Clopidogrel is a drug which is often used to treat heart attacks, in combination with aspirin. It acts by blocking certain receptors on blood particles called platelets, making them less likely to form clots in the coronary arteries that supply the heart. In some people, clopidogrel does not appear to work, and this phenomenon is known as clopidogrel resistance. Although the term clopidogrel resistance sounds as if it refers to one specific mechanism, there are really several reasons why the drug may fail to work for a given individual. Resistance is different from failure of therapy, where a drug has produced the correct reaction in the body but the patient's disease recurs due to other factors.
As it helps to prevent the formation of blood clots, clopidogrel is given to people who have had a heart attack or stroke to prevent recurrences. It may be given in combination with aspirin following procedures to open blocked arteries. These could include balloon angioplasty, where a balloon is inflated inside an artery, and stenting, where a tube is inserted to hold open a blood vessel. Patients with clopidogrel resistance may have an increased risk of complications after these operations. Other uses of clopidogrel include treating the chest pain that is associated with heart attacks and the condition known as angina, where the heart's blood supply is inadequate.
Before clopidogrel can take effect in the body it needs to be absorbed from the gut into the blood stream. Next it must be converted into its active form by enzymes in the liver. If patients have a condition which prevents the drug from being absorbed properly, this could result in clopidogrel resistance. In some patients, the required liver enzymes may not function normally, so that less clopidogrel is converted to the active form, making the drug less effective. Clopidogrel drug interactions can occur when other drugs taken at the same time use the same enzymes, resulting in lower availability of the active form of clopidogrel.
For some cases of clopidogrel resistance, increasing the clopidogrel dosage can make the drug more effective, but the higher dose may also lead to side effects occurring. Side effects of clopidogrel can include joint pain, abnormal bleeding, diarrhea and abdominal discomfort. Research is continuing into clopidogrel resistance and newer, more effective treatments are being investigated. Genetic testing could also reveal which patients have abnormally functioning versions of the liver enzymes responsible for clopidogrel conversion.