PRagmatic EValuation of evENTs And Benefits of Lipid-lowering in oldEr Adults (PREVENTABLE)

由于人口结构的变化，迫切需要证据来指导老年人的临床护理，包括 预期寿命延长，最近老年人口翻了一番。他汀类药物减少复发性CVD事件 并预防75岁以下患者的初始事件。然而，临床研究往往排除了 75岁以上的人，由于合并症和虚弱的患病率较高，因此几乎没有证据表明 可用于指导该人群的护理。对于寿命更长的老年人来说， 损害与预防CVD事件一样引人注目，但一些证据表明他汀类药物可能 导致记忆困难或肌肉症状。关于他汀类药物的有用性， 用于75岁以上成人的原发性CVD、痴呆和残疾预防，尤其是在 患有多种慢性病、高龄或虚弱。改善认知和功能的证据 不同人种/种族和健康状况的老年人群的结局需要新的临床试验 采用可持续的方法和基础设施。我们建议可预防（PRagmatic 评价老年人降脂的事件和益处，第一个非CVD的他汀类药物试验 主要结局-无痴呆或持续残疾的存活率。使用安慰剂控制的语用 临床试验（PCT）设计跨PCORnet和VA网络，试验将在Karen博士的领导下进行 DCRI的亚历山大博士、WFSM的杰夫威廉姆森博士、DCRI的阿德里安埃尔南德斯博士和DCRI的沃尔特安布罗西乌斯博士 WFSM。该团队在设计和执行方面具有丰富的经验和良好的业绩记录 PCTs，在确定老年人认知和残疾结果方面的试验专业知识，并得到了 健全的行政基础设施，以协调这些共同责任，取得成功。总体 可预防的目标是产生关于他汀类药物在老年人中作用的知识，老年人中， 对初级预防的风险/效益进行了研究。假设是，在一个 老年人群将证明他汀类药物在减少痴呆、残疾和CV事件方面的益处。 我们进一步假设，广泛的基因组，生化和成像辅助研究将提供独特的， 对这些关键成果的理解。可预防性有以下具体目标：目标1：确定角色 中等强度他汀类药物预防痴呆和延长75岁患者的无残疾生存期 和老年人没有临床上明显的冠心病，包括那些虚弱， 功能，轻度认知障碍，多种药物和多种疾病。目的2：确定适度的作用- 强度他汀类药物预防心肌梗死/急性冠脉综合征、中风、心脏病住院 失败、血运重建或心血管相关死亡，并预防轻度认知障碍或 痴呆目的3：测试他汀类药物在老年人中的安全性和耐受性，并收集17，000份生物标本， 推进精准健康。

There is an urgent need for evidence to guide clinical care of older adults due to demographic shifts, including longer life expectancy and a recent doubling of the older adult population. Statins reduce recurrent CVD events and prevent initial events in patients younger than 75 years. However, clinical research has often excluded persons older than 75 years due to a higher prevalence of comorbidity and frailty so little to no evidence is available to guide care in this population. For older adults living longer, the promise of preventing cognitive impairment is as compelling as preventing a CVD event, but some evidence suggests statins may contribute to memory difficulty or muscle symptoms. There is equipoise regarding the usefulness of statins for primary CVD, dementia, and disability prevention in adults older than 75 years, especially in the setting of multiple chronic conditions, advanced age, or frailty. Evidence to improve cognitive and functional outcomes in older populations with diverse race/ethnicity and health status will require new clinical trial approaches with sustainable methodology and infrastructure. We propose PREVENTABLE (PRagmatic EValuation of evENTs And Benefits of Lipid-lowering in oldEr adults), the first statin trial with a non-CVD primary outcome—survival free of dementia or persisting disability. Using a placebo-controlled pragmatic clinical trial (PCT) design across PCORnet and VA network, the trial will be under the leadership of Dr. Karen Alexander at DCRI, Dr. Jeff Williamson at WFSM, Dr. Adrian Hernandez at DCRI, and Dr. Walter Ambrosius at WFSM. This team has established experience and track-record of accomplishment in the design and conduct of PCTs, trial expertise in ascertaining cognitive and disability outcomes in older adults, and is supported by a robust administrative infrastructure for coordinating these shared responsibilities for success. The overarching goal of PREVENTABLE is to generate knowledge about the role of statins in older adults, a population in which risk/benefit for primary prevention has been under studied. The hypothesis is that a large trial conducted in an older adult population will demonstrate the benefit of statins for reducing dementia, disability, and CV events. We further hypothesize that extensive genomic, biochemical and imaging ancillary studies will offer unique insights into these key outcomes. PREVENTABLE has the following specific aims: AIM 1: Determine the role of a moderate-intensity statin in preventing dementia and prolonging disability-free survival in patients 75 years and older without clinically evident coronary heart disease, including those with frailty, impaired physical function, mild cognitive impairment, polypharmacy, and multi-morbidity. AIM 2: Determine the role of moderate- intensity statin in preventing hospitalization for myocardial infarction/acute coronary syndrome, stroke, heart failure, revascularization or cardiovascular-related death, and preventing either mild cognitive impairment or dementia. AIM 3: Test the safety and tolerability of statins in older adults and collect 17,000 bio-specimens to advance precision health.