Should the elderly have lower dose of ACE inhibitors for prevention after AMI?

老年人发生 AMI 后是否应该使用较低剂量的 ACE 抑制剂来预防？

• 批准号: 8691638
• 负责人: Gang Fang
• 金额: $ 18.96万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8691638
• 关键词: Accounting; Acute Kidney Failure; Acute myocardial infarction; Address; Adverse effects; Affect; Age; Age-Years; Aging; American; American Heart Association; Angiotensin-Converting Enzyme Inhibitors; Benefits and Risks; Cardiac; Cardiology; Cardiovascular system; Cessation of life; Chronic; Clinical; Cohort Studies; Complement; Data; Data Sources; Databases; Development; Dose; Effectiveness; Elderly; Elderly man; Elderly woman; Equilibrium; Event; Foundations; Goals; Guidelines; Health Policy; Healthcare; Heart failure; Hospitalization; Hospitals; Infarction; Institution; Knowledge; Medicare; Methods; Myocardial Infarction; Natural experiment; Patients; Peptidyl-Dipeptidase A; Persons; Population; Prevention; Prevention therapy; Preventive; Public Health; Quality of Care; Randomized Clinical Trials; Randomized Controlled Trials; Recurrence; Renin; Research; Risk; Risk Adjustment; Safety; Secondary Prevention; Stroke; Subgroup; Sudden Death; Treatment Effectiveness; Uncertainty; United States; Variant; acute coronary syndrome; age group; analytical method; base; clinical practice; cohort; college; comparative effectiveness; comparative treatment; cost; high risk; hyperkalemia; improved; innovation; instrument; mortality; novel; older patient; prevent; public health relevance; response; treatment effect

DESCRIPTION (provided by applicant): Older adults have excessively higher risk for mortality, reinfarction, stroke and heart failure (HF) after acute myocardial infarction (AMI). ACE inhibitors are one of the recommended preventive therapies after AMI. In our previous study, however, we found that 44% of elderly AMI patients were prescribed ACE inhibitors at doses lower than the doses with proven benefits in randomized-clinical-trial (RCTs). Part of this problem may be attributed to the lack of knowledge and clinical uncertainty on the treatment effectiveness and safety in the elderly since the elderly are insufficiently represented in the RCTs. If lower doses of ACE inhibitors have significant less benefit than the doses proven in RCTs, hundreds of thousands elderly AMI patients with lower doses may be put at a higher risk for death, re-infarction, stroke, and heart failure. However, if lower doses of ACE inhibitors have similar benefits and lower risk of adverse side effects such as hyperkalemia and acute renal failure, lower doses may be preferred in the elderly to avoid higher risk of severe adverse side effects. This retrospective observational cohort study will compare the real-world treatment effectiveness and safety of the established RCT doses of ACE inhibitors post AMI versus lower doses in the elderly. We will assemble a nationwide cohort of 80,000 elderly patients who were discharged with AMI and had ACE inhibitors usage in 2008 and 2009 using the research files from the newly available Medicare Chronic Condition Data Warehouse (CCW) and prescription Part D files. We will use cutting-edge innovative analytical methods such as multiple propensity scores and instrumental variables to address the research question. Our specific aims are 1) to investigate whether low and medium doses of ACE inhibitors have the same clinical benefit as the RCT doses in the prevention of recurrent AMI, stroke, heart failure requiring hospitalization, all-cause mortality, and composite of all end points in the elderly; 2) to investigate whether low and medium doses of ACE inhibitors have the same severe adverse side effects risk of a composite of acute renal failure and hyperkalemia requiring hospitalization and treatment discontinuation as the RCT doses in the elderly; and 3) investigate whether low and medium doses of ACE inhibitors have the same clinical benefit and risk as the RCT doses by age groups (65-74, 75-84, 85+) in the elderly. The lack of real-world treatment effectiveness and safety knowledge in the elderly may hinder hundreds of thousands elderly patients to be treated with therapies that optimally balance benefits and harms. Our long- term goal is to investigate real-world treatment effects among elderly patients with cutting-edge methods, which will complement RCT results, better inform clinical practice, and enhance the development of clinical guidelines and public health policies.

描述（由申请人提供）：老年人急性心肌梗死（AMI）后死亡、再梗死、卒中和心力衰竭（HF）的风险极高。Ace 抑制剂是AMI后推荐的预防性治疗之一。然而，在我们之前的研究中，我们发现44%的老年AMI患者使用的ACE抑制剂剂量低于随机临床试验（RCT）中已证实的获益剂量。这一问题的部分原因可能是对老年人治疗有效性和安全性缺乏了解和临床不确定性，因为老年人在RCT中的代表性不足。如果较低剂量的ACE抑制剂的获益显著低于RCT中证实的剂量，则数十万低剂量的老年AMI患者可能面临更高的死亡、再梗死、中风和心力衰竭风险。然而，如果较低剂量的ACE抑制剂 类似的益处和不良副作用如高钾血症和急性肾衰竭的较低风险，老年人可能优选较低剂量，以避免严重不良副作用的较高风险。这项回顾性观察性队列研究将比较AMI后ACE抑制剂既定RCT剂量与较低剂量在老年人中的真实治疗有效性和安全性。我们将收集一个全国范围内的80，000名老年患者队列，这些患者在2008年和2009年因AMI出院并使用ACE抑制剂，使用来自新提供的Medicare慢性疾病数据仓库（CCW）和处方D部分文件的研究文件。我们将使用尖端的创新分析方法，如多重倾向评分和工具变量来解决研究问题。我们的具体目标是：1）研究低剂量和中等剂量的ACE抑制剂在预防老年人复发性AMI、卒中、需要住院治疗的心力衰竭、全因死亡率和所有终点的复合终点方面是否具有与RCT剂量相同的临床获益;（二）研究低剂量和中等剂量的ACE抑制剂是否具有相同的急性肾衰竭和高钾血症复合严重不良副作用风险需要住院治疗和治疗中止作为老年人的RCT剂量;和3）研究低剂量和中等剂量的ACE抑制剂是否具有与老年人年龄组（65-74，75-84，85+）的RCT剂量相同的临床获益和风险。老年人缺乏真实世界的治疗有效性和安全性知识，可能会阻碍数十万老年患者接受最佳平衡获益和危害的治疗。我们的长期目标是用尖端方法研究老年患者的真实治疗效果，这将补充RCT结果，更好地为临床实践提供信息，并加强临床指南和公共卫生政策的制定。