ASPirin in Reducing Events in the Elderly - eXTension

阿司匹林在减少老年人事件中的作用 - eXTension

• 批准号: 10428600
• 负责人: Andrew T Chan
• 金额: $ 796.99万
• 依托单位: HENNEPIN HEALTHCARE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10428600
• 关键词: Address; Adult; Advisory Committees; Alzheimer' s Disease; Aspirin; Australia; Benefits and Risks; Biochemical; Biological; Biological Markers; Biometry; Blood; Brain imaging; Cancer Etiology; Cardiovascular Diseases; Cessation of life; Chronic Disease; Clinical; Cognitive; Collaborations; Collection; Colorectal Cancer; Complex; Data; Dementia; Disease; Dose; Elderly; Enrollment; Event; Genomics; Goals; Health; Image; Incidence; Individual; Inflammation; Infrastructure; International; Knowledge; Lead; Leadership; Life; Longevity; Longterm Follow-up; Malignant Neoplasms; Measures; Minority; Modeling; Outcome; Participant; Persons; Pharmaceutical Preparations; Phase; Physical Function; Population; Precision Medicine Initiative; Prevention approach; Preventive service; Primary Prevention; Randomized; Randomized Controlled Trials; Recommendation; Research; Research Personnel; Resistance; Risk; Role; Secondary Prevention; United States National Institutes of Health; Urine; adjudicate; aged; aging population; base; cancer prevention; cardiovascular disorder prevention; cognitive function; cohort; comorbidity; cost effective; data management; disability; disorder prevention; economic cost; experience; follow-up; frailty; individualized prevention; insight; mortality; multidisciplinary; personalized approach; physically handicapped; primary endpoint; primary outcome; randomized placebo controlled trial; recruit; resilience; retinal imaging; secondary outcome; social; synergism; trend; tumor; young adult

OVERALL RESEARCH PLAN - ABSTRACT / SUMMARY In the U.S., low dose aspirin (LDA) is one of the most widely used medications given its established role in the secondary prevention of cardiovascular disease (CVD). In recent years, several expert bodies, including the U.S. Preventive Services Task Force (USPSTF), have recommended the routine use of LDA for the primary prevention of both CVD and colorectal cancer (CRC) based on substantial data from prior randomized controlled trials (RCTs) primarily conducted among younger adults. However, for adults aged 70+, the USPSTF deemed current evidence supporting a net benefit insufficient. Furthermore, the need to prolong healthy independent life, free of dementia and significant disability, is critical given the rising social and economic costs of the increasingly aging population. To address these knowledge gaps, the NIA/NCI- sponsored ASPirin in Reducing Events in the Elderly (ASPREE) study was developed as a ground-breaking RCT that recruited 19,114 initially healthy older individuals aged 70+ years (65+ for U.S. minorities) from 2010- 2014 in the U.S. and Australia to examine whether initiation of 5 years of low-dose daily aspirin (LDA; 100 mg/day) prolonged the healthy lifespan of older adults. In June 2017, the randomized treatment phase of ASPREE was suspended after a median of 4.6 years of treatment due to lack of an effect of LDA on the primary outcome of disability-free survival (DFS). For secondary outcomes, LDA unexpectedly was associated with an increased risk of all-cause mortality (HR 1.14; 95% CI, 1.01,1.28) driven by an excess of deaths due to cancer, despite no increase in incident cancer. Furthermore, LDA showed a trend toward lower incident physical disability overall. These provocative initial findings obligate continued study and follow-up of the ASPREE cohort through this U19 proposal. Our overall goal is to generate fundamental knowledge about the role of aspirin in older adults, a population in which aspirin's risk/benefit for primary prevention of chronic disease has been understudied. Our overarching hypothesis is that extended follow-up of the ASPREE cohort will demonstrate a long-term `legacy' benefit of LDA on cancer, dementia and disability. We further hypothesize that extensive genomic, biochemical, and imaging correlates collected during follow-up will offer unique biological insight into LDA's effects on these endpoints that may lead to mechanistically-inspired biomarkers for more `precision' prevention approaches to chronic disease prevention. Thus, we propose to establish ASPREE-XT to extend follow-up in ASPREE participants over the next 5 years to pursue three Projects focused on cancer, dementia (including Alzheimer's), and physical disability that will be supported by 6 Cores, facilitating synergy and collaboration. Together, this U19, led by a multidisciplinary, international team of leading investigators, will provide an unprecedented opportunity to define the long-term efficacy of LDA to guide clinical recommendations and offer fundamental insights into the biological underpinnings of the leading causes of dementia, disability and death among older adults.

总体研究计划 - 摘要 /摘要 在美国，低剂量阿司匹林（LDA）是使用最广泛的药物之一 心血管疾病（CVD）的次要预防。近年来，几个专家机构，包括 美国预防服务工作队（USPSTF）建议将LDA常规使用 基于先前随机的大量数据，预防CVD和结直肠癌（CRC）（CRC） 对照试验（RCT）主要在年轻人中进行。但是，对于70岁以上的成年人 USPSTF认为当前的证据支持净福利不足。此外，需要延长 鉴于社会的上升和 越来越老化的人口的经济成本。为了解决这些知识差距，NIA/NCI- 在减少老年人（ASPREE）研究中的赞助阿司匹林中，作为一项突破性的研究 从2010年开始招募了1914名年龄在70岁以上（65岁以上）的最初健康的老年人，从2010年开始招募RCT。 2014年在美国和澳大利亚，检查是否需要5年的低剂量每日阿司匹林（LDA； 100） mg/day）延长了老年人的健康寿命。 2017年6月，随机治疗阶段 由于缺乏LDA对The The The The The The的影响 无残疾生存期（DFS）的主要结果。对于次要结果，LDA意外相关 由于因因死亡人数过多而增加了全因死亡率的风险（HR 1.14; 95％CI，1.01,1.28） 癌症，尽管事件癌症没有增加。此外，LDA显示出较低事件的趋势 身体残疾总体上。这些挑衅性的初始发现强迫继续研究和随访 通过此U19提案的Aspree队列。我们的总体目标是产生有关 阿司匹林在老年人中的作用，阿司匹林的风险/受益于主要预防慢性的人群 疾病已经被研究了。我们的总体假设是Aspree的扩展后续行动 队列将证明LDA对癌症，痴呆和残疾的长期“遗产”益处。我们进一步 假设在随访期间收集的广泛的基因组，生化和成像相关 对LDA对这些端点的影响的独特生物学见解，这些终点可能导致机械启发 生物标志物，用于预防慢性疾病的更多“精度”预防方法。因此，我们建议 建立Aspree-XT，以扩展未来5年的ASPREE参与者的后续行动以追求三个 专注于癌症，痴呆症（包括阿尔茨海默氏症）和身体残疾的项目将由 6个核心，促进协同和协作。由多学科的国际团队领导的U19一起 领先的调查人员将提供一个前所未有的机会，以定义LDA的长期功效 指导临床建议，并提供有关领先的生物基础的基本见解 老年人痴呆，残疾和死亡的原因。