Xanthine oxidase inhibitors and risks of myocardial infarction and diabetes

 描述(申请人提供)：痛风是最常见的炎症性关节炎，由高尿酸血症引起。在过去的几十年里，越来越多的证据支持痛风和高尿酸血症与高血压、包括心肌梗死(MI)和中风的心血管疾病、包括2型糖尿病(T2 DM)的代谢综合征和死亡率的增加独立相关。几项研究表明，痛风患者的高死亡率可归因于心血管疾病。黄嘌呤氧化酶抑制剂(XOI)，包括别嘌醇和非布司坦，降低血清尿酸，是痛风的常用治疗方法。别嘌醇已被证明可以降低高血压青少年的血压，并改善血管内皮功能。此外，动物模型显示别嘌醇对代谢综合征有有益的影响。然而，到目前为止，XOIS是否能降低痛风相关疾病(如MI和T2 DM)的风险在很大程度上仍不清楚。这项建议的主要目的是提供高质量的证据，证明XOI在预防痛风患者MI和T2 DM方面的效果。这项建议的具体目的是：1)检查XOI对痛风患者发生心肌梗死的风险的影响；2)调查XOI对痛风患者发生MI的影响 XOI对痛风患者发生T2 DM的风险以及3)评估XOI对痛风患者MI和T2 DM的影响。这项拟议的研究将使用与实验室测试结果相关联的联合医疗保险索赔数据库(2004-2013)的数据，并利用药物流行病学研究和因果推断的一些严格和创新的方法来研究XOI对MI和T2 DM风险的影响。鉴于临床研究中对大数据和数据联系的兴趣与日俱增，了解将索赔数据库与门诊实验室检测结果链接起来进行药物流行病学研究的价值，并确定纳入实验室数据以进一步进行混淆控制的最佳策略是很重要的。这项拟议的研究将做出重要贡献，因为它将是第一个也是最大规模的调查XOI对主要医疗条件(如MI和T2 DM)的影响，并对依从性进行调整。此外，提出的、先进的和创新的流行病学方法将扩大我们对如何处理药物流行病学研究中因适应症、时变的选择偏差和实验室测试值丢失数据而造成的混淆的理解。

 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.