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：
8582967
负责人：
Gang Fang
金额：
$ 22.77万
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 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8582967
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）：急性心肌梗塞（AMI）后，老年人的死亡率，再染色，中风和心力衰竭（HF）的风险过高。高手抑制剂是AMI后推荐的预防疗法之一。然而，在我们先前的研究中，我们发现，有44％的老年AMI患者被开处方ACE抑制剂，剂量低于剂量，在随机临床 - 审判（RCTS）中具有可靠的益处。该问题的一部分可能归因于老年人的治疗效果和安全性缺乏知识和临床不确定性，因为老年人在RCT中的代表不足。如果较低剂量的ACE抑制剂比RCT中证明的剂量的益处要小，那么数十万年级的AMI患者的剂量较低，可能会使死亡，重新症状，中风和心力衰竭的风险更高。但是，如果较低剂量的ACE抑制剂具有类似的益处和较低的不良副作用风险，例如高钾血症和急性肾衰竭，在老年人中可能首选较低的剂量，以避免较高的严重不良副作用风险。这项回顾性观察队列研究将比较AMI后ACE抑制剂的现实治疗有效性和安全性的安全性与老年剂量的较低剂量。我们将使用来自新近可用的Medicare慢性慢性慢性数据仓库（CCW）和D Prescription D Part D Files中的研究文件，在2008年和2009年组建一个全国人群，由80,000名老年患者组成，并在2008年和2009年将ACE抑制剂使用。我们将使用尖端的创新分析方法，例如多重倾向分数和工具变量来解决研究问题。我们的具体目的是1）研究低和中剂量的ACE抑制剂是否具有与RCT剂量相同的临床益处。 2）调查低剂量的ACE抑制剂是否具有与老年人中RCT剂量相同的急性肾衰竭和需要住院和治疗终止的高血症复合物的严重不良副作用风险； 3）研究老年人中的低剂量ACE抑制剂是否具有与年龄组（65-74、75-84、85+）相同的临床益处和风险。老年人缺乏现实的治疗效果和安全知识可能会阻碍数十万老年患者接受最佳平衡益处和危害的疗法治疗。我们的长期目标是研究具有尖端方法的老年患者的现实治疗效应，这将补充RCT结果，更好地为临床实践提供信息，并增强临床准则和公共卫生政策的制定。