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

对老年人降脂的事件和益处进行务实评估（可预防）

基本信息

批准号：
10259715
负责人：
KAREN P ALEXANDER
金额：
$ 1848.25万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-30 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10259715
关键词：
Acute myocardial infarction Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Ancillary Study Benefits and Risks Biochemical Blood Vessels Capsicum Cardiology Cardiovascular system Caring Cessation of life Classification Clinical Clinical Research Clinical Trials Clinical Trials Design Cognitive Comparative Study Coronary heart disease Data Data Science Dementia Detection Diabetes Mellitus Effectiveness Elderly Equipoise Ethnic Origin Evaluation Event Exclusion Funding Future Genomics Geriatrics Ginkgo biloba Goals Health Health Status Healthcare Systems Heart Diseases Heart failure Heterogeneity High Prevalence Hospitalization Hyperlipidemia Image Impaired cognition Impairment Information Dissemination Infrastructure International Intervention Trial Knowledge Lead Leadership Life Expectancy Lipids Medical Memory Methodology Methods Muscle Older Population Outcome Participant Patients Pharmaceutical Preparations Physical Function Placebo Control Polypharmacy Population Population Heterogeneity Pragmatic clinical trial Precision Health Prevention Primary Prevention Race Recurrence Reporting Risk Role Safety Specimen Stroke Subgroup Symptoms United States National Institutes of Health Vascular Cognitive Impairment Veterans Health Administration acute coronary syndrome base biobank blood pressure intervention cardiovascular risk factor clinical care cognitive disability collaboratory comorbidity design disability evidence base experience frailty functional outcomes human subject improved insight medical schools mild cognitive impairment multiple chronic conditions patient population pragmatic trial preservation prevent primary outcome recruit safety testing success survival outcome systems research

项目摘要

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.

由于人口结构变化，迫切需要证据来指导老年人的临床护理，包括预期寿命的延长和最近老年人口数量的翻倍减少了心血管疾病的复发。然而，临床研究经常排除 75 岁以下患者的预防和初始事件。 75 岁以上的人由于合并症和虚弱的患病率较高，因此很少甚至没有证据表明对于寿命较长的老年人来说，预防认知障碍的前景可用于指导护理。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对于他汀类药物的有效性存在争议。用于 75 岁以上成年人的主要 CVD、痴呆和残疾预防，特别是在环境中改善认知和功能的证据。不同种族/民族和健康状况的老年人群的结果将需要新的临床试验我们提出采用可持续方法和基础设施的方法。老年人降脂事件和益处的评估），第一个针对非 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对照的实用方法。跨 PCORnet 和 VA 网络的临床试验（PCT）设计，该试验将由 Karen 博士领导 DCRI 的 Alexander、WFSM 的 Jeff Williamson 博士、DCRI 的 Adrian Hernandez 博士和 DCRI 的 Walter Ambrosius 博士该团队在设计和实施方面积累了经验和成就记录。 PCT、确定老年人认知和残疾结果的试验专业知识，并得到了强大的行政基础设施来协调这些共同的责任以取得成功。 PREVENTABLE 的目标是了解他汀类药物在老年人中的作用，在老年人群中，一级预防的风险/益处尚未得到研究，假设是在一个大型试验中进行的。老年人群将展示他汀类药物在减少痴呆、残疾和心血管事件方面的益处。我们进一步追求广泛的基因组、生化和成像辅助研究将提供独特的对这些关键结果的深入了解有以下具体目标：目标 1：确定角色。中等强度他汀类药物预防痴呆症和延长患者 75 年无残疾生存期的研究以及没有临床明显冠心病的老年人，包括体弱、身体受损的人功能、轻度认知障碍、多重用药和多重发病目标 2：确定中度的作用。强度他汀类药物预防心肌梗塞/急性冠状动脉综合征、中风、心脏住院失败、血运重建或心血管相关死亡，并预防轻度认知障碍或目标 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 份生物样本推进精准健康。