Prasugrel Therapy and CYP Genotype

Excerpt

Prasugrel (also known as Efient) is a third-generation thienopyridine platelet inhibitor used in individuals with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Prasugrel is prescribed to reduce thrombotic cardiovascular events, such as stent thrombosis, myocardial infarction, and stroke in these individuals. Along with other antiplatelet agents such as clopidogrel and ticagrelor, prasugrel inhibits platelet activation by irreversibly binding to the platelet receptor, P2RY12. (1)

Prasugrel is metabolized into its active metabolite primarily by CYP3A5 and CYP2B6, and to a lesser extent by CYP2C9 and CYP2C19. The FDA-approved label for prasugrel states that genetic variations in CYP2B6, CYP2C9, CYP2C19, or CYP3A5 genes do not significantly affect prasugrel’s pharmacokinetics, the generation of its active metabolite, or its inhibition of platelet aggregation in healthy subjects, individuals with stable atherosclerosis, or those with ACS (1).

Another commonly prescribed antiplatelet agent is the second-generation thienopyridine clopidogrel, which is bioactivated primarily by CYP2C19. As a result,, clopidogrel is less effective in individuals with decreased or non-function variant alleles of the CYP2C19 gene. In contrast, CYP2C19 variants do not decrease the effectiveness of prasugrel, which is a more potent antiplatelet agent compared to clopidogrel, though it carries a higher risk of bleeding (2, 3, 4, 5).