J Cardiovasc Interv.  2022 Oct;1(4):168-179. 10.54912/jci.2022.0016.

Clinical Impact of Platelet Reactivity and Gene Polymorphisms in Patients With Ischemic Heart Disease After Percutaneous Coronary Intervention

• Lee SY
• Bae DH
• Kim M
• Lee DI
• Lee JH
• Kim SM
• Bae JW
• Hwang KK
• Kim DW
• Cho MC

• KMID: 2561256
• DOI: http://doi.org/10.54912/jci.2022.0016

Abstract

Background
Antiplatelet response of clopidogrel, as a pro-drug requiring CYP450 biotransformation, is not uniform in human. In this study, we aimed to evaluate the clinical impact of platelet reactivity, measured by platelet function test, and gene polymorphism, assessed by genotyping, in Korean patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).
Methods
We searched the database of Chungbuk Regional Cardiovascular Center from January 2010 to August 2014, and extracted the results from platelet function tests and genetic studies when Clopidogrel was initiated after conventional PCI in the setting of ischemic heart disease. High on-treatment platelet reactivity (HPR) was defined as P2Y12 reaction unit (PRU) ≥ 240.
Results
We enrolled 567 patients with CAD who underwent PCI. The level of PRU in CYP*2 heterozygotes, CYP*3 heterozygotes, CYP*2/*2, CYP*2/*3 and CYP*3/*3 (poor metabolizers [PMs], 243 ± 84.4) were significantly higher than CYP*1/*1 and CYP*1/*17 (extensive metabolizers [EMs], 209 ± 86.8, P = 0.006, one way ANOVA). At 1-year follow-up, major adverse cardiac events (MACEs) had occurred more frequently in patients with high on-treatment Clopidogrel platelet reactivity compared to those without high on-treatment clopidogrel platelet reactivity, but the difference did not reach a statistically significant level (23 [9.3%] vs. 27 [7.5%], P = 0.27). Kaplan-Meier test for MACE-free survival did not showed a significant difference in survival between high on-treatment Clopidogrel platelet reactivity and non-high on-treatment Clopidogrel platelet reactivity groups. At one-year follow-up, the incidence rate of MACE was similar between EMs (n = 19, 9.5%) and, PMs and IMs (n = 21, 8.4%; P = 0.73). Survival analysis revealed similar MACE rates among 3 clopidogrel metabolism groups.
Conclusions
In patients receiving clopidogrel after PCI, presence of even one reducedfunction CYP2C19 allele was associated with a significant increase in PRU level and high ontreatment Clopidogrel platelet reactivity. Future large-scale prospective studies are required to further validate our clinical results.

Keyword

Clopidogrel; Platelet; Gene polymorphisms