Stimulants and Vascular Events in ADHD

多动症中的兴奋剂和血管事件

• 批准号: 7588631
• 负责人: MARK OLFSON
• 金额: $ 21.36万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-05 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7588631
• 关键词: Adolescent; Adverse event; Affect; Age; Amphetamines; Arrhythmia; Attention deficit hyperactivity disorder; Blood Vessels; Cardiovascular system; Characteristics; Child; Clinical; Clinical effectiveness; Communities; Community Practice; Cox Proportional Hazards Models; Data; Disease; Dose; Epidemiologic Methods; Event; Foundations; Funding; Future; Gender; Goals; Heart; Incidence; Intervention; Label; Measures; Medical; Methylphenidate; Monitor; Myocardial Infarction; Outcome; Parents; Patients; Pattern; Perception; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Physicians; Policies; Population; Practice based research; Records; Reporting; Research; Risk; Risk Factors; Safety; Salts; Series; Severities; Stroke; Sudden Death; Survival Analysis; System; Techniques; Time; Transient Cerebral Ischemia; United States; Variant; Vascular Diseases; Youth; base; cardiovascular risk factor; cerebrovascular; chronotropic; dosage; high risk; improved; knowledge base; patient population; policy implication; population based; public health relevance; surveillance data

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.

描述（由申请人提供）：公众和专业人士非常关注注意力缺陷/多动障碍（ADHD）青少年最广泛使用的两种兴奋剂，安非他明（MAS）和哌醋甲酯（MPH）的混合盐，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的已知升压和变时作用。然而，由于大量基于人群的研究以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何种条件下增加年轻人血管事件的风险。本研究将检查兴奋剂治疗与6至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。我们的主要目标是：1）评估ADHD的刺激治疗是否增加血管事件的风险; 2）确定MAS是否与比MPH更大的血管事件风险相关，以及血管事件的风险是否与更长而不是更短的刺激治疗持续时间更密切相关; 3）检查患者年龄、性别、易患血管疾病的共病医学疾病和共同处方药物可缓解MPH和MAS对血管事件风险的影响;和4）评估在开始使用兴奋剂或增加剂量后不久血管事件的风险是否增加。我们将使用考克斯比例风险模型和病例交叉分析与兴奋剂治疗的时间依赖性措施，以评估这些协会。来自大型私人保险患者人群的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增加年轻人血管事件的风险。将提取有关超过35万名接受ADHD治疗的青少年的兴奋剂治疗模式和血管事件发生率的数据。这些数据的大小和范围为评价兴奋剂对血管事件风险的影响提供了难得的机会。这些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ADHD儿童社区管理中兴奋剂治疗的安全性。 公共卫生相关性：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会增加这些风险，增加到什么程度，以及在什么条件下。这项基于人群的研究将确定兴奋剂治疗是否会增加注意力缺陷多动障碍（ADHD）青少年发生严重血管事件的风险，并将确定风险特别高的青少年。研究结果将直接为改善ADHD社区管理中兴奋剂治疗安全性的努力提供信息。