Statins To Prevent Progression of Glaucoma: The STOP Glaucoma Trial

描述（由申请人提供）：他汀类药物是一种广泛使用的药物，可降低高脂血症患者的胆固醇水平。最近的证据表明，他汀类药物还可以降低脑血管和心血管事件的风险，并可能有助于中枢神经系统疾病，包括缺血性中风、阿尔茨海默病和多发性硬化症。越来越多的证据表明，他汀类药物也可以防止OAG的恶化，OAG是世界上最常见的失明原因之一。基础科学家已经确定了几种他汀类药物可以防止OAG进展的机制，例如，通过上调内皮一氧化氮合酶来改善视神经的血流量，以及通过抑制Rho激酶活性来增强水流出。一些队列和病例对照研究表明，他汀类药物使用者的OAG或疾病稳定率降低。在初步分析中，我们分析了一组524,109名60岁以上高脂血症患者的纵向数据，这些患者来自一个大型的、全国性的管理式医疗网络，发现与不使用他汀类药物的患者相比，使用他汀类药物的患者发生OAG和从疑似青光眼发展为OAG的风险显著降低。这项R34临床试验计划拨款的目的是为开展一项大型、多中心、双盲、随机对照试验提供必要的基础设施，以确定他汀类药物是否对轻度或中度OAG患者的OAG进展起保护作用。一项显示他汀类药物可以防止青光眼恶化的随机对照试验将对患者护理具有重要的临床意义，因为它将为通过使用一种常见的药物治疗一种新的适应症来保护患者免受这种潜在致盲疾病的疾病进展提供证据基础。

DESCRIPTION (provided by applicant): Statins are a widely used class of medications that lower cholesterol levels in patients with hyperlipidemia. Recent evidence suggests that statins can also reduce the risk for cerebrovascular and cardiovascular events and may be helpful in diseases of the central nervous system, including ischemic stroke, Alzheimer disease, and multiple sclerosis. Growing evidence suggests that statin drugs may also protect against worsening of OAG, one of the most common causes of blindness worldwide. Basic scientists have identified several mechanisms by which statins may protect against OAG progression-for example, by improving blood flow to the optic nerve as a result of upregulating endothelial nitric oxide synthase, and by enhancing aqueous outflow through the inhibition of Rho kinase activity. Several cohort and case-control studies have demonstrated reduced rates of OAG or disease stabilization among statin users. In preliminary analyses, we analyzed longitudinal data on a group of 524,109 enrollees, aged 60 years or older, with hyperlipidemia in a large, nationwide, managed-care network and found that persons using a statin agent had a significantly reduced risk for developing OAG and for progressing from suspected glaucoma to OAG, compared with persons who were not using statin drugs. The aim of this R34 clinical trial planning grant is to assemble the necessary infrastructure to carry out a large, multicenter, double-masked, RCT to determine whether statins play a protective role against OAG progression in persons with mild or moderate OAG. An RCT demonstrating that statins protect against worsening of glaucoma would have important clinical implications for patient care, as it would provide an evidence basis for protecting patients from disease progression in this potentially blinding disease by using a commonly available medication for a new indication.