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：
10021540
负责人：
KAREN P ALEXANDER
金额：
$ 1539.25万
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/10021540
关键词：
Acute myocardial infarction Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Ancillary Study Benefits and Risks Biochemical Biological 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 Placebos 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 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.

迫切需要有证据表明由于人口转变而导致老年人的临床护理，包括更长的预期寿命和最近的老年人配音。他汀类药物减少了复发性CVD事件并防止75岁以下患者的初始事件。但是，临床研究经常被排除在外由于合并症的患病率较高和脆弱的人，年龄在75岁以上的人很少，没有证据可用于指导该人群的护理。对于寿命更长的老年人，预防认知的希望损害与防止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。他汀类药物的有用性有平气对于年龄在75岁以上的成年人中，对于原发性CVD，痴呆症和残疾预防，尤其是在此环境中多种慢性病，高年龄或脆弱的情况。改善认知和功能的证据具有潜水员种族/种族和健康状况的老年人口的成果将需要新的临床试验可持续方法和基础设施的方法。我们建议可预防（务实评估老年人中脂质降低的事件和益处），第一次致汀类药物试验主要结果 - 无痴呆或持续性残疾的生存。使用安慰剂对照的务实 PCORNET和VA网络上的临床试验（PCT）设计，该试验将在Karen博士的领导下。 DCRI的Alexander，WFSM的Jeff Williamson博士，DCRI的Adrian Hernandez博士和Walter Ambrosius博士在 wfsm。该团队已经建立了设计和行为成就的经验和赛道在PCT中，在确定老年人认知和残疾结果方面的试验专业知识，并得到了强大的行政基础设施协调这些对成功的共同责任。总体可预防的目标是产生有关他汀类药物在老年人中的作用的知识，这是一个人群一级预防的风险/益处一直在研究之下。假设是在老年人将证明他汀类药物在减少痴呆，残疾和简历事件方面的好处。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洞悉这些关键结果。可预防的具体目标：目标1：确定角色现代强度的他汀类药物预防痴呆症和延长残疾生存期75年的患者且没有临床证据的冠心病，包括身体脆弱，身体受损的年龄较大功能，轻度认知障碍，多药和多种疾病。目标2：确定中等的作用强度汀类药物预防心肌基础设施/急性冠状动脉综合征，中风，心脏失败，血运重建或心血管相关死亡，并防止轻度认知障碍或失智。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种生物特异性提前精度健康。