Informing optimal first-line antihypertensive therapy: A rigorous comparative effectiveness analysis of ARBs vs. ACEIs on long-term risk of dementia, cancer, heart disease, and quality of life

为最佳一线抗高血压治疗提供信息：ARB 与 ACEI 对痴呆、癌症、心脏病和生活质量长期风险的严格比较有效性分析

• 批准号: 10340245
• 负责人: Adam P Bress
• 金额: $ 80.87万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10340245
• 关键词: Accounting; Address; Adult; Affect; Aging; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Angiotensin II Receptor; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; California; Cardiovascular Diseases; Chronic Disease; Clinical; Code; Cognition; Cognitive; Comprehensive Health Care; Coronary; Data; Data Analyses; Data Sources; Dementia; Drug Prescriptions; Electronic Health Record; Event; Fibrosis; Goals; Guidelines; Health; Health Benefit; Heart Diseases; Heart failure; Hypertension; Incidence; Individual; Inflammation; Knowledge; Life Expectancy; Long-Term Effects; Longevity; Malignant Neoplasms; Methods; Modernization; Morbidity - disease rate; Myocardial Infarction; Natural Language Processing; Organ; Outcome; Oxidative Stress; Patient-Focused Outcomes; Patients; Persons; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacology; Physiological; Population; Prevalence; Public Health; Quality of life; Race; Randomized Controlled Trials; Regimen; Renin-Angiotensin System; Research; Risk Factors; Safety; Socioeconomic Status; Stroke; Subgroup; Time; Veterans; Veterans Health Administration; active comparator; base; comparative; comparative effectiveness analysis; cost efficient; dementia risk; design; experience; follow-up; frailty; improved; interest; medication compliance; modifiable risk; mortality; multiple chronic conditions; patient oriented; population health; prevent; sex; treatment adherence; treatment effect; vasoconstriction

PROJECT SUMMARY Hypertension (HTN) prevalence increases with aging and is a leading risk factor for several chronic illnesses including Alzheimer's disease and related dementias (ADRD), cardiovascular disease (CVD), and several cancers, as well as mortality. Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) are two of the most commonly prescribed anti-HTN classes, used by ~40 million US adults. ARBs and ACEIs and have distinctive beneficial downstream effects on physiologic abnormalities in HTN, including vasoconstriction, inflammation, fibrosis, and oxidative stress, which in turn may result in different long-term risks of ADRD and multimorbidity associated with aging. However, current HTN guidelines recommend prescribing ARBs and ACEIs interchangeably due to presumed equivalent benefit and safety. Our goal is to optimize initial anti-HTN medication prescribing by clarifying the optimal first choice RAS-blocker between ARBs vs. ACEIs. Because ~23 million US adults are currently taking an ACEI and physiologic evidence supports differences in downstream effects of these medications, even if ARBs are only 15% more effective, the long-term population health impact of switching first-line RAS-blockade from ACEI to ARB would be enormous. We will leverage data from the Veterans Health Administration (VHA) and Kaiser Permanente Southern California (KP SoCal) to evaluate the effects of ARBs vs. ACEIs on the risk of ADRD, multimorbidity, frailty, and health-adjusted life expectancy (HALE; the amount of time one can expect to live accounting for one's cumulative morbidity burden). The VHA and KP SoCal are ideal data sources to perform this research because they include comprehensive healthcare information for >10 million patients, collect detailed information on medication use and health outcomes, and have high patient retention with >10 years of follow- up. The specific aims are to determine long-term comparative effects, including duration of use, of ARB- vs. ACEI-based anti-HTN medication regimens on (Aim 1) the incidence of ADRD, CVD (stroke, myocardial infarction, coronary revascularization, or heart failure), and cancers, separately and (Aim 2) the patient- centered outcome of frailty and the population-centered outcome of HALE. We will use an active comparator, new-user design accounting for medication adherence, as well as natural language processing to ascertain ADRD more accurately in the electronic health record over using administrative codes alone. Our team is well- suited to perform the study given considerable prior experience analyzing VHA and KP data, including pharmacoepidemiologic analyses of anti-HTN medication use; assessment of ADRD, CVD incidence, cancer incidence, and multimorbidity; and application of causal inference methods. Our project could support a paradigm shift of first-choice RAS-blockade. Current projections indicate that ADRD will affect >115 million people by 2050 and cancer incidence will be 27 million per year by 2040. The potential public health benefit of addressing these knowledge gaps and, thereby, improving the quality and length of life is enormous.

项目概要 高血压 (HTN) 患病率随着年龄的增长而增加，是多种慢性疾病的主要危险因素 包括阿尔茨海默氏病和相关痴呆症 (ADRD)、心血管疾病 (CVD) 和多种疾病 癌症，以及死亡率。血管紧张素 II 受体阻滞剂 (ARB) 和血管紧张素转换酶 抑制剂 (ACEIs) 是两种最常用的抗 HTN 药物，约有 4000 万美国成年人使用。 ARB 和 ACEI 对 HTN 的生理异常具有独特的有益下游作用， 包括血管收缩、炎症、纤维化和氧化应激，这反过来又可能导致不同的结果 ADRD 和与衰老相关的多种疾病的长期风险。然而，当前的 HTN 指南 由于假定疗效和安全性相同，建议交替使用 ARB 和 ACEI。我们的 目标是通过明确最佳首选 RAS 阻滞剂来优化初始抗 HTN 药物处方 ARB 与 ACEI 之间的比较。因为目前约有 2300 万美国成年人正在服用 ACEI 和生理药物 有证据支持这些药物的下游效应存在差异，即使 ARB 只多出 15% 如果有效，将一线 RAS 阻断从 ACEI 切换为 ARB 的长期人口健康影响将 是巨大的。我们将利用退伍军人健康管理局 (VHA) 和 Kaiser Permanente 的数据 南加州 (KP SoCal) 评估 ARB 与 ACEI 对 ADRD、多发病、 虚弱和健康调整预期寿命（HALE；一个人可以预期生存的时间 一个人的累积发病负担）。 VHA 和 KP SoCal 是执行这项研究的理想数据源 因为它们包含超过 1000 万患者的综合医疗保健信息，所以收集详细的 有关药物使用和健康结果的信息，并且具有较高的患者保留率（超过 10 年的随访） 向上。具体目标是确定 ARB 与其他药物的长期比较效果，包括使用持续时间。 基于 ACEI 的抗 HTN 药物治疗方案对（目标 1）ADRD、CVD（中风、心肌梗死）发生率的影响 梗塞、冠状动脉血运重建或心力衰竭）和癌症，以及（目标 2）患者- 以衰弱为中心的结果和以人群为中心的 HALE 结果。我们将使用有源比较器， 新用户设计考虑了药物依从性，以及自然语言处理来确定 与单独使用管理代码相比，ADRD 在电子健康记录中更加准确。我们的团队很好—— 鉴于之前有大量分析 VHA 和 KP 数据的经验，适合进行该研究，包括 抗 HTN 药物使用的药物流行病学分析； ADRD、CVD 发病率、癌症的评估 发病率和多重发病率；以及因果推理方法的应用。我们的项目可以支持 首选 RAS 封锁的范式转变。目前的预测表明 ADRD 将影响超过 1.15 亿人 到 2050 年，癌症发病率将达到每年 2700 万。到 2040 年，癌症发病率将达到每年 2700 万。 解决这些知识差距，从而提高生活质量和延长寿命是巨大的。