Stimulants and Vascular Events in ADHD

描述(由申请人提供)：有相当大的公众和专业关注，两种最广泛的处方青少年注意缺陷/多动障碍(ADHD)的兴奋剂，苯丙胺混合盐(MAS)和哌醋甲酯(MPH)，可能会增加中风，心肌梗死和其他血管事件的风险。这些安全问题是基于接受MAS和MPH治疗的患者发生血管疾病的自发不良事件报告，以及这些兴奋剂已知的升压和变时性作用。然而，由于大规模的基于人群的研究之前没有比较接受和不接受这些兴奋剂的年轻人的血管事件发生率，没有人知道MAS和MPH是否会在多大程度上以及在什么情况下增加年轻人发生血管事件的风险。本研究将在接受ADHD治疗的6至21岁的年轻人中，研究兴奋剂治疗与心肌梗死、中风、短暂性脑缺血、心绞痛和心律失常风险之间的关系。我们的主要目标是：1)评估ADHD的刺激治疗是否会增加血管事件的风险；2)确定MAS是否与MPH相比血管事件的风险更高，以及血管事件的风险是否与较长的刺激剂治疗时间更密切相关；3)检查患者的年龄、性别、合并内科疾病和易患血管疾病的联合处方药是否缓和了MPH和MAS对血管事件风险的影响；以及4)评估在兴奋剂开始使用或剂量增加后不久血管事件的风险是否增加。我们将使用COX比例风险模型和病例交叉分析以及时间依赖的兴奋剂治疗措施来评估这些关联。来自大量私人保险患者群体的11年综合处方和索赔数据将用于确定MPH和MAS是否以及在何种临床情况下会增加年轻人发生血管事件的风险。将摘录有关兴奋剂治疗模式和超过350,000名接受ADHD治疗的青少年的血管事件发生率的数据。这些数据的大小和范围为评估兴奋剂对血管事件风险的影响提供了难得的机会。这一结果将直接为未来基于实践的研究以及临床和监管努力提供信息，以提高ADHD儿童社区管理中兴奋剂治疗的安全性。 与公共健康相关：尽管人们担心最常用的兴奋剂可能会增加中风、心脏病发作和其他严重血管事件的风险，但没有人知道兴奋剂是否、在多大程度上以及在什么条件下实际上增加了这些风险。这项以人群为基础的研究将确定兴奋剂治疗是否会增加患有注意力缺陷/多动障碍(ADHD)的青年发生严重血管事件的风险，并将确定特别高危的青年。这一结果将直接为改善ADHD社区管理中兴奋剂治疗的安全性提供参考。

DESCRIPTION (provided by applicant): There is considerable public and professional concern that the two most widely prescribed stimulants for youth with attention-deficit/hyperactivity disorder (ADHD), mixed salts of amphetamine (MAS) and methylphenidate (MPH), may increase the risk of stroke, myocardial infarction, and other vascular events. These safety concerns are based on spontaneous adverse event reports of vascular disease developing in patients receiving MAS and MPH and the known pressor and chronotropic effects of these stimulants. Yet because large population-based studies have not previously compared the rate of vascular events among youth who do and do not receive these stimulants, no one knows whether, to what extent, and under what conditions MAS and MPH increase the risk of vascular events in young people. This study will examine associations between stimulant treatment and risk of myocardial infarction, stroke, transient cerebral ischemia, angina, and arrhythmia in youth, ages 6 to 21 years, treated for ADHD. Our primary aims are to: 1) evaluate whether stimulant treatment of ADHD increases the risk of vascular events; 2) determine whether MAS is associated with a greater risk of vascular events than MPH and whether the risk of vascular events is more strongly related to longer as opposed to shorter duration of stimulant treatment; 3) examine whether patient age, gender, comorbid medical diseases and co-prescribed medications that predispose to vascular disease moderate the effects of MPH and MAS on the risk of vascular events; and 4) assess whether risk of vascular events increases shortly after stimulant initiation or dosage increase. We will use Cox proportional hazards models and case crossover analyses with time dependent measures of stimulant treatment to assess these associations. Eleven years of integrated prescription and claims data from a large privately insured patient population will be used to determine whether and under what clinical circumstances MPH and MAS increase the risk of vascular events in young people. Data will be extracted concerning the pattern of stimulant treatment and incidence of vascular events of over 350,000 youth treated for ADHD. The size and scope of this data provide a rare opportunity to evaluate effects of stimulants on risk of vascular events. The results will directly inform future practice-based research as well as clinical and regulatory efforts to improve the safety of stimulant treatment in the community management of children with ADHD. PUBLIC HEALTH RELEVANCE: Despite concern that the most commonly prescribed stimulants may increase the risk of stroke, heart attacks, and other serious vascular events, no one knows whether, to what extent, and under what conditions stimulants actually increase these risks. This population-based study will determine whether stimulant treatment increases the risk of serious vascular events in youth with attention-deficit/hyperactivity disorder (ADHD) and will identify youth at especially high risk. The results will directly inform efforts to improve the safety of stimulant treatment in the community management of ADHD.