Prolonged Clopidogrel Use After Drug-Eluting and Bare-Metal Coronary Stenting

描述(由申请人提供)： 我们建议评估退伍军人接受经皮冠状动脉介入治疗(PCI)和冠状动脉支架置入术后，长期使用氯吡格雷(12个月)和12个月的风险和益处。我们的主要目标是根据冠状动脉支架的类型(裸金属支架、第一代药物洗脱支架和第二代药物洗脱支架)评估死亡或心肌梗死的风险。我们将使用VA管理和临床数据库创建2002-2007年间接受裸金属和第一代药物洗脱支架治疗的两组患者，以及2008-2010年间接受第二代药物洗脱支架治疗的第二组更现代的患者。我们的数据将来自退伍军人管理局国家患者护理数据库，该数据库包含患者治疗文件(PTF)和门诊(OPC)文件中有关住院和门诊患者详细信息。人口统计数据将从VHA生命状态文件中获得。药房数据将从药房福利管理系统文件中获得，包括估计治疗持续时间的药物处方。在2008-2010年的队列中，我们还将从退伍军人事务部心血管评估报告和跟踪(CART)数据库中获得程序特征(例如支架长度、直径、支架数量、动脉支架)作为协变量的数据。对于每种支架类型，我们将使用里程碑式的分析策略和考克斯比例风险回归来评估接受12个月氯吡格雷和12个月治疗的患者死亡或心肌梗死的风险。我们还将评估延长氯吡格雷治疗对心源性死亡、缺血性中风、冠状动脉介入治疗或冠状动脉旁路手术的冠状动脉血运重建术以及大出血的次要终点的风险。作为次要目标，我们将通过结合两个队列来评估延长氯吡格雷和药物洗脱支架类型(第一代或第二代)的相互作用。使用相同的方法，我们将评估因其他适应症(如心房颤动)而接受慢性抗凝治疗的患者亚组中氯吡格雷延长的风险。为了评估潜在的数据局限性，我们将在队列的子样本中进行图表审查，以验证几个关键协变量，如阿司匹林依从性。我们还将通过三种方法评估混杂和混杂的潜在影响：1.传统的多变量调整，2.倾向分数调整和匹配分析，3.将队列限制在低风险特征的患者。我们还将进行敏感性分析，以评估缺失协变量数据的影响。探索性分析将评估超过介入治疗后18个月、24个月和36个月这三个里程碑的更长时间的氯吡格雷治疗的风险和益处。这项拟议的研究将提供有价值的信息，弥合心脏病学界目前关于接受冠状动脉支架的退伍军人长期接受氯吡格雷治疗的风险和好处的信息鸿沟。这些数据也可能为未来的随机试验提供信息，以解决延长氯吡格雷治疗的价值。

DESCRIPTION (provided by applicant): We proposed to assess the risks and benefits of prolonged clopidogrel therapy (>12 months) versus <12 months among Veterans following percutaneous coronary interventions (PCI) with coronary stenting. Our primary aim is to assess the risk of death or myocardial infarction by type of coronary stent (bare-metal stents, 1st generation drug-eluting stents, and 2nd generation drug-eluting stents. We will use VA administrative and clinical databases to create two cohorts of patients receiving bare-metal and 1st generation drug-eluting stents between 2002-2007, and a second more contemporary cohort of patients receiving 2nd generation drug-eluting stents between 2008- 2010. Our data will be derived from the VA National Patient Care Database, which contains information on inpatient and outpatient details from the Patient Treatment Files (PTF) and Outpatient Clinic (OPC) files. Demographic data will be obtained from the VHA Vital Status file. Pharmacy data will be obtained from the Pharmacy Benefits Management system files, including medication prescriptions to estimate duration of therapy. In the 2008-2010 cohort we will also obtain data on procedural characteristics (e.g. stent length, diameter, number of stents, artery stented) as covariables from the VA Cardiovascular Assessment Reporting and Tracking (CART) database. For each stent type, we will use a landmark analysis strategy and Cox's proportional hazards regression to assess the risk of death or myocardial infarction in patients receiving prolonged clopidogrel > 12 months versus <12 months treatment. We will also evaluate the risk of prolonged clopidogrel therapy on the secondary endpoints of cardiac death, ischemic stroke, coronary revascularization with PCI or coronary artery bypass surgery, and major bleeding. As secondary aims, we will evaluate the interaction of prolonged clopidogrel and type of drug-eluting stent (1st or 2nd generation) by combining both cohorts. Using the same method, we will assess the risk of prolonged clopidogrel in subgroups of patients on chronic anticoagulation for other indications (e.g. atrial fibrillation). To evaluate potential data limitations we will perform chart reviews in a subsample of the cohorts to validate several key covariates, such as aspirin adherence. We will also evaluate the potential impact of confounding and confounding by indication by three methods: 1. Traditional multivariable adjustment, 2. Propensity score adjusted and matched analysis, 3. Restriction of the cohorts to patients with low risk characteristics. We will also conduct sensitivity analyses to assess the impact of missing covariate data. Exploratory analyses will evaluate the risks and benefits of more prolonged clopidogrel therapy beyond the landmarks of 18 months, 24 months and 36 months after PCI. The proposed research will provide valuable information to bridge the current information gap in the cardiology community regarding the risks and benefits of prolonged clopidogrel therapy in Veterans receiving coronary stents. These data may also inform future randomized trials to address the value of prolonged clopidogrel therapy.