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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？

基本信息

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
项目类别：
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

项目摘要

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）：老年人急性心肌梗塞（AMI）后死亡、再梗塞、中风和心力衰竭（HF）的风险极高。高手抑制剂是 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 患者服用的 ACE 抑制剂剂量低于随机临床试验 (RCT) 中已证明有益的剂量。这一问题的部分原因可能是由于老年人在随机对照试验中代表性不足，因此对老年人的治疗有效性和安全性缺乏了解和临床不确定性。如果较低剂量的 ACE 抑制剂的益处明显低于随机对照试验中证明的剂量，那么数十万较低剂量的老年 AMI 患者可能会面临更高的死亡、再次梗塞、中风和心力衰竭的风险。然而，如果较低剂量的 ACE 抑制剂类似的益处和较低的不良副作用（如高钾血症和急性肾功能衰竭）的风险较低，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。这项回顾性观察队列研究将比较 AMI 后 ACE 抑制剂的既定 RCT 剂量与较低剂量在老年人中的实际治疗效果和安全性。我们将使用新提供的 Medicare 慢性病数据仓库 (CCW) 中的研究文件和处方 D 部分文件，在全国范围内收集 80,000 名因 AMI 出院并在 2008 年和 2009 年使用过 ACE 抑制剂的老年患者进行的队列。我们将使用多重倾向评分和工具变量等尖端创新分析方法来解决研究问题。我们的具体目标是 1) 研究低剂量和中剂量的 ACE 抑制剂在预防老年人复发性 AMI、中风、需要住院的心力衰竭、全因死亡率和所有终点的综合方面是否具有与 RCT 剂量相同的临床益处； 2）研究中低剂量的ACE抑制剂是否与老年人中的RCT剂量具有相同的严重不良副作用风险，即急性肾功能衰竭和高钾血症复合症状，需要住院和停止治疗； 3）研究低剂量和中剂量的ACE抑制剂是否与老年人年龄组（65-74、75-84、85+）的RCT剂量具有相同的临床获益和风险。缺乏对老年人的现实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利弊的疗法。我们的长期目标是利用尖端方法研究老年患者的真实治疗效果，这将补充随机对照试验结果，更好地为临床实践提供信息，并促进临床指南和公共卫生政策的制定。