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: 10225636
• 负责人: Adam P Bress
• 金额: $ 67.17万
• 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/10225636
• 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; Machine Learning; Measures; Memory; Methods; Modernization; Outcome; Patients; 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 intervention; blood pressure regulation; brain volume; clinical practice; clinically significant; cognitive benefits; comparative; cost; cost efficient; dementia risk; design; disability; experience; follow-up; machine learning method; 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.

项目总结