  Circulation. 2010. 121(4):512-8. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement.
-  J Thromb Haemost. 2012. 10(2):199-206. The gain-of-function variant allele CYP2C19*17: a double-edged sword between thrombosis and bleeding in clopidogrel-treated patients.
-  JAMA. 2010. 304(16):1821-30. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis.
-  Clin Pharmacol Ther. 2013. 94(3):317-23. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update.
-  Clin Pharmacol Ther. 2012. 92(4):414-7. Pharmacogenomics knowledge for personalized medicine.