氯吡格雷抵抗与老年急性冠状动脉综合征患者心血管事件相关性研究

Relationship between Clopidogrel Resistance and Major Adverse Cardiac Events in Elderly Patients with Acute Coronary Syndrome

目的探讨氯吡格雷抵抗对高龄老年急性冠状动脉综合征患者长期心血管事件的影响。方法选择2009年1月-2010年12月入住解放军总医院心内科病房300例急性冠状动脉综合征患者为研究对象,年龄70～95岁,平均（81.3±6.4）岁。所有研究对象均接受氯吡格雷片75 mg,1次/d,至少服用1个月以上,采用以二磷酸腺苷作为底物的光比浊法检测患者服用氯吡格雷前和服用7 d后血小板聚集率的变化情况。按照血小板聚集率变化情况进行试验分组,血小板聚集率降低程度〈10%为氯吡格雷抵抗组,≥10%为氯吡格雷非抵抗组。随访主要心血管不良事件（包括心血管病死亡、非致死性心肌梗死、再发心绞痛、缺血性脑卒中/短暂性脑缺血发作、急性血栓形成及出血并发症）的发生情况,随访中位时间为2年。采用Cox风险回归模型评估氯吡咯雷抵抗与心血管事件的关系。结果氯吡格雷抵抗的发生率为24.0%。患有糖尿病、肾功能不全及体质量指数增高患者易于发生氯吡格雷抵抗,氯吡格雷抵抗患者心血管主要不良事件发生率明显增加（37.5%、22.8%,P=0.032）,Cox风险回归方程提示氯吡格雷抵抗是心血管事件发生的独立危险因素[HR=2.34,95%CI（1.07,4.57）,P=0.016]。结论老年急性冠状动脉综合征患者糖尿病、肾功能不全及体质量指数增高与氯吡格雷抵抗相关,氯吡格雷抵抗患者发生心血管不良事件的风险明显增加。

Objective To investigate the impact of clopidogrel resistance on the long-term prognosis in the elderly with acute coronary syndrome（ACS）, as clopidogrel is widely used for secondary prevention in the patients with ACS, while studies on the relationship between clopidogrel resistance and long-term outcome in the elderly with ACS are limited. Methods Three hundred elderly patients with ACS, aged from 70 to 95, with on average age of（81.3 ± 6.4） years old, receiving clopidogrel（75 mg, once a day） over one month between January 2009 and December 2010 were followed up for major adverse cardiac events（MACE, including cardiac death, non-fatal re-myocardial infarction, angina, ischemia stroke/TIA, acute thrombosis and hemorrhage）. Platelet aggregation was measured by light transmission aggregometry using adenosine diphosphate as a stimulus. According to the variation of platelet aggregation, the patients were divided into clopidogrel resistance group（ 〈10%） and nonlopidogrel resistance group（ ≥ 10%）. The median follow-up was 2 years. A Cox hazard proportional model was used to estimate time to outcome associated with clopidogrel resistance and MACE. Results The incidence of clopidogrel resistance was 24.0% in our study population. Patients with diabetes, renal insufficiency, or a higher body mass index tended to have clopidogrel resistance. Compared with those patients without clopidogrel resistance, there was significantly increased MACE in patients with clopidogrel resistance（37.5%, 22.8%; P=0.032）. Additionally, Cox hazard proportional model analysis demonstrated that clopidogrel resistance was an independently risk factor for MACE [HR=2.34, 95% CI（1.07, 4.57）, P=0.016]. ConclusionDiabetes, renal insufficiency and high body max index are associated with clopidogrel resistance, which can predict the increased risk of MACE in elderly patients with ACS.