Stents and Antiplatelet Drugs: Impact on Ischemia and Bleeding in the Elderly

描述（由申请人提供）：冠心病是美国的主要死亡原因。老年人，即65岁以上的老年人，更有可能患冠心病，随着人口老龄化，这一问题将变得更加普遍。冠状动脉阻塞的支架植入术已经成为心脏病发作紧急情况下的常规技术，也是减少胸痛的常规治疗。一般来说，有两种类型的冠状动脉支架：药物涂层（或药物洗脱支架，DES）和非药物涂层（或裸金属支架，BMS）。放置任何一种类型的支架都需要用阿司匹林和氯吡格雷或普拉格雷等防止血栓形成的药物治疗，以保持支架的开放。后两种是较新类型的药物，与阿司匹林一起作用，以降低有助于在体内形成血凝块（血小板）的细胞的功能，从而防止支架上的凝块形成（支架血栓形成）。目前，美国心脏病学会/美国心脏协会建议在DES后继续使用这些药物至少一年，在BMS放置后至少一个月。比较DES和BMS的初步研究表明，通过减少支架周围的瘢痕形成，DES不太可能闭合并需要重复手术。这些研究招募的老年人有限，与社区居住的老年人相比，受试者通常更健康。尽管缺乏此类信息，但老年人在心脏手术期间常规接受DES，需要强制性使用一年的抗血小板药物。平均而言，老年人更有可能服用多种药物，体重较低，肾功能比随机试验中相对健康的人群更差，从而使他们面临更高的药物相互作用和不必要的出血风险。在支架植入术的早期，出血最初被认为是一种麻烦，但最近人们认识到，出血会增加冠心病患者的死亡率。使用BMS可能增加的重复手术风险与长期使用双重抗血小板治疗可能增加的出血风险之间的平衡需要进一步研究。双重抗血小板（DAPT）研究将> 20，000名患者随机分配至12个月或30个月的双重抗血小板药物。这项试验的独特之处在于它将研究所有参与者，没有年龄上限，并将收集出血，药物中断和不良心脏事件的数据。我们打算研究DAPT研究老年人亚组，并比较双重抗血小板治疗和支架类型的有效性和风险差异。还将分析3年和4年随访时来自州授权登记研究（收集马萨诸塞州所有支架植入术的信息）的心脏病发作、卒中、重复手术和出血率数据。从该项目中获得的信息将为老年患者的医生提供关于冠心病支架植入术和药物治疗的指导，特别是关于抗血小板药物的类型和持续时间。 公共卫生相关性：冠心病治疗的一个重要方面需要在心脏动脉中放置药物涂层和未涂层支架以打开阻塞。防止支架凝血所需的药物也会增加出血风险，根据目前的可用数据，这些支架和药物在老年人中的安全性并不完全清楚。我们项目的目标是研究这些药物和支架在老年人中的安全性和有效性，作为这些血栓预防药物的20，000例患者随机试验的一部分，以及管理马萨诸塞州所有冠状动脉支架植入术信息的全州注册表。

DESCRIPTION (provided by applicant): Coronary heart disease is the leading cause of death in the United States. The elderly, those older than 65 years of age, are more likely to have coronary disease and this problem will become even more pervasive as the population ages. Stenting of coronary blockages has become a conventional technique in both the emergency setting of a heart attack as well as more routine therapy to reduce chest pain. In general, there are two types of coronary stents: drug-coated (or drug-eluting stents, DES) and non-drug- coated (or bare metal stents, BMS). Placement of either type of stent requires treatment with clot- preventing medications such as aspirin and clopidogrel or prasugrel to keep them open. The latter two are newer types of medications that work in conjunction with aspirin to reduce the function of cells that help form blood clots in the body (platelets), thereby preventing clot formation on stents (stent thrombosis). Currently, the American College of Cardiology / American Heart Association recommend continuation of these medications for at least one year following DES and for at least one month following BMS placement. Initial studies comparing DES to BMS showed that by reducing scar formation around stents, DES are less likely to close up and require repeat procedures. Recruitment of elderly in these studies was limited and subjects were generally healthier when compared to the community-dwelling elderly. Despite lack of such information, the elderly routinely receive DES during cardiac procedures, requiring the obligatory one-year of anti-platelet drugs. On average, the elderly are more likely to be taking multiple medications, have a lower body weight, and have worse kidney function than the relatively healthier population in randomized trials, thereby putting them at higher risk of drug-drug interactions and unwanted bleeding. Bleeding, which was originally considered just a nuisance in the early days of stenting, has more recently been recognized to increase mortality in patients with coronary heart disease. The balance of possible increased risk of repeat procedures with the use of BMS and potentially increased risk of bleeding with long-term use of dual antiplatelet therapy needs further investigation. The Dual Antiplatelet (DAPT) Study will randomize > 20,000 patients to either 12 versus 30 months of dual antiplatelet drugs. This trial is unique in that it will study all-comers, there is no upper age limit, and will collect data on bleeding, interruptions of medications, and adverse cardiac events. We intend to study the DAPT Study elderly subset and compare differences in effectiveness and risk of dual antiplatelet therapy and stent types. Data on the rate of heart attacks, stroke, repeat procedures, and bleeding from a state-mandated registry which collects information on all stenting procedures in Massachusetts will also be analyzed for 3 and 4 year follow-up. Information obtained from this project will provide guidance to physicians caring for elderly patients toward stenting and medical treatment of coronary heart disease, particularly in regards to type and duration of antiplatelet drugs. PUBLIC HEALTH RELEVANCE: An important aspect of the management of coronary heart disease entails placement of drug coated and uncoated stents in the heart arteries to open up blockages. Medications required to prevent the stents from clotting can also increase the risk of bleeding and safety of these stents and medication in the elderly is not entirely clear based on current available data. The goal of our project is to study the safety and efficacy of these medications and stents in the elderly as part of a 20,000 patient randomized trial of these clot prevention medications and a statewide registry that manages information on all coronary stenting procedures done in Massachusetts.