CYP2C19 Genetic Testing for Oral P2Y12 Inhibitor Therapy

Published: June 20, 2024

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  • Clopidogrel is the most prescribed oral P2Y12 inhibitor compared to others such as ticagrelor and prasugrel, to prevent ischemic outcomes in diseases such as coronary and peripheral artery disease and stroke, yet there are differences in mechanisms of action, efficacy, and safety to consider in the treatment decision.
  • Clopidogrel is administered as a prodrug that is mainly activated via the polymorphic hepatic cytochrome CYP2C219 enzyme, with the active drug able to inhibit platelet aggregation in the blood. Loss of function (LOF) variants in the CYP2C19 gene that encodes the enzyme are common, can be detected by genetic testing, and result in decreased drug activation, increased platelet aggregation, and are associated with increased ischemic events during clopidogrel therapy.
  • Ticagrelor and prasugrel are not dependent on CYP2C19 for activation but are more potent than clopidogrel and may result in increased risk of bleeding events during treatment. Thus, the treatment decision depends on selecting a drug that is active and can reduce the risk of ischemic events for the individual while also reducing the risk of bleeding events. This scientific statement provides evidence that prescribing ticagrelor or prasugrel to CYP2C19 LOF carriers identified through genetic testing while non-carriers are prescribed clopidogrel is a strategy that can reduce the risk of ischemia and bleeding.

Video: CYP2C19 Genetic Testing for Oral P2Y12 Inhibitor Therapy

Writing Group Chair Naveen Pereira, MD and Vice Chair Sharon Cresci, MD discuss a new scientific statement from the American Heart Association.