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 metabolises 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.
Clopidogrel (CYP2C19 Genotyping)
A healthcare professional may request 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.
A blood sample drawn from a vein in your arm
This test helps determine if a person may be less responsive to the drug clopidogrel because of his or her genetic makeup. This test detects genetic variation in the gene CYP2C19. A healthcare professional may sometimes request this test to determine whether clopidogrel will be effective for the person tested 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 (metabolised) 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 metabolise 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.
Each person receives one copy of each of their genes from their mother and one copy of each of their genes from their father. Thus, the CYP2C19 gene is present in the body as two inherited gene copies (alleles). Any person could have both copies of a gene without any variants (wild-type); one copy without variants and one copy with a variant (heterozygous); both copies with the same variant (homozygous); and both copies with different variants (compound heterozygous). The combination of the CYP2C19 gene copies that a person has can determine how effectively clopidogrel is changed to its active form in the 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 the person tested.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
How is it used?
This test is used to determine an individual's potential responsiveness to clopidogrel, an antiplatelet medication, before a person starts taking the drug or during the initial treatment phase. Clopidogrel is a drug that is prescribed 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).
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. Variation in CYP2C19 is 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). Those with certain genetic variations may require an alternative therapy that would treat their 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 a small proportion of the treatment response variability among people.
When is it requested?
Clopidogrel resistance testing is primarily requested prior to a person taking clopidogrel for the first time or during the initial treatment phase but may also be requested when a person who is being treated with the drug has 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, the lab report will include an explanation from a healthcare professional with expertise in this area. A number of factors are taken into account when determining whether clopidogrel is an appropriate treatment for an individual.
In general, if a person has one or two variant copies of the gene, then that person may have an altered response to clopidogrel. The degree of responsiveness depends upon the variation(s) present and upon the person. An individual may be a normal, poor, intermediate, extensive, or ultra-rapid metaboliser of the drug.
Not every laboratory will test for every gene variant. A less common gene variant may be present that is not detected by the test. A person may also have decreased drug metabolism due to another factor. CYP2C19 gene variation only accounts for a portion of a person's response to clopidogrel.
Is there anything else I should know?
The enzyme CYP2C19, coded for by the CYP2C19 gene, metabolises a wide variety of drugs in addition to clopidogrel. Thus, if a person is taking clopidogrel plus one or more additional medications metabolised by CYP2C19, then that person may have altered metabolism of clopidogrel and the other drugs. One of the prominent examples of drugs that are metabolised 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 personalised medicine known as pharmacogenomics. It is a relatively new field of study developed in an effort to treat individuals' conditions effectively, yet avoid side effects.
Is this test different than a platelet function test?
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/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 considered for those taking or considering a drug that may be influenced by the activity of the CYP2C19-related enzymes. Currently, there is no consensus on who should be tested. In some cases, a healthcare professiona may recommend that family members of a poor metaboliser consider testing so that this information is on record.
Can clopidogrel resistance testing be done in my doctor's surgery?
No, it requires specialised 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 healthcare professionals about my CYP2C19 test results?
Yes, this would be good information for them to have, regardless of whether you are currently taking clopidogrel.
Should I tell my healthcare professionals that I am taking clopidogrel?
Yes, it is crucial for you to tell all of your healthcare professionals 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.
Elsewhere on the Web
NICE British National Formulary page on Clopidogrel
NICE guidance on use of antiplatelet drugs
Genetic Home Reference: The CYP gene family
Genetic Home Reference: What is pharmacogenomics?
British Heart Foundation: antiplatelet drugs