Stimulants and Vascular Events in ADHD

描述（由申请人提供）：有相当多的公众和专业人士担心，两种最广泛用于青少年注意力缺陷/多动障碍（ADHD）的兴奋剂，安非他明混合盐（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。这些安全性问题是基于接受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作用。然而，由于大型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，在多大程度上以及在什么条件下增加了年轻人血管事件的风险。本研究将检查兴奋剂治疗与6 - 21岁青少年ADHD患者心肌梗死、中风、短暂性脑缺血、心绞痛和心律失常风险之间的关系。我们的主要目的是：1)评估ADHD的兴奋剂治疗是否会增加血管事件的风险；2)确定与MPH相比，MAS是否与更大的血管事件风险相关，以及血管事件风险是否与更长的兴奋剂治疗时间（而不是更短的兴奋剂治疗时间）相关性更强；3)检查患者的年龄、性别、合并症和易患血管疾病的合用药物是否调节MPH和MAS对血管事件风险的影响；4)评估血管事件的风险是否在兴奋剂开始或剂量增加后不久增加。我们将使用Cox比例风险模型和与兴奋剂治疗时间相关的病例交叉分析来评估这些关联。来自大型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在何种临床情况下MPH和MAS是否会增加年轻人血管事件的风险。将提取有关兴奋剂治疗模式和35万多名青少年治疗ADHD的血管事件发生率的数据。这些数据的规模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。该结果将直接为未来的实践研究以及临床和监管工作提供信息，以提高兴奋剂治疗在ADHD儿童社区管理中的安全性。

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.