Effect of CYP2C19*2 and *17 Genetic Variants on Platelet Response to Clopidogrel and Prasugrel Maintenance Dose and Relation to Bleeding Complications

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• 作者：Charlotte Grosdidier ; MD^a ; ^b ; Jacques Quilici ; MD^b ; ^c ; Marie Loosveld ; MD^a ; ^b ; ^d ; Laurence Camoin ; PhD^a ; ^b ; ^d ; Pierre Julien Moro ; MD^b ; ^c ; Noé ; mie Saut ; PhD^a ; ^b ; Bé ; né ; dicte Gaborit ; MD^a ; ^b ; Mathieu Pankert ; MD^b ; ^c ; William Cohen ; MD^a ; ^b ; ^d ; Marc Lambert ; MD^b ; ^c ; Shirley Beguin ; PhD^e ; Pierre Emmanuel Morange ; MD ; PhD^a ; ^b ; ^d ; Jean-Louis Bonnet ; MD^a ; ^b ; ^c ; Marie-Christine Alessi ; MD ; PhD^b ; ^c ; ^d ; Thomas Cuisset ; MD ; PhD^a ; ^b ; ^c ; ^{thomas.cuisset@ap-hm.fr}
• 刊名：The American Journal of Cardiology
• 出版年：2013
• 出版时间：1 April, 2013
• 年：2013
• 卷：111
• 期：7
• 页码：985-990
• 全文大小：386 K

文摘

The present study was performed to compare the influence of cytochrome P459 2C19 (CYP2C19) *2 and *17 genetic variants on the platelet response to clopidogrel and prasugrel maintenance therapy and to assess the relation between platelet reactivity and bleeding complications. A total of 730 patients were included (517 patients treated with clopidogrel 150 mg/day and 213 discharged with prasugrel 10 mg). Platelet reactivity was assessed at 1 month with the platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP). High on-treatment platelet reactivity was defined as PRI VASP >50 % and low on-treatment platelet reactivity (LTPR) as PRI VASP <20 % . The patients were classified according to their genotypes as poor metabolizers (*2/non *17), intermediate metabolizers (*2/*17 or non *2/non *17) and ultrametabolizers (non *2/*17). At 1 month, the prasugrel response was significantly better than the clopidogrel response in all groups of patients, with a lower incidence of high on-treatment platelet reactivity but a greater incidence of LTPR, regardless of the genetic variants. The genetic distribution had a significant effect on the mean PRI VASP values, the incidence of high on-treatment platelet reactivity, and LTPR with both clopidogrel and prasugrel (p <0.05 for all). LTPR identified a group of patients at a greater risk of bleeding (odds ratio 4.8, 95 % confidence interval 2.7 to 8.3; p <0.0001). In conclusion, the present study showed that both clopidogrel and prasugrel have genetic modulation by CYP2C19 *2 and *17 alleles and that prasugrel provides greater platelet inhibition, regardless of the genotypes. In addition, LTPR was associated with a greater risk of bleeding.