Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
J Atheroscler Thromb. 2010 Nov 27;17(11):1122-31. doi: 10.5551/jat.4564. Epub 2010 Aug 17.
Pre-procedural platelet reactivity (PR) in Korean patients may be greater because the CYP2C19*2 and *3 variant alleles are more common in Korean patients than in Caucasians. We investigated the level of PR and the prevalence of high post-clopidogrel platelet reactivity (HPPR) after a routine loading dose (LD) of clopidogrel in Korean patients.
We assessed the PR level at 12 to 24 hours after a 300-mg LD of clopidogrel in 215 patients undergoing scheduled percutaneous coronary intervention (PCI) (available CYP2C19 genotyping: n =176). PR was measured by conventional aggregometry and VerifyNow. Based on a previous study, HPPR was defined as a 5 µmol/L ADP-induced maximal PR >50%.
With 5 and 20 µmol/L ADP stimuli, maximal PR were 48.7 ± 17.1% and 62.1 ± 15.7%, respectively, and the prevalence of HPPR reached 52.1%. The highest quartile cut-offs of 5 and 20 µmol/L ADP-induced PR(max) were 64% and 75%, respectively. P2Y₁₂ reaction unit (PRU) was 274 ± 76, and 69.8% (n =150) showed PRU ≥240. A carrier of at least one CYP2C19 variant allele showed higher PRs than non-carriers. In multivariate regression analysis, carriage of the CYP2C19 variant allele (*2 or *3) was determined to be a significant predictor of HPPR (odds ratio 4.202, 95% confidence interval 1.996 to 8.850, p< 0.001).
Korean patients undergoing scheduled PCI cannot achieve adequate pre-procedural platelet inhibition from a 300-mg LD of clopidogrel, which is related with a higher prevalence of the CYP2C19 mutant allele.
由于 CYP2C19*2 和 *3 变异等位基因在韩国患者中比在高加索人群中更为常见,因此韩国患者的术前血小板反应性(PR)可能更高。我们研究了韩国患者接受常规负荷剂量(LD)氯吡格雷后 PR 水平和高氯吡格雷后血小板反应性(HPPR)的发生率。
我们评估了 215 例行择期经皮冠状动脉介入治疗(PCI)的患者(可进行 CYP2C19 基因分型:n=176)在服用 300mg 氯吡格雷 12 至 24 小时后的 PR 水平。PR 通过常规聚集测定法和 VerifyNow 进行测量。根据一项先前的研究,HPPR 定义为 5µmol/L ADP 诱导的最大 PR>50%。
用 5µmol/L 和 20µmol/L ADP 刺激时,最大 PR 分别为 48.7±17.1%和 62.1±15.7%,HPPR 发生率达到 52.1%。5µmol/L 和 20µmol/L ADP 诱导的 PR(max)的最高四分位数截止值分别为 64%和 75%。P2Y₁₂反应单位(PRU)为 274±76,69.8%(n=150)的 PRU≥240。至少携带一个 CYP2C19 变异等位基因的患者比非携带者的 PR 更高。在多变量回归分析中,携带 CYP2C19 变异等位基因(*2 或 *3)被确定为 HPPR 的显著预测因子(优势比 4.202,95%置信区间 1.996 至 8.850,p<0.001)。
接受择期 PCI 的韩国患者不能从氯吡格雷 300mg LD 获得充分的术前血小板抑制,这与 CYP2C19 突变等位基因的高发生率有关。