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经皮冠状动脉介入治疗（PCI）和冠状动脉支架植入术后延长氯吡格雷治疗（>12个月）与<12个月的风险和获益。我们的主要目的是评估不同类型冠状动脉支架（裸金属支架、第一代药物洗脱支架和第二代药物洗脱支架）的死亡或心肌梗死风险。我们将使用VA管理和临床数据库创建2002-2007年期间接受裸金属和第一代药物洗脱支架的两个患者队列，以及2008- 2010年期间接受第二代药物洗脱支架的第二个更现代的患者队列。我们的数据将来自VA国家患者护理数据库，其中包含来自患者治疗文件（PTF）和门诊诊所（OPC）文件的住院和门诊详细信息。将从VHA生命状态文件中获得人口统计学数据。将从药房福利管理系统文件中获取药房数据，包括用于估计治疗持续时间的药物处方。在2008-2010年队列中，我们还将从VA心血管评估报告和跟踪（CART）数据库中获得关于手术特征（例如支架长度、直径、支架数量、植入的动脉）的数据作为协变量。对于每种支架类型，我们将使用里程碑分析策略和考克斯比例风险回归来评估接受氯吡格雷长期治疗> 12个月与<12个月患者的死亡或心肌梗死风险。我们还将评估长期氯吡格雷治疗对心源性死亡、缺血性卒中、经皮冠状动脉介入治疗（PCI）或冠状动脉搭桥术的冠状动脉血运重建和大出血等次要终点的风险。作为次要目的，我们将通过合并两个队列来评价长期氯吡格雷与药物洗脱支架类型（第1代或第2代）的相互作用。使用相同的方法，我们将评估因其他适应症（如房颤）而长期抗凝治疗的患者亚组中氯吡格雷延长给药的风险。为了评估潜在的数据限制，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因素和适应症混杂因素的潜在影响：1.传统的多变量调整，2。倾向评分调整匹配分析; 3.队列仅限于具有低风险特征的患者。我们还将进行敏感性分析，以评估缺失协变量数据的影响。探索性分析将评估在PCI术后18个月、24个月和36个月的里程碑之后更长时间的氯吡格雷治疗的风险和获益。拟议的研究将提供有价值的信息，以弥补心脏病学界目前关于接受冠状动脉支架的退伍军人延长氯吡格雷治疗的风险和益处的信息差距。这些数据也可能为未来的随机试验提供信息，以解决长期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.