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: 10672458
• 负责人: JOSHUA K LIN
• 金额: $ 70.97万
• 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/10672458
• 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; Marketing; Medical Device; Medicare; Medication Errors; Methodology; Modality; Monitor; Oral; 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 trend; Treatment outcome; United States Food and Drug Administration; Warfarin; 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.

项目概要 非瓣膜性心房颤动 (AF) 在老年人中非常普遍，且风险增加 5 倍 口服抗凝剂 (OAC) 可以将这种风险降低约 70%，但此类老年人的风险却降低了近 50%。 患者未接受抗凝治疗，阿尔茨海默病和相关痴呆症 (ADRD) 属于其中之一 领导者列举的原因，归因于跌倒风险较高、用药错误和依从性差。 AF 的血栓形成大部分发生在左心耳，经导管左心耳 封堵术 (LAAO) 自 2015 年起在美国获得批准，作为一种一次性手术替代治疗方法 发生 OAC 并发症高风险的 AF 患者的卒中预防 经导管 LAAO 的摄取。 每年以 2 至 3 倍的速度增长，这明显改变了 AF 中 OAC 的处方模式 然而，我们的试点数据显示，痴呆症患者 (PLWD) 的可能性明显较低。 在有指征时接受经导管 LAAO 可能的障碍之一是 PLWD 和体弱的老年人。 导致经导管 LAAO 批准的随机对照试验 (RCT) 中的代表性严重不足。 此外，PLWD 中普遍存在一些高风险特征，包括虚弱、痴呆严重程度、跌倒风险和 晚期肾脏疾病是经导管 LAAO 手术相关并发症和的危险因素 OAC 的出血风险使处方决策变得复杂，因此迫切需要进行调查。 净临床效益，权衡预防中风与大出血和手术的效益 并发症，比较经导管 LAAO 与 PLWD 中的特定 OAC。 3 个大型国家医疗保健利用数据库（Medicare、IBM Marketscan、 Optum 索赔数据涵盖 2015 年至 2025 年约 1500 万人的生命，并与电子健康记录 (EHR) 相关联。 我们将评估经导管 LAAO 与特定 OAC 在患有 AF 的 PLWD 中的治疗结果，并详细说明 根据虚弱、痴呆严重程度、跌倒风险、晚期肾病和 我们还将确定患者报告和家庭因素的使用趋势、预测因素和障碍。 使用由 PLWD 开发的新型信号检测工具 TreeScan 进行经导管 LAAO 和 OAC 申请人团队并被美国食品和药物管理局采纳用于前瞻性药物安全监测。 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效益 PLWD 中的 OAC 和相关益处因具体可识别的临床因素而异。该提案将产生：1)。 直接效益与风险数据，为经导管 LAAO 和特定 OAC 的使用提供信息，以预防中风 患有 AF 的 PLWD；2) 一种新颖且可推广的前瞻性监测计划，用于比较有效性和 新上市医疗器械与药物治疗在 PLWD 中的安全性及详细治疗效果 异质性评价。