以血栓弹力图定义的阿司匹林及氯吡格雷双药抵抗对经皮冠状动脉介入治疗远期预后的评估价值

Value of Aspirin and Clopidogrel Resistance in Evaluating Long-term Prognosis After Percutaneous Coronary Intervention

目的 :探索以血栓弹力图定义的阿司匹林及氯吡格雷双药抵抗对经皮冠状动脉介入治疗(PCI)远期预后的评估价值。方法:纳入2013年1月至2013年12月在阜外医院进行PCI治疗并行血小板功能检测的患者共6 785例,分析阿司匹林及氯吡格雷双药抵抗发生的风险因素。同时符合阿司匹林抵抗及氯吡格雷抵抗标准的患者为双药抵抗组(n=385),其余患者纳入非双药抵抗组(n=6 400)。进行2年随访,记录主要不良心脑血管事件(MAACE),比较抗血小板药物抵抗和非抵抗患者的临床预后。结果:6 785例患者中,同时符合阿司匹林及氯吡格雷双药抵抗的患者共385例(5.67%)。双药抵抗组与非双药抵抗组相比,女性患者(28.1%vs 22.1%)及ST段抬高型心肌梗死(STEMI)的比率更高(15.6%vs 11.3%),术前血红蛋白水平更低(g/L,141.12±15.72vs 137.54±15.41)、血清总胆固醇、低密度脂蛋白胆固醇以及高敏C反应蛋白(hs-CRP)水平更高(P均<0.01)。2年随访结果显示,MAACE及出血事件的发生率两组间无统计学差异。Logistic单因素回归分析提示,女性(OR=1.37,95%CI:1.09~1.73)、hs-CRP升高、总胆固醇和低密度脂蛋白胆固醇升高以及发生STEMI、术前血红蛋白水平降低(OR=0.99,95%CI:0.98~0.99)是发生阿司匹林及氯吡格雷双药抵抗的风险预测因素。但多因素回归分析提示,仅术前血红蛋白水平与双药抵抗发生风险相关(OR=0.99,95%CI:0.98~1.00)。Cox多因素回归分析显示,阿司匹林及氯吡格雷双药抵抗不是全因死亡、心原性死亡、心肌梗死、再次血运重建、支架血栓、再发卒中、出血事件(HR=0.95,95%CI:0.62~1.45)和MACCE(HR=0.99,95%CI:0.73~1.35)的危险因素。结论:本研究阿司匹林及氯吡格雷双药抵抗的发生率为5.67%,其发生可能与性别、血脂水平及血清炎症水平升高有关。长期随访显示,阿司匹林及氯吡格雷双药抵抗与出血事件及MACCE的发生并无相关性。

Objectives: The aim of this study is to define the possible predictive value of aspirin and clopidogrel resistance in percutaneous coronary intervention(PCI) patients, on the long-term clinical outcomes. Methods: From January 2013 to December 2013, 6 785 patients underwent PCI and platelet function tests were enrolled. The risk factors of aspirin and clopidogrel resistance were analyzed. There were 385 patients with both aspirin and clopidogrel resistance, and 6 400 patients without both aspirin and clopidogrel resistance(non-resistance group). The major adverse cardiovascular and cerebrovascular events(MACCE) were recorded during the 2 years follow-up and the clinical outcomes were compared between the two groups.Results: The overall incidence of aspirin and clopidogrel resistance were 5.67%. In the aspirin and clopidogrel resistance group, the proportion of women(28.1% vs 22.1%, P<0.01) and the rate of STEMI(15.6% vs 11.3%, P=0.01), the total cholesterol and low density lipoprotein cholesterol levels and the high sensitivity C reactive protein levels were significantly higher, while the preoperative hemoglobin level was lower(P<0.01) as compared to non-resistance group. Two years follow-up results showed that there was no statistical difference between the two groups on MACCE and bleeding events. Logistic single factor regression analysis indicated that the risk factors for the aspirin and clopidogrel resistance included female(OR=1.37, 95%CI: 1.09~1.73), increased high sensitivity C reactive protein and total cholesterol and low density lipoprotein levels, STEMI and lower preoperative hemoglobin level(OR=0.99, 95%CI: 0.98~0.99). However, multivariate regression analysis showed that except for the level of hemoglobin(OR=0.99, 95%CI: 0.98~1.00), other indicators were not risk predictors of aspirin and clopidogrel resistance. COX multiple regression analysis showed that aspirin and clopidogrel resistance were not the risk factor for all-cause death, cardiac death, myocardial infarction, revascularization, stent thrombosis, recurrent stroke, bleeding(HR=0.95, 95%CI:0.62~1.45) and MACCE(HR=0.99, 95%CI: 0.73~1.35). Conclusions: This large cohort study results indicate that the incidence of aspirin and clopidogrel resistance of is 5.67%, which is related to sex, the level of blood lipid and serum inflammation factors. However, the long-term follow-up results show that aspirin and clopidogrel resistance is not linked with higher incidence of MACCE and bleeding events.