Impact of cytochrome P450 2C19*2 polymorphism on intra-stent thrombus assessed by follow-up optical coherence tomography in Chinese patients receiving clopidogrel.

Abstract

Cytochrome P450 (CYP) 2C19*2 polymorphism is associated with poor responsiveness to clopidogrel in patients undergoing percutaneous coronary intervention. Despite high frequency of this genetic variant in Chinese patients, its contribution to intra-stent thrombi assessed by optical coherence tomography (OCT) and major adverse cardiac events (MACE) remains unclear. A total of 198 patients who underwent follow-up OCT and simultaneous testing of CYP2C19 genotype by TaqMan assay and P2Y12 reaction unit (PRU) by VerifyNow P2Y12 assay were selected for the study. The patients were divided into three groups: non-carriers (*1/*1), carriers with one CYP2C19*2 allele (*1/*2), carriers with two CYP2C19*2 alleles (*2/*2). OCT data and MACE were compared among the three groups. The mean follow-up interval from coronary stent implantation to OCT was 360 ± 42 days, intra-stent thrombi were detected in 50 (25.2 %) patients (16.1 % for *1/*1, 27.8 % for *1/*2 and 43.8 % for *2/*2 carriers, p = 0.007). There were significantly increased PRU values among *1/*1, *1/*2 and *2/*2 carriers (200.4 ± 36.4 vs. 216.7 ± 44.6 vs. 242.8 ± 42.4, p < 0.001), as well as markedly decreased P2Y12 percent inhibition (38.6 ± 12.6 vs. 31.3 ± 13.1 vs. 23.8 ± 9.8 %, p < 0.001). Multivariate logistic regression analysis showed that the presence of CYP2C19 *2/*2 was the only independent predictor for intra-stent thrombi on OCT (OR: 3.488, 95 % CI: 1.992-9.046; p = 0.001), although both *1/*2 and *2/*2 were independent predictors for high on-clopidogrel platelet reactivity. CYP2C19*2/*2 homozygous status is associated with subclinical intra-stent thrombi in clopidogrel-treated Chinese patients.

• Authors: Shan Li, Yang Shi, Haijun Wang, Wei Zhang, Jianfeng Liu
• Journal: Journal of thrombosis and thrombolysis (J Thromb Thrombolysis) Vol. 40 Issue 1 Pg. 88-96 (Jul 2015) ISSN: 1573-742X [Electronic] Netherlands
• PMID: 25800884 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Platelet Aggregation Inhibitors
• Clopidogrel
• CYP2C19 protein, human
• Cytochrome P-450 CYP2C19
• Ticlopidine

Topics

• Aged
• Asian People (genetics)
• Clopidogrel
• Cytochrome P-450 CYP2C19 (genetics)
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Platelet Aggregation Inhibitors (pharmacology, therapeutic use)
• Polymorphism, Genetic (genetics)
• Retrospective Studies
• Stents (adverse effects)
• Thrombosis (diagnosis, drug therapy, genetics)
• Ticlopidine (analogs & derivatives, pharmacology, therapeutic use)
• Tomography, Optical Coherence (trends)