The Association of ABCB1, CYP2C19 and CYP2C9 Combined Activity with Clopidogrel Resistance in Patients with Recurrent Ischemic Stroke

Clopidogrel therapy is recommended to prevent recurrent ischemic stroke. However, clopidogrel resistance exists. This study examines which enzymes are involved in clopidogrel resistance. The study group includes 402 neurology patients who had experienced a recurrent ischemic stroke while receiving clopidogrel monotherapy. Patients were genotyped for CYP2C19, CYP2C9, CYP2B6, CYP3A4, CYP3A5, CYP1A2, ABCB1 and CES1A1. Phenotype frequencies were compared with those of a Global(G), European(E) and a local patient control(C) group. Only for ABCB1 a significant difference in phenotype distribution was seen (pG = 0.003, pE = <0.001, pC = 0.019). In patient with ABCB1 rapid efflux activity (3435TT), no other enzyme was significantly associated. In patients with ABCB1 normal efflux activity (3435CT/CC), CYP2C19 intermediate and poor metabolism were significantly associated (pE = <0.001, pG = <0.001, pC = 0.002). In patients with normal CYP2C19 metabolism, CYP2C9 intermediate and poor metabolism were significantly associated (pG = <0.001, pE = <0.001, pC = <0.001). Besides CYP2C19 clinical guidelines, also for ABCB1 and CYP2C9 guidelines are needed to prevent clopidogrel resistance.