Key result
Carriage of mutant alleles CYP3A5*3 and CYP2C19*2 was associated with lower platelet inhibition and a significantly higher frequency of ischemic event relapse within 6 months post-PCI.
Why the study?
Do genetic polymorphisms of cytochrome P450 enzymes affect the efficacy of clopidogrel in preventing ischemic events in Chinese patients after PCI?
Observational (n=118)
No
Do genetic polymorphisms of cytochrome P450 enzymes affect the efficacy of clopidogrel in preventing ischemic events in Chinese patients after PCI?
Absolute Event Rate: 31.33% vs 54.68%
p-value: p=<0.05
Genetic polymorphisms of CYP3A5*3 and CYP2C19*2 significantly reduce the antiplatelet efficacy of clopidogrel and increase the risk of ischemic relapse in Chinese patients after PCI.
May flag CYP3A5*3/CYP2C19*2 carriers at higher ischemic risk on clopidogrel post-PCI; leaves open genotype-guided trials.
We investigated the correlation between genetic polymorphisms of cytochrome P450 enzyme genes and the outcome of clopidogrel treatment in 118 coronary disease patients after percutaneous coronary intervention at the Chinese PLA General Hospital. Patients were divided into an ischemia event relapse group (IERG) and a non-IERG group (NIERG) based on relapse of ischemia events within 6 months after percutaneous coronary intervention. Ischemia occurred in 26.27% of patients. Thromboelastogram platelet mapping results showed that compared with the NIERG, the ADP-induced platelet inhibition ratio in the IERG was significantly lower (31.33 ± 24.91% vs 54.68 ± 26.63%, P < 0.05). The platelet inhibition ratio of patients carrying mutant alleles CYP3A5*3 (41.98 ± 29.33% vs 52.89 ± 26.49%), CYP2C19*2 (43.15 ± 27.97% vs 55.89 ± 26.71%), and P2Y12*1 (38.74 ± 24.36% vs 52.19 ± 28.58%) was lower than patients with the wild-type alleles. The frequency of ischemia event relapse in patients with the mutant alleles CYP3A5*3 and CYP2C19*2 was significantly higher than patients carrying the G/G genotype; however, there was no significant difference between patients carrying the T/T genotype and C allele of P2Y12*1. Thus, coexisting polymorphisms of CYP3A5*3 and 2C19*2, but not P2Y12*1, play an important role in the variability of clopidogrel's curative effect.
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Sun et al. (2015) conducted an observational in Coronary disease (n=118). Genetic polymorphisms of CYP3A5*3 and CYP2C19*2 vs. Wild-type alleles was evaluated on ADP-induced platelet inhibition ratio (ischemia event relapse group vs non-relapse group) (p=<0.05). Carriage of mutant alleles CYP3A5*3 and CYP2C19*2 was associated with lower platelet inhibition and a significantly higher frequency of ischemic event relapse within 6 months post-PCI.
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