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: 10221577
• 负责人: Andrew T Chan
• 金额: $ 850.9万
• 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/10221577
• 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/总结 在美国，低剂量阿司匹林 (LDA) 是使用最广泛的药物之一，因为它在治疗疾病方面发挥了既定的作用。 心血管疾病（CVD）的二级预防。近年来，一些专家机构，包括 美国预防服务工作组 (USPSTF) 建议在初级预防中常规使用 LDA 基于先前随机化的大量数据预防 CVD 和结直肠癌 (CRC) 对照试验（RCT）主要在年轻人中进行。但对于70岁以上的成年人来说 USPSTF 认为当前支持净效益的证据不足。此外，还需要延长 鉴于社会和人口的不断增长，健康的独立生活、无痴呆和严重残疾至关重要。 人口日益老龄化带来的经济成本。为了解决这些知识差距，NIA/NCI- 赞助的 ASPirin 减少老年人事件 (ASPREE) 研究是一项突破性的研究 随机对照试验从 2010 年起招募了 19,114 名最初健康的 70 岁以上（美国少数族裔为 65 岁以上）老年人 2014 年，美国和澳大利亚研究是否开始 5 年每天服用低剂量阿司匹林（LDA；100 毫克/天）可延长老年人的健康寿命。 2017年6月，随机治疗阶段 ASPREE 在中位治疗 4.6 年后被暂停，因为 LDA 对 主要结局为无残疾生存期（DFS）。对于次要结果，LDA 出乎意料地与 由于死亡过多导致全因死亡风险增加（HR 1.14；95% CI，1.01,1.28） 癌症，尽管癌症发病率没有增加。此外，LDA 显示出事件发生率降低的趋势 身体整体残疾。这些具有挑战性的初步发现要求继续研究和跟踪 ASPREE 队列通过此 U19 提案。我们的总体目标是生成有关 阿司匹林在老年人中的作用，在老年人群中，阿司匹林对慢性病一级预防的风险/益处 疾病已得到充分研究。我们的首要假设是 ASPREE 的后续行动 该队列将展示 LDA 对癌症、痴呆和残疾的长期“传统”益处。我们进一步 假设在随访期间收集的广泛基因组、生化和成像相关性将提供 对 LDA 对这些终点的影响的独特生物学见解可能会带来机械启发 生物标志物为慢性病预防提供更“精确”的预防方法。因此，我们建议 建立 ASPREE-XT，在未来 5 年内扩大对 ASPREE 参与者的跟踪，以追求三个目标 重点关注癌症、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，促进协同与协作。这支 U19 球队由一支多学科的国际团队共同领导 领先研究人员的合作，将为定义 LDA 的长期功效提供前所未有的机会 指导临床建议并提供对领先药物的生物学基础的基本见解 老年人痴呆、残疾和死亡的原因。