Clopidogrel resistance

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What is clopidogrel resistance?

Clopidogrel resistance is a condition in which the drug clopidogrel is less effective than normal in people who are treated with it. Clopidogrel (also known as Plavix) is an antiplatelet drug, which means that it prevents blood cell fragments called platelets from sticking together (aggregating) and forming blood clots. This drug is typically given to prevent blood clot formation in individuals with a history of stroke; heart attack; a blood clot in the deep veins of the arms or legs (deep vein thrombosis); or plaque buildup (atherosclerosis) in the blood vessels leading from the heart, which are opened by placement of a small thin tube (stent).

People with clopidogrel resistance who receive clopidogrel are at risk of serious, sometimes fatal, complications. These individuals may have another heart attack or stroke caused by abnormal blood clot formation; those with stents can develop blood clots (thromboses) within the stents, impeding blood flow.

People with clopidogrel resistance can be divided into two categories: intermediate metabolizers and poor metabolizers. Intermediate metabolizers are able to process some clopidogrel, so they receive partial benefit from the treatment but are not protected from developing a harmful blood clot. Poor metabolizers process little or no clopidogrel, so they receive very limited benefit from the treatment and are at risk of forming a harmful blood clot.

Clopidogrel resistance does not appear to cause any health problems other than those associated with clopidogrel drug treatment.

How common is clopidogrel resistance?

Clopidogrel resistance is a common condition, and its incidence can vary depending on ancestry. About half of individuals with Asian ancestry have clopidogrel resistance, with 10 percent of these individuals classified as poor metabolizers. Among people from western countries, nearly 30 percent are estimated to have clopidogrel resistance, with about 3 percent classified as poor metabolizers.

What genes are related to clopidogrel resistance?

Many genes are involved in converting clopidogrel to its active form and in determining the drug's effects in the body. The CYP2C19 gene is particularly important for the activation of clopidogrel, and certain common variations (polymorphisms) in this gene have been associated with clopidogrel resistance. CYP2C19 gene polymorphisms account for most of the variation in clopidogrel activation due to genetic factors. Polymorphisms in other genes likely have smaller effects on clopidogrel activation.

The CYP2C19 gene provides instructions for making an enzyme that is found primarily in liver cells. It is active in a cell structure called the endoplasmic reticulum, which is involved in protein processing and transport. The CYP2C19 enzyme plays a role in the processing of many drugs, including clopidogrel. The CYP2C19 enzyme helps to convert clopidogrel to its active form, which is necessary for the drug to function in the body. In its active form, clopidogrel prevents (inhibits) the function of a receptor protein known as P2RY12 that is found on the surface of platelets. During clot formation, the P2RY12 receptor protein helps platelets cluster together to form a clot to seal off damaged blood vessels and prevent blood loss. By inhibiting the function of the P2RY12 receptor, clopidogrel decreases the formation of blood clots, including clots that can cause heart attack, stroke, and deep vein thrombosis.

The two most common CYP2C19 gene polymorphisms associated with clopidogrel resistance (known as CYP2C19*2 and CYP2C19*3) result in the production of a nonfunctional CYP2C19 enzyme that cannot convert clopidogrel to its active form. Without active clopidogrel to interfere, the P2RY12 receptor continues to promote platelet aggregation and blood clot formation, which can lead to heart attacks, strokes, and thromboses in individuals with a history of these conditions.

In addition to changes in specific genes, many other factors, including gender, age, weight, diet, and other medications, play a role in how the body reacts to clopidogrel.

How do people inherit clopidogrel resistance?

Clopidogrel resistance is inherited in an autosomal codominant pattern. Codominance means that two different versions of the gene are active (expressed), and both versions influence the genetic trait. Some people with clopidogrel resistance have a reduced ability to convert the drug to its active form because of a polymorphism in one copy of the CYP2C19 gene that results in decreased enzyme activity. These individuals are described as intermediate metabolizers. Other individuals with clopidogrel resistance convert very little or none of the drug to its active form because of polymorphisms in both copies of the CYP2C19 gene, which results in a lack of enzyme activity. These individuals are described as poor metabolizers.

It is important to note that not all individuals with CYP2C19 gene mutations have clopidogrel resistance. These individuals who are at increased risk for developing clopidogrel resistance may or may not have a bad reaction when treated with the drug.

Where can I find information about diagnosis or management of clopidogrel resistance?

These resources address the diagnosis or management of clopidogrel resistance and may include treatment providers.

You might also find information on the diagnosis or management of clopidogrel resistance inEducational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about clopidogrel resistance?

You may find the following resources about clopidogrel resistance helpful. These materials are written for the general public.

MedlinePlus - Health information (5 links)
Educational resources - Information pages (7 links)
Patient support - For patients and families
National Blood Clot Alliance

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

ClinicalTrials.gov - Linking patients to medical research
PubMed - Recent literature
OMIM - Genetic disorder catalog

What other names do people use for clopidogrel resistance?

CYP2C19-related poor drug metabolism
poor metabolism of clopidogrel
resistance to clopidogrel

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about clopidogrel resistance?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding clopidogrel resistance?

acute ; atherosclerosis ; autosomal ; cell ; codominance ; coronary ; endoplasmic reticulum ; enzyme ;expressed ; gene ; heart attack ; incidence ; inherited ; metabolism ; pharmacogenetics ;pharmacogenomics ; plaque ; platelets ; polymorphism ; protein ; receptor ; syndrome ; thrombosis ;trait ; veins

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (5 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook