What is the risk for a patient with a CYP2C19 *2/*3 genotype receiving clopidogrel in terms of adverse cardiovascular events?

Patients with a CYP2C19 *2/*3 genotype are at an increased risk for adverse cardiovascular events when receiving clopidogrel. This is due to the role of the CYP2C19 enzyme in the metabolism of clopidogrel, which is a prodrug that requires conversion to its active form for effectiveness.

Individuals with the *2/*3 genotype typically exhibit reduced or absent enzyme function, resulting in decreased formation of the active metabolite of clopidogrel. As a consequence, these patients may have a suboptimal therapeutic response to clopidogrel, which can lead to inadequate platelet inhibition. This inadequacy can manifest as a heightened risk for adverse cardiovascular events, such as stent thrombosis or recurrent myocardial infarction, particularly in the context of acute coronary syndrome or following percutaneous coronary interventions.

The increased cardiovascular risk associated with this genotype underscores the importance of genetic testing in patients being prescribed clopidogrel. It can guide therapeutic decisions, including the consideration of alternative antiplatelet agents that do not rely on CYP2C19 metabolism, thereby potentially improving clinical outcomes.