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 心脏束缚中风。口服抗凝剂（OAC）可以将这种风险降低约70％，但几乎50％ 患者没有抗凝，患有阿尔茨海默氏病和相关痴呆症（ADRD） 主要的引用原因，归因于跌倒，药物错误和依从性较差的较高风险。由于病毒 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，美国已在美国批准了阻塞（LAAO）作为一次性的程序替代方法 OAC并发症高风险的AF患者的中风预防。经导管LAAO的吸收 每年以2至3倍的速度增长，它显然正在改变AF中OAC的处方模式 患者。但是，我们显示患有痴呆症（PLWD）的人的试点数据明显较小 指示时接收经导管LAAO。一个可能的障碍是，PLWD和脆弱的老年人是 在随机对照试验（RCT）中的代表性不足，这导致了经导管LAAO的批准。 此外，在PLWD中普遍存在的几种高风险特征，包括脆弱，痴呆严重程度，跌倒风险和 晚期肾脏疾病是经导管LAAO程序相关并发症和 OAC的出血风险，使开处方的决定变得复杂。那迫切需要调查 净临床利益，权衡预防中风的好处与主要出血和程序 并发症，将经导管LAAO与PLWD中的特定OAC进行比较。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中的预期监测计划（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OAC的治疗结果 治疗效应脆弱，痴呆严重程度，跌倒风险，晚期肾脏疾病和 患者报告和家庭因素。我们还将确定利用率趋势，预测因素和障碍 经导管LAAO和PLWD中的OAC，使用新型的信号检测工具，TreeCan，由Tookcan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，与经导管LAAO相比具有有利的长期净临床益处 PLWD中的OAC和相对益处因特定可识别的临床因素而异。该提议将产生：1） 直接利益风险数据，以告知经导管LAAO和特定OAC的使用，以预防中风 带有AF的PLWD； 2）一个新颖且可概括的前瞻性监测计划，可比较有效性和 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。