Xanthine oxidase inhibitors and risks of myocardial infarction and diabetes

黄嘌呤氧化酶抑制剂与心肌梗塞和糖尿病的风险

基本信息

批准号：
9230337
负责人：
Seoyoung Catherine Kim
金额：
$ 20.2万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-03-01 至 2018-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9230337
关键词：
Adherence Adolescent Allopurinol American Animal Model Big Data Blood Pressure Cardiovascular Diseases Chronic Clinical Research Cohort Studies Computerized Medical Record Coronary heart disease Data Data Linkages Databases Diabetes Mellitus Effectiveness Epidemiologic Methods Ethics Excess Mortality Glaucoma Gold Gout Health Healthcare Hormone replacement therapy Hypertension Hyperuricemia Inflammatory Arthritis Insurance Intention Knowledge Laboratories Link Medical Metabolic syndrome Methods Myocardial Infarction Non-Insulin-Dependent Diabetes Mellitus Outcome Outpatients Patients Pharmaceutical Preparations Pharmacoepidemiology Prevalence Probability Protocols documentation Randomized Controlled Trials Renal function Reporting Research Research Design Risk Safety Scoring Method Selection Bias Serum Stroke Test Result Testing Time Urate Uric Acid Weight Work active comparator analog blood pressure reduction common treatment design drug efficacy efficacy study febuxostat health data improved innovation interest mortality prevent public health relevance treatment adherence treatment duration treatment effect trial comparing xanthine oxidase inhibitor

项目摘要

DESCRIPTION (provided by applicant): Gout is the most common inflammatory arthritis caused by hyperuricemia. Over the past few decades, growing evidence supports that gout and hyperuricemia are independently associated with an increased risk of hypertension, cardiovascular diseases including myocardial infarction (MI) and stroke, metabolic syndrome including type 2 diabetes mellitus (T2DM), and mortality. Several studies suggest that the excess mortality in gout patients is attributable to cardiovascular disease. Xanthine oxidase inhibitors (XOI), including allopurinol and febuxostat, lower serum uric acids and are common treatments for gout. Allopurinol has been shown to reduce blood pressure in hypertensive adolescents and improve endothelial function. Furthermore, an animal model showed a beneficial effect of allopurinol on metabolic syndrome. However, to date, it remains largely unknown whether XOIs decrease risks of gout-associated conditions such as MI and T2DM. The primary objective of this proposal is to produce high-quality evidence on the effect of XOI in preventing MI and T2DM in gout patients. The specific aims of this proposal are: 1) to examine the effect of XOI on the risk of incident MI in patients with gout, 2) to investigate the effect of XOI on the risk of incident T2DM in patients with gout and 3) to estimate the effect of XOI on MI and T2DM adjusted for treatment adherence in patients with gout. The proposed study will use data from the United HealthCare insurance claims databases (2004-2013) linked to laboratory test results, and utilize a number of rigorous and innovative approaches for pharmacoepidemiologic research and causal inference to study the effects of XOI on MI and T2DM risks. Given the increasing interest in big data and data linkage in clinical research, it is important to understand the value of using a claims database linked to outpatient lab test results for pharmacoepidemiologic research and to determine the best strategy to incorporate lab data for further confounding control. This proposed study will make an important contribution because it will be the first and largest to investigate the effects of XOI on major medical conditions such as MI and T2DM, adjusting for adherence. Furthermore, the proposed, advanced and innovative epidemiologic methods will extend our understanding of how to deal with confounding by indication, time-varying selection bias, and missing data on laboratory test values in pharmacoepidemiologic research.

描述（由申请人提供）：痛风是由高尿酸血症引起的最常见的炎症性关节炎。在过去的几十年中，越来越多的证据支持痛风和高尿酸血症与高血压、包括心肌梗塞（MI）和心血管疾病的风险增加独立相关。中风、代谢综合征（包括 2 型糖尿病 (T2DM)）和死亡率多项研究表明，痛风患者死亡率过高可归因于心血管疾病。抑制剂（XOI），包括别嘌呤醇和非布索坦，可以降低血清尿酸，是痛风的常见治疗方法，已被证明可以降低高血压青少年的血压并改善内皮功能。此外，动物模型显示别嘌呤醇对代谢有有益作用。然而，迄今为止，未知的 XOIs 是否会降低 MI 和 T2DM 等痛风相关疾病的风险仍然存在很大的疑问。提供关于 XOI 在预防痛风患者 MI 和 T2DM 方面的作用的高质量证据该提案的具体目的是：1) 检查 XOI 对痛风患者发生 MI 风险的影响，2) 进行调查。的效果 XOI 对痛风患者发生 T2DM 风险的影响，以及 3) 评估 XOI 对痛风患者治疗依从性调整后的 MI 和 T2DM 的影响。拟议的研究将使用来自 United HealthCare 保险索赔数据库的数据（2004-2013 年）。）与实验室测试结果相联系，并利用许多严格和创新的方法进行药物流行病学研究和因果推断，以研究 XOI 对 MI 和 T2DM 风险的影响。由于临床研究中的大数据和数据链接，了解使用与门诊实验室测试结果相关的索赔数据库进行药物流行病学研究的价值并确定合并实验室数据以进一步控制混杂的最佳策略非常重要。这是一项重要的贡献，因为这将是第一个也是最大的研究 XOI 对 MI 和 T2DM 等主要疾病的影响，并根据依从性进行调整。此外，所提出的先进和创新的流行病学方法将扩展我们对如何应对的理解。混淆药物流行病学研究中的适应症、随时间变化的选择偏差和实验室检测值缺失数据。