Genotyping & Plavix Resistance

Clopidogrel is a drug sold under the brand name Plavix that is designed to help prevent stroke and heart attack in high-risk patients. Following a number of studies, the FDA appended an additional warning to the prescription information for Plavix in March of 2010; the FDA found that patients with a specific version of a gene called CYP2C19 would experience less benefit from the drug.

Genotyping

• The process of identifying a patient's genes or what version of a specific gene a patient inherited is called genotyping. Labs use a variety of methods for human genotyping. A technique called polymerase chain reaction (PCR), for instance, enables a technician to amplify or make numerous copies of a specific portion of the genome for analysis. DNA sequencing is another option; while DNA sequencing was once prohibitively expensive, the cost is dropping rapidly. Scientists can also use a probe (a short sequence of DNA that will bind to a matching sequence in the genome) to identify genetic variations at a specific locus (the location of a gene on a chromosome).

Plavix

• Plavix, or clopidogrel, is a kind of drug that is referred to as an antiplatelet in that it helps prevent or inhibit blood clotting, an important precaution in patients at high risk of a stroke. It's a prodrug, meaning that it only becomes active once it's been metabolized by your liver. Until the drug is chemically altered by your liver cells, it won't actually function as intended. The enzymes in your liver that modify the drug belong to a class of proteins called cytochrome P450 enzymes; one of these enzymes is coded by a gene called CYP2C19.

CYP2C19

• There are different variants or alleles of the CYP2C19 gene in the human population. Two studies published in the New England Journal of Medicine in late 2008 found the drug was less effective in patients with certain CYP2C19 alleles; moreover, the studies showed these patients were at higher risk for cardiovascular problems than other patients treated with the drug. Following other studies, the FDA added another warning to the drug's prescription information in March 2010. According to the FDA's safety and labeling information for Plavix, patients who have inherited certain alleles of CYP2C19 are less likely to benefit from taking Plavix; the reduced-function alleles of this gene don't break down the drug properly in the liver, so the drug may not function as intended.

Significance

• The FDA's findings on Plavix and CYP2C19 are a dramatic illustration of the untapped potential of pharmacogenomics, an emerging approach in pharmacology that seeks to tailor treatment to individual patients. Since all patients are genetically different, there may be some drugs that benefit patients with a particular genetic makeup more than they would benefit other patients. Identifying these kinds of genetic variations and incorporating this information into treatment plans and decisions could help improve the standard of care and minimize side effects.

Considerations

• Lab tests can determine which alleles of the CYP2C19 gene you carry; for patients that have inherited reduced-function alleles, there are other drugs available, although these too have their own side effects and limitations. If you're a patient at high risk of stroke or heart attack and are deciding on a treatment plan with your doctor, you may want to discuss your options to find out whether genotyping is necessary and what treatment will work best for you.