The influence of CYP2C19*2 and*17 on on-treatment platelet reactivity and bleeding events in patients undergoing elective coronary stenting

作者：Harmsze Ankie M; van Werkum Jochem W; Hackeng Christian M; Ruven Hendrik J T; Kelder Johannes C; Bouman Heleen J; Breet Nicoline J; ten Berg Jurrien M; Klungel Olaf H; de Boer Anthonius; Deneer Vera H M^*

来源：Pharmacogenetics and Genomics, 2012, 22(3): 169-175.

DOI：10.1097/FPC.0b013e32834ff6e3

• bleedings
• clopidogrel
• CYP2C19
• metabolism
• pharmacogenetics
• platelet reactivity

Objectives To investigate the impact of genotypes on the basis of the loss-of-function variant CYP2C19*2 and the gain-of-function variant CYP2C19*17 on on-treatment platelet reactivity and on the occurrence of Thrombolysis in Myocardial Infarction (TIMI) major bleedings in 820 clopidogrel-treated patients who underwent elective coronary stenting.
Methods On-treatment platelet reactivity was quantified using ADP-induced light transmittance aggregometry (LTA) and the VerifyNow P2Y12 assay. Postdischarge TIMI major bleedings within 1 year after enrollment were recorded.
Results In total, 25 major bleedings (3.0% of the study population) were observed. Patients with the CYP2C19*117 and *1717 diplotypes exhibited a lower magnitude of platelet reactivity as compared with patients with the CYP2C19*11 diplotype (for the light transmittance aggregometry-adjusted mean difference: -5.8%, 95% confidence interval: -9.6 to -2.1, P = 0.002). Patients with the *117 and *1717 genotype had a 2.7-fold increased risk in the occurrence of major bleedings [adjusted hazard ratio: 2.7, 95% confidence interval: 1.1-7.0, P = 0.039]. The diplotypes *217, *12, and *22 exhibited higher on-treatment platelet reactivity as compared with the wild type (P<0.0001). However, this was not translated into an altered risk on major bleedings as compared with the wild type [hazard ratio: 1.3 (0.45-4.0), P = 0.60]. Results have not been adjusted for multiple testing.
Conclusion Patients with the CYP2C19*117 and *1717 diplotype have a lower magnitude of on-treatment platelet reactivity and are at a 2.7-fold increased risk of postdischarge TIMI major bleeding events after coronary stenting than patients with the *11 genotype. The diplotypes *217, *12, and *22 are associated with increased on-treatment platelet reactivity; however, this is not translated into a lower risk of bleeding events.

• 出版日期2012-3