Author + information
- Sang Yeub Lee,
- Sang Min Kim,
- Sang Min Kim,
- Ju-Hee Lee,
- Jang-Whan Bae,
- Kyung-Kuk Hwang,
- Dong-Woon Kim and
- Myeong-Chan Cho
Response to Clopidogrel, a pro-drug requiring CYP450 biotransformation, is not uniform. Current literature suggests that its pharmacologic effect varies based on CYP2C19 genotype, yet, there is uncertainty regarding the clinical impact of platelet function test and genotyping.
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 undergoing percutaneous coronary intervention (PCI).
We searched the database of Chungbuk Regional Cardiovascular Center from January 2010 to August 2014. We extracted the results from platelet function tests and genetic studies when Clopidogrel was initiated after conventional PCI in the setting of ischemic heart disease.
We enrolled 567 patients with coronary artery disease who underwent PCI. The level of P2Y12 reaction unit (PRU) in CYP*2 heterozygotes, CYP*3 heterozygotes, CYP*2/*2, CYP*2/*3 and CYP*3/*3 was significantly higher than CYP*1/*1 and CYP*1/*17 (209±86.8 (extensive metabolizers, EMs) vs 228±87.1 (intermediate metabolizers, IMs) vs 243±84.4 (poor metabolizers, PMs), p=0.006, one-way ANOVA). The frequency of high on-treatment Clopidogrel platelet reactivity (HPR) was also significantly higher in IMs and PMs (p=0.002). 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, yet, the difference did not reach a statistically significant level (23 (9.3%) vs 27 (7.5%), p=0.27). Platelet function was tested with VerifyNow P2Y12 assay. 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 (19 (9.5%)) and, PMs and IMs (21 (8.4%)) (p=0.73). Survival analysis revealed similar MACE rates between PMs, IMs and EMs.
In Korean patients receiving Clopidogrel after PCI, presence of even one reduced-function CYP2C19 allele was associated with a significant increase in PRU level and high on-treatment Clopidogrel platelet reactivity. However, neither the platelet reactivity nor gene polymorphisms could predict MACEs.