deCODE Clopidogrel™
Analyzes five SNPs in the CYP2C19 gene that affect response to the anti-platelet drug clopidogrel. This test identifies those who may need adjustment of their clopidogrel dose or who should be put on an alternative medication to prevent recurrent adverse cardiovascular events.
Personalizing therapy
How deCODE Clopidogrel™ can help.
Detecting carriers of reduced function alleles in the CYP2C19 gene identifies those who have decreased bioconversion of clopidogrel to its active metabolite and a decreased anti-platelet response. As a result, they may be at increased risk of recurrent adverse cardiovascular events despite their anti-platelet drug treatment.
The U.S. Food and Drug Administration (FDA) has added a Boxed Warning to the label for clopidogrel, informing health care providers of the availability of the CYP2C19 genetic test for the identification “poor metabolizers”, for whom other anti-platelet medications or alternative dosing strategies should be considered.
deCODE Clopidogrel™ detects five variants within the cytochrome P-450 2C19 gene known to affect the oxidative activation of the anti-platelet agent clopidogrel to its active form.
The variants measured are four SNPs whose loss-of-function alleles have been designated as CYP2C19 *2, *3, *4 and *8, and one SNP designated *17 that shows gain-of-function effect. All five alleles have been associated with change in the efficiency of the hepatic P450 2C19 enzyme to convert the pro-drug clopidogrel to its active metabolite.
Patients with reduced anti-platelet response to clopidogrel may be at increased risk for recurrent cardiovascular events.
The U.S. Food and Drug Administration (FDA) has added a Boxed Warning to the label for clopidogrel, warning about reduced effectiveness in patients who do not effectively convert the drug to its active form. Health care providers are informed of the availability of the CYP2C19 genetic test for the identification “poor metabolizers”, in which case other anti-platelet medications or alternative dosing strategies should be considered.
Pending ethnicity, 1-23% of the population are poor clopidogrel metabolizers, as defined by being homozygous or compound heterozygous (carriers of two different loss-of-function alleles, one on each chromosome) for the CYP2C19 loss-of-function alleles.
Well established pharmacokinetic effect
The reduction in circulating active clopidogrel in carriers of loss-of-function alleles in the CYP2C19 gene is well established and has a strong pharmacokinetic l base, as does the decreased anti-platelet response by platelet aggregation measurements(1-4).
Clinical significance
Defining a patient’s clopidogrel metabolizing status with their CYP2C19 genotypes can help to select the most appropriate platelet inhibitor for the treatment of atherosclerotic diseases.
The increased risk for recurrent cardiovascular events in patients with reduced anti-platelet response has been confirmed by several studies(1,2,4-9,14). In two other studies, the presence of reduced function CYP2C19 alleles was found to have no or limited impact on primary efficacy outcome compared to non-carriers(10,11).
This content was last reviewed on May 12, 2011.