Departments of Hematology, AIIMS, New Delhi – 110029, India.
Platelets. 2013;24(4):297-302. doi: 10.3109/09537104.2012.693992. Epub 2012 Jun 21.
Aspirin and Clopidogrel are used in prophylaxis of patients undergoing percutaneous coronary intervention and long-term prevention of cardiovascular and cerebrovascular events. Clopidogrel resistance has been attributed to P2Y1 and P2Y12 adenosine diphosphate (ADP) receptor polymorphisms. This study enrolled 100 patients of coronary artery disease (CAD) who were on the maintenance dose of clopidogrel (75 mg OD) with or without aspirin. In addition, 10 received loading dose (300 mg) prior to percutaneous coronary intervention. Relevant clinical and drug history were elicited. ADP-induced platelet aggregation study and PCR-RFLP for P2Y1 (1622A > G) and P2Y12 (i-T744C) polymorphisms were performed. Two groups of controls were used for defining cut-off for platelet aggregation response. Follow-up data, wherever available was recorded. The most common pattern of aggregation response was disaggregation, either complete (46.4%) or partial (53.6%). A frequency of 13% clopidogrel non-responders and 19% semi-responders was found. All the cases were H1/H1 haplotype for P2Y12 gene polymorphism and 28 (29.2%) patients carried P2Y1 1622A > G (21(21.9%) AG and 7(7.3%) GG) gene polymorphism, the frequency being greater in clopidogrel responders compared to semi/non-responders but difference was not statistically significant. There was no statistically significant difference between responders and semi/non-responders in terms of the history of risk factor for CAD, concurrent atorvastatin use or past history of an acute vascular event. On follow up, the two patients who developed myocardial infarction/acute coronary syndromes (MI/ACS) were clopidogrel semi- and non-responder, respectively. Variability in clopidogrel response with 13% non-responders and 19% semi-responders was seen in this study with adverse outcome (MI/ACS) on follow up seen in two patients. Hence, poor response to clopidogrel may be related to increased likelihood of adverse long-term coronary event that may benefit from additional or alternative anti-platelet therapy. Clopidogrel resistance was not associated with ADP receptor P2Y1 and P2Y12 gene polymorphisms. Hence, it is postulated that clopidogrel resistance in CAD patients is multifactorial and not caused by single-gene polymorphisms.
阿司匹林和氯吡格雷用于经皮冠状动脉介入治疗患者的预防和长期心血管和脑血管事件的预防。氯吡格雷抵抗归因于 P2Y1 和 P2Y12 二磷酸腺苷（ADP）受体多态性。本研究纳入了 100 例接受氯吡格雷（75mg OD）维持剂量治疗的冠心病（CAD）患者，其中部分患者还服用阿司匹林。此外，10 例患者在经皮冠状动脉介入治疗前接受了负荷剂量（300mg）。记录相关的临床和药物史。进行 ADP 诱导的血小板聚集研究和 PCR-RFLP 分析，以检测 P2Y1（1622A>G）和 P2Y12（i-T744C）多态性。使用两组对照来确定血小板聚集反应的截止值。记录所有可用的随访数据。最常见的聚集反应模式是解聚，无论是完全（46.4%）还是部分（53.6%）。发现氯吡格雷无反应者和半反应者的频率分别为 13%和 19%。所有患者均为 P2Y12 基因多态性的 H1/H1 单倍型，28 例（29.2%）患者携带 P2Y1 1622A>G （21（21.9%）AG 和 7（7.3%）GG）基因多态性，与半反应者/无反应者相比，氯吡格雷反应者的频率更高，但差异无统计学意义。在 CAD 危险因素史、阿托伐他汀同时使用或既往急性血管事件史方面，反应者与半反应者/无反应者之间无统计学差异。在随访中，两名发生心肌梗死/急性冠状动脉综合征（MI/ACS）的患者分别为氯吡格雷半反应者和无反应者。本研究中，氯吡格雷反应性存在 13%的无反应者和 19%的半反应者，随访中出现了两名患者的不良结局（MI/ACS）。因此，氯吡格雷反应不良可能与不良的长期冠状动脉事件的发生几率增加有关，这些患者可能受益于额外或替代的抗血小板治疗。氯吡格雷抵抗与 ADP 受体 P2Y1 和 P2Y12 基因多态性无关。因此，推测 CAD 患者的氯吡格雷抵抗是多因素的，而不是由单个基因突变引起的。
