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.
Defining a patient’s Clopidogrel metabolizing status by the CYP2C19 genotypes may be important when selecting the most appropriate platelet inhibitor for the treatment of atherosclerotic diseases.
The FDA Boxed Warning targets the “poor metabolizer” group only, for which other anti-platelet medication or alternative dosing strategies should be considered.
Although a higher dose regimen in poor metabolizers increases anti-platelet response and the FDA advises healthcare professionals to consider alternative dosing strategies, an appropriate dose regimen for poor metabolizers has not been established by clinical studies.
The deCODE Clopidogrel™ test defines five different metabolizing status categories according to patients’ genotype results:
| Genotype Result | Genotype Possibilities | Metabolizing status |
|---|---|---|
| One or two gain-of-function alleles *17 present (no loss-of-function) | *1/*17 or *17/*17 | Ultra metabolizer# |
| None of the altering function alleles present | *1/*1 | Extensive metabolizer |
| One of the decrease-of-function alleles present (*2, *3, *4 or *8) and no gain-of-function allele *17 | *1/*2 or *1/*3 or *1/*4 or *1/*8 | Intermediate metabolizer |
| Two or more decrease-of-function alleles present (*2, *3, *4 or *8) and no gain-of-function allele *17 | *2/*2 or *3/*3 or *4/*4 or *8/*8 or *2/*3 or *2/*4 or *2/*8 or *3/*4 or *3/*8 or *4/*8 | Poor metabolizer |
| Both gain-of-function allele *17 and loss-of-function allele *2, *3, *4, or *8 present | *2/*17 or *3/*17 or *4/*17 or *8/*17 | Unknown metabolizing status## |
# In the outcome study of Pare et al. there was a more pronounced reduction in cardiovascular events in the clopidogrel treated group of gain-of-function allele carriers (irrespective of the presence of a loss-of-function allele) than in non-carriers, as compared to placebo. In figure one of Pare’s paper it can be seen that the rate of cardiovascular events was the lowest in the clopidogrel treated unknown group, even lower than for the ultra metabolizers(10).
## Whereas at least one study has found ultrametabolizers be of increased risk of bleeding(13) Pare et al found no difference in their study(10).
According to the FDA “boxed warning”, modification of clopidogrel dosing or an alternative anti-platelet medication should, if warranted, be considered only for poor metabolizers.
For further information on the significance of FDA’s “Boxed Warning” and the use of CYP2C19 genotype information in patient care, please refer to the American College of Cardiology and the American Heart Association Clopidogrel Clinical Alert from June 2010(15) http://content.onlinejacc.org/cgi/content/full/56/4/321.
Alleles other than those described above, including rare alleles, are not detected by the deCODE Clopidogrel™ test. The metabolism of clopidogrel may also be influenced by race, ethnicity, diet, and/or other medications. The results must be interpreted in the context of other test results and clinical findings. The test results do not rule out the possibility of variant alleles in other drug metabolism pathways that may impact drug efficacy and/or toxicity.
Other common drugs metabolized by the 2C19 pathway and which can thereby interfere with the metabolizing of clopidogrel include proton pump inhibitors (omeprazole), anticonvulsants (phenytoin and diazepam), and tricyclic antidepressants (amitriptyline and nortriptyline).
This content was last reviewed on May 12, 2011.