Clopidogrel

When we cut ourselves, the body responds with a complex physiological process that leads to blood clotting. The mechanisms present in the case of cuts or other injuries are meant to prevent blood loss, while blood clotting within intact vessels can lead to clogged arteries and heart or brain attacks. People who are subjected to unwanted blood clotting in the blood vessels take clopidogrel, a drug belonging to the thienopyridine class usually prescribed in combination with aspirin. Regular administration of clopidogrel prevents potential blood clotting, which could clog arteries and provoke a heart attack or a stroke. Clopidogrel is an antiplatelet drug because it works on platelets and prevents their aggregation. It is also used with people suffering from peripheral arterial disease, with those who have unstable angina as well as with those who have intracoronary stent.

The mechanism of clopidogrel activity

Clopidogrel is a therapeutic substance in the form of a pro-drug. This means that this substance needs the help of specific enzymes in the body to convert it to the active form otherwise the administration of clopidogrel has no effect. The aforementioned activation is primarily mediated through an enzyme called CYP2C19, which is found to be defective in more than a third of all Caucasians.

The effect of clopidogrel is insufficient or it has no effect on people who are carriers of a gene variant known as CYP2C19*2. These individuals have lower circulating concentrations of the active substance or don’t have it at all. Therefore, the risk of cardiovascular complications will not be reduced to the desired level after administrating the drug. FDA (US Food and Drug Administration) ordered the manufacturers of Plavix (with active ingredient of clopidogrel) to add a special warning on the medications, stating that the efficacy depends on the individual’s genotype and that for a certain group of people there will be no favourable therapeutic response to the treatment. Therefore various alternatives, such as aspirin monotherapy or adjunct use of other antithrombotic drugs (prasugrel, ticlopidine), are recommended for people with impaired CYP2C19. On the other hand, people with the gene variant known as CYP2C19*17 have an increased risk of bleeding upon clopidogrel administration. However, for the CYP2C19*17 genotype, there are no recommendations or guidelines for dosage modification nor have any alternative medications been suggested.