Health Outcomes of Discontinuing Aspirin in Older Adults with Alzheimer's Disease and Related Dementias

项目总结/摘要 通过停用获益减少、风险增加的药物来减少多药治疗是 老年人（OAs）患有阿尔茨海默病和相关痴呆症（ADRD）。低剂量阿司匹林用于原发性或 动脉粥样硬化性心血管疾病（ASCVD）的二级预防已被提出作为 停药，有限的真实世界数据表明处方和停药的差异很大。 指南建议不要将阿司匹林用于OAs的一级预防，同时支持将其用于二级预防。 预防;然而，对患有ADRD的OAs的适用性值得怀疑。OAs的预期寿命缩短， ADRD可能转化为较低的长期ASCVD获益，而药物相互作用可能增加 增加短期出血风险。另一方面，患有ADRD的OAs中ASCVD风险较高， 在停药后数周内，先前在其他人群中观察到的ASCVD事件风险更高 阿司匹林的抗炎和抗血栓形成作用也可以防止进一步的 认知或功能下降的进展。从随机试验中排除患有ADRD的OAs， 阿司匹林和阿司匹林使用（非处方药）的观察数据有限， 提供者和护理人员几乎没有关于益处和危害的证据来指导明智的决策， 阿司匹林停药我们的长期目标是改善OAs的决策、护理质量和结果 通过改善关于药物优化为ADRD的证据和治疗指南， 进步。拟议的回顾性队列研究将使用每日阿司匹林使用记录， 适用于患有ADRD的退伍军人事务部（VA）疗养院（NH）居民的国家队列，与 最小数据集（MDS）评估、电子健康记录以及VA和Medicare利用率数据， 2016-2023.具体目标是（1）确定预测阿司匹林的临床和社会环境因素 NH入院后OAs伴ADRD的停药，按ASCVD状态分层;（2）检查 发生ASCVD事件、大出血、急诊/住院时停用阿司匹林，以及 死亡率，按ASCVD状态分层;和（3）检查停用阿司匹林对认知功能的影响， 功能依赖和痴呆的行为/心理症状。把我们的目标集中在 强有力的，临床和政策相关的证据，我们将使用药物流行病学方法，以减少 选择偏倚和混杂。目标2是一项普遍的新用户研究，采用协变量平衡方法， 竞争风险模型，补充分析以解决随时间变化的阿司匹林暴露， 混杂因素。目标3将使用逆概率加权法评估随时间变化的暴露和混杂因素 边际结构模型这项研究将为未来的实践指南提供信息，以解决阿司匹林是否可以安全地 在患有ADRD的OAs中停用，并使患者、护理人员和提供者能够做出明智的决定。

PROJECT SUMMARY/ABSTRACT Reducing polypharmacy by discontinuing medications with reduced benefits and increased risks is a priority in older adults (OAs) with Alzheimer’s Disease and Related Dementias (ADRD). Low-dose aspirin for primary or secondary prevention of atherosclerotic cardiovascular disease (ASCVD) has been proposed as a target for discontinuation, with limited real-world data suggesting high variation in prescribing and discontinuation. Guidelines recommend against aspirin for primary prevention in OAs, while supporting its use for secondary prevention; however, applicability to OAs with ADRD is questionable. Reduced life expectancy for OAs with ADRD may translate into lower long-term ASCVD benefits, while increased potential for drug interactions may increase short-term bleeding risk. On the other hand, higher ASCVD risk among OAs with ADRD may position them for greater risk of ASCVD events previously observed in other populations in weeks after discontinuing aspirin, and the anti-inflammatory and anti-thrombotic effects of aspirin could also protect against further progression of cognitive or functional decline. The exclusion of OAs with ADRD from randomized trials of aspirin and limited availability of observational data on aspirin use (a non-prescription drug) leaves patients, providers, and caregivers with little evidence about benefits and harms to guide informed decisions about aspirin discontinuation. Our long-term goal is to improve decision-making, care quality, and outcomes for OAs with ADRD, through improved evidence and treatment guidelines about medications optimization as ADRD progresses. The proposed retrospective cohort study will use records on daily aspirin use uniquely available for a national cohort of Veterans Affairs (VA) nursing home (NH) residents with ADRD, linked to Minimum Data Set (MDS) assessments, electronic health records, and VA and Medicare utilization data over 2016-2023. Specific aims are to (1) Identify clinical and socio-environmental factors predicting aspirin discontinuation in OAs with ADRD after NH admission, stratified by ASCVD status; (2) Examine effects of discontinuing aspirin on ASCVD events, major bleeding, emergency department/hospital admissions, and mortality, stratified by ASCVD status; and (3) Examine effects of discontinuing aspirin on cognitive function, functional dependence, and behavioral/psychological symptoms of dementia. To focus our aims on generating robust, clinically- and policy-relevant evidence, we will use pharmacoepidemiologic methods to reduce selection bias and confounding. Aim 2 is a prevalent new-user study applying covariate balancing methods and competing risk models, with supplementary analyses to address time-varying aspirin exposure and confounders. Aim 3 will assess time-varying exposures and confounding using inverse-probability-weighted marginal structural models. This study will inform future practice guidelines to address if aspirin can be safely discontinued in OAs with ADRD and empower patients, caregivers, and providers to make informed decisions.