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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.