A case of resistance to clopidogrel and prasugrel after percutaneous coronary angioplasty

Excerpt

Dual antiplatelet therapy (aspirin and clopidogrel) is the standard therapy to prevent stent thrombosis after percutaneous coronary angioplasty. Clopidogrel is a prodrug which requires two-step activation through oxidative metabolism, involving various cytochrome P-450 (CYP) enzymes [1]. Carriers of defective alleles for CYP2C19 (*2) and CYP2C9 (*2, *3) have a reduced antiplatelet effect in response to clopidogrel [2, 3]. In addition, CYP3A4 in vivo activity measured by the erythromycin breath test is significantly correlated with the ability of clopidogrel to inhibit platelet aggregation [4]. Lastly, it has been reported that omeprazole and atorvastatin—which are inhibitors of CYP2C19 and CYP3A4, respectively—can reduce the effect of clopidogrel in man [5, 6]. Thus, there is clinical evidence that the activity of at least three cytochromes determines the effectiveness of clopidogrel in vivo. …