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 非瓣膜性房颤（AF）在老年人中非常普遍，并且与5倍的风险增加相关 心源性中风口服抗凝剂（OACs）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）是其中之一。 主要引用的原因，归因于较高的福尔斯风险、用药错误和依从性差。由于绝 AF中的大多数血栓形成发生在左心耳、经导管左心耳 自2015年以来，LAAO已在美国获批作为一次性手术替代治疗，用于 OAC并发症风险高的AF患者的卒中预防。经导管LAAO的摄取 以每年2 - 3倍的速度增长，这显然正在改变AF患者中OAC的处方模式 患者然而，我们的试点数据显示，痴呆症患者（PLWD） 在有指征时接受经导管LAAO。一个可能的障碍是PLWD和体弱的老年人 在导致经导管LAAO批准的随机对照试验（RCT）中代表性不足。 此外，PLWD中普遍存在的几个高风险特征，包括虚弱，痴呆严重程度，跌倒风险， 晚期肾脏疾病是经导管LAAO手术相关并发症的风险因素， OAC的出血风险，使处方决策复杂化。因此，迫切需要调查 净临床获益，权衡卒中预防与大出血和手术的获益 并发症，比较PLWD中的经导管LAAO与特定OAC。我们的目标是建立一个 在3个大型国家医疗保健利用数据库（Medicare，IBM Marketscan， 和Optum索赔数据，涵盖2015-2025年的约1500万人），与电子健康记录（EHR）相关联。 我们将评价PLWD伴AF患者经导管LAAO与特定OAC的治疗结局， 根据虚弱、痴呆严重程度、跌倒风险、晚期肾病和 患者报告和家庭因素。我们还将确定 PLWD中的经导管LAAO和OAC，使用由 申请人团队，并通过了美国食品和药物管理局的前瞻性药物安全性监测。 我们的中心假设是，与LAAO相比，经导管LAAO具有良好的长期净临床受益。 PLWD中的OAC和相对获益因具体可识别的临床因素而异。该提案将产生：1） 直接获益-风险数据，为经导管LAAO和特定OAC用于卒中预防提供信息， PLWD伴AF; 2）一种新的、可推广的前瞻性监测项目， 新上市医疗器械与药物治疗PLWD的安全性，详细治疗效果 非均质性评价

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.