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

经导管左心耳封堵术与抗凝治疗对患有心房颤动、阿尔茨海默病及相关痴呆症的老年人的有效性和安全性

• 批准号: 10443345
• 负责人: JOSHUA K LIN
• 金额: $ 71.96万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10443345
• 关键词: Address; Adherence; Adopted; Affect; Algorithms; Alzheimer' s disease related dementia; Anticoagulants; Anticoagulation; Atrial Fibrillation; Calibration; Characteristics; Clinical; Clinical Data; Data; Databases; Dementia; Detection; Devices; Effectiveness; Elderly; Electronic Health Record; Evaluation; Family; Frail Elderly; Goals; Hemorrhage; Heterogeneity; Kidney Diseases; Knowledge; Left; Link; Machine Learning; Medical Device; Medicare; Medication Errors; Methodology; Modality; Monitor; Oral; Outcome; Patient Preferences; Patients; Pattern; Persons; Pharmacoepidemiology; Pharmacotherapy; Phenotype; Predictive Value; Prevention strategy; Probability; Procedures; Proxy; Public Health; Randomized Controlled Trials; Reporting; Research; Risk; Risk Factors; Safety; Selection for Treatments; Severities; Signal Transduction; Stroke; Stroke prevention; Subgroup; Testing; Thrombus; Time; Time trend; Treatment outcome; United States Food and Drug Administration; Warfarin; Weight; alternative treatment; auricular appendage; cohort; comparative effectiveness; comparative safety; compare effectiveness; data mining; fall risk; frailty; health care service utilization; high dimensionality; high risk; human old age (65+); medication safety; multidimensional data; novel; older patient; phenotyping algorithm; programs; prospective; routine care; safety outcomes; tool; treatment effect; trend; uptake; vaccine safety

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.

项目摘要 非浮力心房颤动（AF）在老年人中非常普遍，风险增加了5倍 心脏骨骼中风的口服抗凝剂（OAC）可以降低〜70％ 患者没有抗凝，患有阿尔茨海默氏病和相关痴呆症（ADRD） 引用的原因是，自大量的跌倒，药物错误和依从性较差的原因 AF中大部分的血栓形成发生在左心房附属物中，经导管左心房附属物 自2015年以来，闭塞（LAAO）已在美国批准，高达一定程度高达一次性的程序替代治疗 OAC的汇编风险的AF患者的中风预防。 每年以2至3倍的速度增长，它显然正在改变AF AF AF中OAC的处方者模式 但是，我们的飞行员数据显示，患有痴呆症的人（PLWD）可能会显着降低 指示时接收经导管LAAO。 在随机对照试验（RCT）中，导致经导管LAAO批准的情况不足。 此外，在PLWD中普遍存在的几种高风险特征，包括脆弱，痴呆症的严重程度，跌倒风险以及 晚期肾脏疾病是经导管LAAO程序相关的复杂性和 OAC的出血风险，使开处方的决定变得复杂。 净临床益处，重量预防中风的益处针对主要出血和程序 并发症，将经导管LAAO与PLWD中的特定OAC进行比较。 3个大型国家医疗保健利用数据库中的潜在监测计划（Medicare，IBM MarketScan， 从2015 - 2025年开始，与电子健康记录（EHR）相关的Optum索赔数据，涵盖了约1500万寿命）。 我们将评估带有详细的AF的经导管LAAO与特定的OAC的治疗CORTOM 治疗效果脆弱，痴呆症的严重程度，跌倒风险，晚期肾脏疾病的异质性评估 患者报告和家庭因素。 经导管LAAO和PLWD中的OACS，使用新型信号检测工具，Treescan，由Thee开发 申请人团队，并由美国食品药品监督管理局（Adiment Administry）采用前瞻性药物安全监测。 我们的中心假设是，与与之相比，经导管老挝具有有利的长期净临床益处。 PLWD中的OAC和相对益处因特定的可识别临床因素而异。 直接利益到风险数据，以告知经导管LAAO和特定OAC的使用，以预防中风 带有AF的PLWD 新销售的医疗设备与PLWD中具有详细治疗效果的药物治疗的安全性 异质性评估。