Golukhova Elena Z, Ryabinina Mariya N, Bulaeva Naida I, Grigorian Marina V, Kubova Maida Ch, Serebruany Victor L
1Bakoulev Center for Cardiovascular Surgery, Department of Nonivasive Cardiology, Moscow, Russia; and 2HeartDrug™ Research Laboratories, Johns Hopkins University, Towson, MD.
Am J Ther. 2015 May-Jun;22(3):222-30. doi: 10.1097/MJT.0000000000000125.
The aim of this study was to triage platelet reactivity and adverse vascular outcomes after dual antiplatelet therapy due to percutaneous coronary intervention (PCI) dependent on CYP2C192 and CYP2C193 genotypes in patients with coronary artery disease. Fifty-five patients with coronary artery disease were studied serially pre-PCI and post-PCI. Platelet reactivity was assessed by conventional light transmission aggregometry, VerifyNow Analyzer, and thromboelastography with platelet mapping. Genetic testing was performed with allele-specific real-time polymerase chain reaction. Adverse events included vascular death, acute myocardial infarction, repeated PCI, definite stent thrombosis, and angina recurrence. The common genotype (GG) was found in 39 patients, heterozygous polymorphism CYP2C19 (GA) G681A allele was detected in 14 patients, and the rare homozygous polymorphism CYP2C19 (AA) G681A allele was exhibited in 2 patients. There were no CYP2C193 (Trp212Ter) carriers among index patients. The platelet reactivity was higher in patients with heterozygous and homozygous carriers compared with GG genotype. The largest differences were observed among GG, GA, and AA genotypes, which correlated with the average values of platelet aggregation (P = 0.02). There was a significant link between adverse events and high platelet reactivity assessed by light transmission aggregometry (P = 0.002). We found a trend between different genotype and VerifyNow readings (P = 0.057); moreover, their cumulative impact on adverse events was significant (P = 0.041). Platelet reactivity is higher in patients with heterozygous and homozygous carriers of CYP2C192 versus common genotype and may predict an increased risk of clopidogrel response variability and/or experiencing adverse cardiac events.
本研究旨在根据冠心病患者的CYP2C192和CYP2C193基因型，对经皮冠状动脉介入治疗（PCI）后双联抗血小板治疗的血小板反应性和不良血管结局进行分类。对55例冠心病患者在PCI术前和术后进行了连续研究。通过传统的光透射聚集法、VerifyNow分析仪和带有血小板图谱的血栓弹力图评估血小板反应性。采用等位基因特异性实时聚合酶链反应进行基因检测。不良事件包括血管性死亡、急性心肌梗死、重复PCI、明确的支架血栓形成和心绞痛复发。39例患者为常见基因型（GG），14例患者检测到杂合多态性CYP2C19（GA）G681A等位基因，2例患者表现为罕见的纯合多态性CYP2C19（AA）G681A等位基因。入选患者中无CYP2C193（Trp212Ter）携带者。与GG基因型相比，杂合子和纯合子携带者患者的血小板反应性更高。在GG、GA和AA基因型之间观察到最大差异，这与血小板聚集的平均值相关（P = 0.02）。通过光透射聚集法评估，不良事件与高血小板反应性之间存在显著关联（P = 0.002）。我们发现不同基因型与VerifyNow读数之间存在一种趋势（P = 0.057）；此外，它们对不良事件的累积影响是显著的（P = 0.041）。与常见基因型相比，CYP2C192杂合子和纯合子携带者患者的血小板反应性更高，可能预示着氯吡格雷反应变异性增加和/或发生不良心脏事件的风险增加。
