Comparative Safety of Pain Medications

止痛药的比较安全性

• 批准号: 9896770
• 负责人: Cecilia Pilar Chung
• 金额: $ 54.66万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9896770
• 关键词: Address; Adrenergic Agents; Affect; American; Amitriptyline; Analgesics; Anticonvulsants; Benefits and Risks; Binding; Blood Pressure; Calcium; Calcium Channel; Calibration; Cardiomyopathies; Cardiotoxicity; Cardiovascular system; Case Study; Catecholamines; Cessation of life; Clinical; Clinical Research; Clinical Trials; Congestive Heart Failure; Data; Databases; Drug Controls; Drug Evaluation; Drug usage; Epidemic; European; Event; Face; Health; Heart Arrest; Heart Rate; Heart failure; Hospitalization; Hypotension; Individual; Inotropism; Intervention; Knowledge; Liquid substance; Long-Term Effects; Longitudinal Studies; Medicare; Medicine; Methods; Muscle relaxants; Myocardial Infarction; Norepinephrine; Opioid Analgesics; Outcome; Outcome Study; Pain Management Method; Patients; Pharmaceutical Preparations; Pharmacoepidemiology; Play; Productivity; Public Health; Randomized Controlled Trials; Recording of previous events; Research Personnel; Retrospective cohort study; Risk; Role; Safety; Serotonin; Signal Transduction; Stress cardiomyopathy; Structure; Sum; Techniques; Testing; Time; Toxic effect; Treatment Efficacy; Treatment outcome; United States Food and Drug Administration; Vulnerable Populations; alternative treatment; attenuation; beneficiary; cardiovascular risk factor; chronic pain; chronic pain patient; cohort; comorbidity; comparative; cost; design; drug mechanism; duloxetine; epidemiology study; gabapentin; high dimensionality; high risk; improved; inhibitor/antagonist; medication safety; non-cancer chronic pain; non-opioid analgesic; novel; pregabalin; prescription opioid; pressure; reuptake; safety outcomes; side effect; voltage

Project Summary Clinicians, patients, and researchers encounter numerous challenges in their efforts to treat chronic pain effectively and safely. Chronic pain affects approximately 1 out of 3 Americans and costs up to $635 billion a year for treatment and lost productivity; the excessive prescription of opioids has escalated into a crisis. Non- opioid pain medications are one alternative treatment method for pain management; however, data on these medications are limited to clinical studies that lacked the power to evaluate safety outcomes appropriately. Despite the crucial role of clinical trials in establishing treatments’ efficacy, many drugs have had unforeseen and serious long-term side effects. Pharmacoepidemiologic studies offer the opportunity to study these risks, particularly among vulnerable populations often excluded from clinical trials. We propose three such studies aimed to provide critical information about the cardiovascular risks associated with the use of three widely prescribed non-opioid medications used to treat patients with chronic pain: cyclobenzaprine (muscle relaxant), duloxetine (serotonin-norepinephrine reuptake inhibitor), and pregabalin (analgesic anticonvulsant). We selected these drugs for the following reasons: 1) they are used by millions of patients; 2) multiple case reports raise concern for increased risk of serious cardiovascular events; and 3) their mechanisms of action raise significant concern about cardiovascular toxicity. More specifically, cyclobenzaprine is structurally similar to amitriptyline, a drug widely-recognized to be cardiotoxic; duloxetine raises adrenergic activity, which potentially increases the risk of myocardial infarction. Pregabalin causes significant fluid retention, and thus can exacerbate heart failure. Consequently, there is an immense need to define these drugs’ risks, specifically serious cardiovascular outcomes resulting in hospitalization or death. We propose to study Medicare Part D beneficiaries because their increased risks and multiple comorbidities heighten the potential for cardiovascular side effects. With increasing scrutiny and limitations placed on opioid prescriptions (one in three beneficiaries received at least one opioid prescription in 2016), the number of Medicare beneficiaries filling prescriptions for these non-opioid drugs—already in the millions—is likely to increase, despite the lack of high quality long-term safety data. We will use state of the art pharmacoepidemiologic techniques and a large database of Medicare enrollees to assemble a cohort of patients with chronic non-cancer pain. Aim 1 will define the risk for serious cardiovascular outcomes in patients taking cyclobenzaprine. Aim 2 will define the risk of serious cardiovascular events associated with the use of duloxetine. Aim 3 will define the risk of heart failure associated with patients taking pregabalin. These studies will compare those risks with the risk observed in patients with chronic pain taking gabapentin, an anticonvulsant with no clinical signals of cardiovascular side effects.

项目摘要 临床医生，患者和研究人员在治疗慢性疼痛方面遇到了许多挑战 有效，安全。慢性疼痛影响3个美国人中约1个，成本高达6350亿美元 治疗的一年和生产力降低；阿片类药物的过量处方已升级为危机。非- 阿片类止痛药是用于疼痛管理的另一种治疗方法；但是，这些数据 药物仅限于缺乏适当评估安全结果的能力的临床研究。 尽管临床试验在建立治疗效率方面起着至关重要的作用，但许多药物都无法预料 和严重的长期副作用。药物电子研究提供了研究这些风险的机会， 特别是在临床试验中经常排除的弱势群体中。我们提出了三项此类研究 旨在提供有关与三种广泛使用相关的心血管风险的关键信息 开处方的非阿片类药物用于治疗慢性疼痛患者：环苯二氮蛋白（肌肉松弛剂）， Duloxetine（5-羟色胺 - 肾上腺素再摄取抑制剂）和gababalin（镇痛抗惊厥药）。我们选择了 这些药物的出于以下原因：1）数百万患者使用它们； 2）多个病例报告提出 担心严重心血管事件的风险增加； 3）他们的行动机制引起了重大 对心血管毒性的关注。更具体地说，环苯二氮一种在结构上与阿米替林相似 药物广泛认可为心脏毒性；杜洛西汀提高了肾上腺素活性，这可能会增加 心肌梗塞的风险。 gababalin会导致明显的液体保留率，因此会加剧心力衰竭。 因此，非常需要定义这些药物的风险，特别是严重的心血管 结果导致住院或死亡。 我们建议研究Medicare D部分受益人，因为他们的风险增加和多种合并症 增强了心血管副作用的潜力。随着对阿片类药物的审查和限制的增加 处方（三分之一的受益人在2016年接受了至少一份阿片类药物处方），数量 医疗保险受益人填补这些非阿片类药物的处方（已经在数百万中已经准备就绪） 增加，dospite缺乏高质量的长期安全数据。 我们将使用ART PharmacoAcooepidemiologic技术和大量的Medicare数据库注册 组装一群患有慢性非癌症疼痛的患者。 AIM 1将定义严重心血管的风险 服用环苯二磷脂的患者的结果。 AIM 2将定义严重心血管事件的风险 与使用杜洛西汀有关。 AIM 3将定义与患者相关的心力衰竭的风险 pregabalin。这些研究将将这些风险与患有慢性疼痛患者观察到的风险进行比较 加巴喷丁是一种抗惊厥药，没有心血管副作用的临床信号。