Guiding next steps for SPRINT-MIND implementation: Identifying high-benefit subgroups and comparative effects of ARB- vs. ACEI-based regimens

指导 SPRINT-MIND 实施的后续步骤：确定高效益亚组以及 ARB 与基于 ACEI 的治疗方案的比较效果

• 批准号: 10392453
• 负责人: Adam P Bress
• 金额: $ 67.38万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10392453
• 关键词: Address; Affect; Aging; Alzheimer' s disease related dementia; Ancillary Study; Angiotensin II Receptor; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benefits and Risks; Blood Pressure; Brain; Brain imaging; Calcium Channel Blockers; Cardiovascular system; Characteristics; Cognition; Cognitive; Data; Data Sources; Dementia; Dependence; Diabetes Mellitus; Diuretics; Dose; Elderly; Event; Health Benefit; Healthcare Systems; Human; Hypertension; Impaired cognition; Incidence; Intervention Trial; Kidney; Knowledge; Lead; Lesion; Measures; Memory; Methods; Modernization; Outcome; Patients; Persons; Pharmaceutical Preparations; Population; Prevention; Prevention approach; Preventive; Public Health; Randomized; Randomized Clinical Trials; Regimen; Relative Risks; Renin-Angiotensin-Aldosterone System; Research; Risk; Risk Reduction; Safety; Sample Size; Serious Adverse Event; Structure; Subgroup; Testing; active comparator; adjudicate; base; blood pressure control; blood pressure intervention; brain volume; clinical practice; clinically significant; cognitive benefits; comparative; cost; cost efficient; dementia risk; design; disability; experience; follow-up; machine learning method; machine learning prediction; middle age; mild cognitive impairment; older patient; predictive modeling; randomized trial; response; secondary analysis; tool; white matter

PROJECT SUMMARY Alzheimer’s disease and related dementias (ADRD) are the leading cause of dependence and disability in the elderly population worldwide, costing the US healthcare system over $200 billion annually. Because ADRD represents a continuous irreversible physical and cognitive decline, identifying effective approaches for its prevention is imperative. Hypertension, particularly in midlife, is associated with an increased risk of cognitive decline and ADRD. Recent data from the randomized Systolic Blood Pressure (SBP) Intervention Trial (SPRINT) Memory and cognition IN Decreased hypertension (SPRINT MIND) demonstrated that intensive SBP control (<120 mmHg) reduced the combined incidence of adjudicated mild cognitive impairment (MCI) and probable dementia, as well as abnormal white matter lesion (WML) volume compared to standard BP control (<140 mmHg) over five years follow up. To maximize public health impact, it is critical to identify which patients derive the greatest cognitive and net (overall) benefit from intensive SBP treatment and if cognitive benefits were due to direct effects of specific antihypertensive medications on cognition independent of, or in addition to, their BP-lowering effect. Prior animal and human studies, as well as our preliminary data, suggest that angiotensin II receptor blockers (ARB) have greater effects on cognition than angiotensin-converting- enzyme inhibitors (ACEI). If verified, this finding would be significant since ARBs and ACEIs are currently among the medications most commonly prescribed to older adults and are thought to be equivalent in benefit and safety. Our objective is to answer remaining questions of how to safely implement SPRINT in older patients most likely to derive cognitive benefits from intensive SBP treatment. With its large sample size, 5 years follow-up, and high-quality repeated measures of rigorously adjudicated cognitive outcomes, brain imaging, and antihypertensive medication use, SPRINT MIND provides a unique, cost-efficient, and ideal setting to answer these questions. We aim to: (1) develop and validate a prediction tool that quantifies patients’ expected cognitive benefits and net (overall) benefit incorporating cognitive and cardiovascular benefit and risk of SAEs under intensive SBP treatment, and (2) determine comparative effects, including dose-response, of ARB- vs. ACEI-based antihypertensive medication regimens on cognitive and brain structure outcomes independent of SBP-lowering effects. Though SPRINT MIND is among the first randomized trials to demonstrate a beneficial preventive effect on cognition, it is uncertain how SPRINT-MIND should be implemented and in which patients. Successful completion of this project will guide next steps for implementation by determining: (1) which patients derive the greatest cognitive and net (overall) benefit from intensive SBP treatment and (2) if ARBs have greater beneficial effects on cognitive outcomes and WML volume than ACEIs, independent of their similar SBP lowering effects.

项目概要 阿尔茨海默氏病和相关痴呆症 (ADRD) 是导致依赖和残疾的主要原因 全球老年人口每年给美国医疗保健系统造成超过 2000 亿美元的损失。 代表着持续不可逆转的身体和认知衰退，需要找到有效的方法来应对 预防势在必行。高血压，尤其是中年时期的高血压，与认知风险增加有关。 随机收缩压 (SBP) 干预试验的最新数据。 (SPRINT) 记忆力和认知能力降低 高血压 (SPRINT MIND) 表明强化 SBP 控制 (<120 mmHg) 降低了判定的轻度认知障碍 (MCI) 的综合发生率 和可能的痴呆，以及与标准血压相比异常的白质病变 (WML) 体积 五年随访期间控制（<140 mmHg） 为了最大限度地提高公共卫生影响，确定哪些因素至关重要。 患者从强化 SBP 治疗中获得最大的认知和净（总体）益处，并且如果认知 益处是由于特定抗高血压药物对认知的直接影响，独立于或依赖于 此外，之前的动物和人体研究以及我们的初步数据表明它们具有降低血压的作用。 血管紧张素 II 受体阻滞剂 (ARB) 对认知的影响比血管紧张素转换药更大 如果得到证实，这一发现将具有重要意义，因为 ARB 和 ACEI 目前都是有效的。 是最常给老年人开的药物之一，并且被认为具有相同的功效 我们的目标是回答如何在老年人中安全实施 SPRINT 的剩余问题。 由于样本量较大，最有可能从强化 SBP 治疗中获得认知益处的患者为 5。 多年的随访，以及对严格判定的认知结果的高质量重复测量，大脑 成像和抗高血压药物的使用，SPRINT MIND 提供了独特的、具有成本效益的、理想的 我们的目标是：（1）开发并验证量化的预测工具。 患者的预期认知益处和包含认知和认知的净（总体）益处 强化 SBP 治疗下的心血管益处和 SAE 风险，以及 (2) 确定比较 ARB 与基于 ACEI 的抗高血压药物治疗方案对患者的影响，包括剂量反应 尽管 SPRINT MIND 的影响与认知和大脑结构结果无关。 在首批证明对认知有益的预防作用的随机试验中，尚不确定如何 SPRINT-MIND 应该得到实施，并且患者将成功完成该项目。 通过确定以下内容来指导后续实施步骤：(1) 哪些患者获得最大的认知和认知能力 强化 SBP 治疗的净（总体）效益以及 (2) ARB 是否对认知具有更大的有益作用 与 ACEI 相比，结果和 WML 体积均优于 ACEI，无论其相似的 SBP 降低作用如何。