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

患有阿尔茨海默病和相关痴呆症的老年人停用阿司匹林的健康结果

• 批准号: 10662129
• 负责人: Carolyn Timberlake Thorpe
• 金额: $ 64.96万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662129
• 关键词: Accident and Emergency department; Address; Admission activity; Adult; Age; Alzheimer' s disease related dementia; Anti-Inflammatory Agents; Aspirin; Atherosclerosis; Attention; Bar Codes; Behavioral; Benefits and Risks; Cardiovascular system; Caregivers; Clinical; Cognition; Data; Data Set; Decision Making; Dementia; Demographic Factors; Dependence; Dose; Drug Interactions; Elderly; Electronic Health Record; Emergency department visit; Epidemiologic Methods; Event; Exclusion; Family; Future; Goals; Guidelines; Health; Health Status; Health system; Healthcare; Hemorrhage; Hospitalization; Impaired cognition; Life Expectancy; Link; Medicare; Methods; Modeling; National Institute on Aging; Non-Prescription Drugs; Nursing Homes; Observational Study; Outcome; Palliative Care; Patient-Focused Outcomes; Patients; Pattern; Pharmaceutical Preparations; Pharmacoepidemiology; Policies; Polypharmacy; Population; Positioning Attribute; Practice Guidelines; Predictive Factor; Prevention; Prevention trial; Preventive; Primary Prevention; Probability; Prognosis; Provider; Quality of Care; Randomized; Recommendation; Records; Regimen; Research; Research Priority; Retrospective cohort study; Risk; Secondary Prevention; Selection Bias; Signal Transduction; Structural Models; Time; Translating; Uncertainty; United States Department of Veterans Affairs; Variant; World Health; adverse drug reaction; atherosclerosis risk; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular risk factor; care providers; cognitive function; cohort; design; disability; discontinuation trial; empowerment; experience; frailty; functional decline; health assessment; human old age (65+); improved; medication administration; mortality; patient oriented; prevent; psychological symptom; randomized trial; socioenvironmental factor; thrombotic; treatment duration; treatment guidelines

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.

项目摘要/摘要 通过降低收益和增加风险的药物来降低多药治疗是优先的 老年人（OAS）患有阿尔茨海默氏病和相关痴呆症（ADRD）。低剂量阿司匹林用于原发性或 已经提出了对动脉粥样硬化心血管疾病（ASCVD）的次要预防 中断，现实世界中的数据有限，表明处方和停药的差异很大。 指南建议针对OAS中的阿司匹林预防阿司匹林，同时支持其用于次要的使用 预防;但是，使用ADRD对OAS的适用性值得怀疑。与OA的预期寿命降低 ADRD可能会转化为较低的长期ASCVD益处，而药物相互作用的潜力增加可能 增加短期出血风险。另一方面，ADRD的OA之间的ASCVD风险更高 他们在停产后几周内在其他人群中观察到的ASCVD事件的风险更大 阿司匹林以及阿司匹林的抗炎和抗栓性作用也可以预防进一步 认知或功能下降的进展。用ADRD排除OAS之外的OA 阿司匹林和关于阿司匹林使用（一种非处方药）的观察数据的有限可用性使患者， 提供者和看护人几乎没有证据表明福利和危害，以指导有关知情的决定 阿司匹林中止。我们的长期目标是改善OA的决策，护理质量和成果 通过ADRD，通过改进有关药物优化的证据和治疗指南作为ADRD 进展。拟议的回顾性队列研究将在每日阿司匹林上使用记录独特地使用 可用于全国退伍军人事务（VA）护士之家（NH）的居民，与ADRD相关联 最低数据集（MDS）评估，电子健康记录以及VA和Medicare使用数据 2016-2023。具体目的是（1）确定预测阿司匹林的临床和社会环境因素 NH入院后用ADRD中断OAS，按ASCVD状态分层； （2）检查 停止在ASCVD事件，重大出血，急诊室/住院以及 死亡率，按ASCVD状态分层； （3）检查中断阿司匹林对认知功能的影响， 功能依赖性以及痴呆症的行为/心理症状。集中我们的目标 强大的，临床和与政策相关的证据，我们将使用药物ePidemiologic方法来减少 选择偏见和混杂。 AIM 2是一项采用协变量平衡方法的普遍新用户研究 竞争风险模型，以及补充分析，以解决时变的阿司匹林暴露和 混淆者。 AIM 3将评估时变的暴露和使用反向概率加权的混淆 边缘结构模型。这项研究将告知未来的实践指南，以解决阿司匹林是否可以安全 与ADRD中断，并授权患者，看护人和提供者做出明智的决定。