At a Glance

Why Get Tested?

To help evaluate your likely response to the antiplatelet drug clopidogrel by detecting variations in the gene (CYP2C19) that codes for one of the enzymes that metabolizes the drug; clopidogrel is prescribed for people who are at risk of a heart attack or stroke to help prevent harmful blood clots from forming.

When To Get Tested?

A health care practitioner might order this test prior to prescribing clopidogrel for you or during the initial treatment phase and sometimes when you are taking clopidogrel and are not responding as expected.

Sample Required?

A blood sample drawn from a vein, a swab rubbed on the inside of your cheek, or you spit saliva in a clean container.

Test Preparation Needed?

None

What is being tested?

This test helps determine if you may be less responsive to the drug clopidogrel because of your genetic makeup. This test detects genetic variation in the gene CYP2C19. A health care practitioner may sometimes order this test to determine whether clopidogrel will be effective for you or if another drug for treatment may be required.

Clopidogrel is a drug that is part of a group of medications called antiplatelet drugs and is used to prevent strokes and heart attacks in people who are at increased risk for these serious cardiovascular events. The drug works by helping to prevent harmful blood clots from forming by preventing platelets from clumping together (aggregating).

Normally, when an injury occurs to blood vessels, platelets in the blood stick to the site of injury and clump together to start the formation of a blood clot and help stop the bleeding. In people at increased risk for heart attack or stroke, this process can occur inappropriately, so they may be treated with drugs that prevent platelet aggregation.

Clopidogrel is given in an inactive form (i.e., prodrug) and must be changed (metabolized) by the body to an active form before it can be effective. Some people who have some genetic variations in the gene CYP2C19 do not metabolize clopidogrel to its active form as well as people who do not have these genetic variations in CYP2C19. Therefore, individuals with CYP2C19 genetic variations who are taking clopidogrel may not receive adequate benefit from the drug and may be at risk of having a heart attack or stroke. This test identifies people who have one or more CYP2C19 variants.

You inherit one copy of each of your genes from your mother and one copy from your father. Thus, the CYP2C19 gene is present in the body as two inherited gene copies (alleles). You could have both copies of a gene without any variants (wild-type, normal); one copy without variants and one copy with a variant (heterozygous); both copies with the same variant (homozygous); or both copies with different variants (compound heterozygous). The combination of the CYP2C19 gene copies that you have can determine how effectively clopidogrel is changed to its active form in your body and its overall effect.

Clopidogrel responsiveness (or clopidogrel genotype) testing determines whether CYP2C19 gene variants are present. Careful interpretation of the results can help the healthcare provider decide the appropriate antiplatelet treatment for you.

Common Questions

How is the test used?

This test is used to determine your potential responsiveness to clopidogrel, an antiplatelet medication, before you start taking the drug or during the initial treatment phase.

Clopidogrel genotype testing is used to detect variation in the CYP2C19 gene that codes for one of the enzymes responsible for metabolizing clopidogrel into its active form. Variations in CYP2C19 are most often associated with reduced enzyme activity and decreased metabolism of clopidogrel, leading to a low level of active drug and potentially ineffective treatment for risk of blood clots. Testing for variants of the CYP2C19 gene is done to help tailor treatment for an individual (known as pharmacogenetic testing). If you have certain genetic variations, you may require an alternative therapy to treat your condition more effectively.

Clopidogrel-related genetic testing is not widely used at this time. Although studies have shown that CYP2C19 variation contributes to a person’s responsiveness to clopidogrel, there is no agreement yet among experts on the need for the testing. Part of the reason is that genetic variants of CYP2C19 explain only some of the treatment response variability among people.

When is it ordered?

Clopidogrel resistance testing is primarily ordered prior to having you take clopidogrel for the first time or during the initial treatment phase but may also be ordered when you are being treated with the drug and have experienced either excessive blood clotting or bleeding.

Not everyone who is prescribed clopidogrel will have this test done. At present, there is no consensus on the usefulness of this test and it is not yet widely accepted.

What does the test result mean?

Results of genetic testing require careful interpretation. Typically, your lab report will include an explanation from a healthcare practitioner with expertise in this area. A number of factors are taken into account when determining whether clopidogrel is an appropriate treatment for you.

In general, if you have one or two variant copies of the gene, then you may have an altered response to clopidogrel. The degree of responsiveness depends upon the variation(s) present and upon your body. You may be a normal, poor, intermediate, extensive, or ultra-rapid metabolizer of the drug.

Not every laboratory will test for every gene variant. Laboratories most commonly look for the CYP2C19 variant alleles *2 and *3. A less common gene variant may be present that is not detected by the test. You may also have decreased drug metabolism due to another factor. CYP2C19 gene variation is only one factor in your response to clopidogrel.

Is there anything else I should know?

To increase awareness of the influence of the CYP2C19 gene variations and the availability of testing, the U.S. Food and Drug Administration (FDA) has promoted changes to the Plavix® (clopidogrel) label to inform consumers that genetic factors may affect how well the drug works for them.

The enzyme CYP2C19, coded for by the CYP2C19 gene, metabolizes a wide variety of drugs in addition to clopidogrel. Thus, if you are taking clopidogrel plus one or more additional medications metabolized by CYP2C19, then you may have altered metabolism of clopidogrel and the other drugs. One of the prominent examples of drugs that are metabolized by CYP2C19 is omeprazole that is taken to control stomach acid production. Others include diazepam, anti-seizure medications, and antidepressants.

Testing to predict how someone will respond to a drug is a form of personalized medicine known as pharmacogenomics. Research is ongoing in this field of study in an effort to treat individuals’ conditions effectively, yet avoid side effects.

Is this test different than a platelet function test?

Yes. This test is a genetic test that determines which form of the CYP2C19 gene you have, which may help predict how you will respond to clopidogrel.

Can platelet function assays be used to assess clopidogrel response?

There are several platelet function assays that have been used for detecting nonresponse (termed “clopidogrel resistance”), such as platelet aggregometry with ADP, with collagen epinephrine; however, their clinical utility has not been widely accepted due to poor agreement between the assays.

Should everyone be tested for CYP2C19 gene variations?

Testing is not recommended to screen the general population. It is currently only indicated for those taking a drug that may be influenced by the activity of the CYP2C19-related enzymes. In some cases, a health care practitioner may recommend that family members of a poor metabolizer consider testing so that this information is on record.

Can clopidogrel resistance testing be done in my healthcare provider's office?

No, it requires specialized equipment to perform and expertise to interpret. It is not offered by every laboratory and may need to be sent to a laboratory outside of your hospital (reference laboratory).

Should I tell my other health care providers about my CYP2C19 test results?

Yes, this would be good information for them to have, regardless of whether you are currently taking clopidogrel. CYP2C19 is also associated with response to many other drugs.

Should I tell my healthcare providers that I am taking clopidogrel?

Yes, it is crucial for you to tell all of your health care providers and your dentist that you are taking clopidogrel, aspirin, or another antiplatelet agent. They will need to incorporate this information into any other treatments or procedures.

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