Effectiveness and Safety of Transcatheter Left Atrial Appendage Occlusion vs. Anticoagulation in Older Adults with Atrial Fibrillation and Alzheimer's Disease and Related dementias

项目摘要 非瓣膜性心房颤动(房颤)在老年人中非常普遍，并与增加5倍的风险有关 心脏栓塞性中风。口服抗凝剂(OAC)可以将这种风险降低约70%，但近50%的老年人 患者没有抗凝，阿尔茨海默病和相关痴呆(ADRD)是 主要列举的原因，归因于较高的跌倒风险、用药失误和依从性差。既然广袤无边 房颤时血栓形成多发生在左心耳、经导管左心耳 自2015年以来，闭塞术(LAAO)已在美国获得批准，作为一种一次性的程序性替代治疗方法 房颤患者OAC并发症高危人群的卒中预防。经导管对LAAO的摄取 以每年2到3倍的速度增长，显然正在改变房颤患者OAC的处方模式 病人。然而，我们的试点数据显示，痴呆症患者(PLWD)患痴呆症的可能性显著降低 在需要时接受经导管LAAO治疗。一个可能的障碍是PLWD和虚弱的老年人 在导致经导管LAAO批准的随机对照试验(RCT)中，该研究的代表性很低。 此外，PLWD中普遍存在的几个高危特征，包括虚弱、痴呆症严重程度、跌倒风险和 晚期肾脏疾病是经导管LAAO手术相关并发症和 OAC的出血风险，使处方决策复杂化。因此，迫切需要进行调查。 净临床收益，权衡卒中预防与大出血和手术的益处 并发症，比较经导管LAAO和特定OAC在PLWDS中的应用。我们的目标是建立一个 3个大型国家医疗保健利用数据库(Medicare、IBM MarketScan、 与电子健康记录(EHR)相关联的2015年至2025年的Optus索赔数据(涵盖约1500万人的生命)。 我们将评估经导管LAAO与特异性OAC在伴有房颤的PLWDS中的治疗结果。 通过虚弱、痴呆症严重程度、跌倒风险、晚期肾脏疾病和 患者报告的因素和家庭因素。我们还将确定以下各项的利用率趋势、预测因素和障碍 经导管LAAO和OAC在PLWD中的应用，使用由The 申请者团队，并被美国食品和药物管理局采用，用于预期的药物安全监测。 我们的中心假设是，与经导管LAAO相比，经导管LAAO具有良好的长期净临床益处 OAC在PLWD中的应用及其相对益处因特定的可识别的临床因素而异。这项建议将产生：1) 直接的风险效益数据，为使用经导管LAAO和特定的OAC预防中风提供信息 2)一个新的和可推广的前瞻性监测计划，将有效性和 具有详细治疗效果的PLWD中新上市医疗器械的安全性与药物疗法的比较 异质性评价。

Project Summary Non-valvular atrial fibrillation (AF) is highly prevalent in older adults and associated with a 5-fold increased risk of cardioembolic stroke. Oral anticoagulants (OACs) can reduce this risk by ~70%, but nearly 50% of such older patients are not anticoagulated, with Alzheimer’s disease and related dementias (ADRD) being among the leading cited reasons, attributed to a higher risk of falls, medication errors, and poor adherence. Since the vast majority of thrombus formation in AF occurs in the left atrial appendage, transcatheter left atrial appendage occlusion (LAAO) has been approved in the US since 2015 as a one-time procedural alternative treatment for stroke prevention in AF patients with high risks of complications from OACs. The uptake of transcatheter LAAO has been growing at a rate of 2 to 3-fold yearly, and it is clearly changing the prescribing pattern of OACs in AF patients. However, our pilot data showed persons living with dementia (PLWDs) are significantly less likely to receive transcatheter LAAO when it is indicated. One likely barrier is that PLWDs and frail older adults were much under-represented in the randomized controlled trials (RCTs) which led to transcatheter LAAO approval. Also, several high-risk characteristics prevalent in PLWDs, including frailty, dementia severity, fall risks, and advanced kidney disease, are risk factors for both the transcatheter LAAO procedure-related complications and bleeding risks from OACs, complicating the prescribing decisions. Thus, there is an urgent need to investigate the net clinical benefit, weighing the benefits of stroke prevention against the major bleeding and procedure complications, comparing transcatheter LAAO with specific OACs in PLWDs. Our objective is to establish a prospective monitoring program in 3 large national healthcare utilization databases (Medicare, IBM Marketscan, and Optum claims data, covering ~15 million lives) from 2015-2025, linked to electronic health records (EHR). We will evaluate treatment outcomes of transcatheter LAAO vs. specific OACs in PLWDs with AF with detailed treatment effect heterogeneity evaluation by frailty, dementia severity, fall risks, advanced kidney disease, and patient-reported and family factors. We will also determine the utilization trends, predictors, and barriers of transcatheter LAAO and OACs in PLWDs, using a novel signal detection tool, TreeScan, developed by the applicant team and adopted by the US Food and Drug Administration for prospective drug safety monitoring. Our central hypothesis is that transcatheter LAAO has a favorable long-term net clinical benefit compared with OACs in PLWDs and the relative benefits vary by specific identifiable clinical factors. This proposal will yield: 1) direct benefit-to-risk data to inform the use of transcatheter LAAO and specific OACs for stroke prevention in PLWDs with AF; 2) a novel and generalizable prospective monitoring program that compares effectiveness and safety of newly marketed medical devices vs. pharmacotherapies in PLWDs with detailed treatment effect heterogeneity evaluation.