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.
The American Heart Association estimated for the year 2009, that despite availability of dual platelet inhibitor treatment (clopidogrel plus aspirin) for unstable coronary syndromes, 470.000 recurrent cardiac events could be expected.
Given that the loss of CYP2C19 function alleles are so common, and the number of possibly preventable cardiovascular events so large, optimizing of anti-platelet therapy on basis of CYP2C19 loss-of-function genetic testing has significant potential for preventing CV events.
Loss-of-function alleles in the CYP2C19 gene are common in the general population, occurring in about 30% of people of European descent, 35% of African-Americans, and 60% of people of Asian descent. Homozygosity and compound heterozygosity (the presence of two different loss-of-function alleles, one on each chromosomes) leading to the poor metiabolizer phenotype occur in 1-6% of those of European ancestry, 1-7.5% of African-Americans, and 12-23% of people of Asian anscestry(12). The majority of loss-of-function alleles are accounted for by the *2 and *3 alleles, which are carried by 85 % of European-descent poor metabolizers and 99% of Asian-descent poor metabolizers.
Other alleles associated with absent or reduced metabolism are less frequent and include but are not limited to: CYP2C19 *4, *5, *6, *7, *8 and *10. Of these, *2, *3, *4, and *8 are included in the deCODE Clopidogrel™ test, as is *17, the gain-of-function allele resulting in what has been defined (in the absence of one of the loss-of-function alleles) as an ultrametabolizing phenotype.
Recent studies have investigated the association between CYP2C19 genoytpes and clinical outcomes in patients. Several studies(1,2,4-9,14) have shown 1.5- to 4-fold more frequent adverse cardiovascular event rates in CYP2C19 loss-of-function allele carriers and poor metabolizers than in non-carriers. Two other studies found that the presence of reduced function CYP2C19 alleles made no or limited difference in primary efficacy outcome compared to that of non-carriers(10,11).
This content was last reviewed on May 12, 2011.