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Comparative Safety of Pain Medications

止痛药的比较安全性

基本信息

批准号：
10390399
负责人：
Cecilia Pilar Chung
金额：
$ 46.52万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10390399
关键词：
Address Adrenergic Agents Affect American Amitriptyline Analgesics Anticonvulsants Benefits and Risks Binding 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 Sum Techniques Testing Time Toxic effect Treatment Efficacy Treatment outcome United States Food and Drug Administration Vulnerable Populations alternative treatment attenuation beneficiary blood pressure elevation cardiovascular risk factor chronic pain chronic pain management chronic pain patient cohort comorbidity comparative safety cost design drug mechanism duloxetine epidemiology study gabapentin high dimensionality high risk improved inhibitor medication safety non-cancer chronic pain non-opioid analgesic novel pregabalin prescription opioid pressure reuptake safety outcomes side effect voltage

项目摘要

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.

项目概要临床医生、患者和研究人员在治疗慢性疼痛的过程中遇到了许多挑战有效且安全。慢性疼痛影响大约三分之一的美国人，每年造成的损失高达 6,350 亿美元治疗和生产力损失的年数；阿片类药物的过量处方已升级为一场危机。非- 阿片类止痛药是疼痛管理的一种替代治疗方法；然而，关于这些的数据药物仅限于临床研究，缺乏适当评估安全结果的能力。尽管临床试验在确定治疗效果方面发挥着至关重要的作用，但许多药物都出现了不可预见的情况和严重的长期副作用。药物流行病学研究提供了研究这些风险的机会，特别是在经常被排除在临床试验之外的弱势群体中。我们提出三项这样的研究旨在提供有关与广泛使用三种药物相关的心血管风险的关键信息用于治疗慢性疼痛患者的处方非阿片类药物：环苯扎林（肌肉松弛剂），度洛西汀（血清素-去甲肾上腺素再摄取抑制剂）和普瑞巴林（镇痛抗惊厥药）。我们选择了这些药物的原因如下：1）它们被数以百万计的患者使用； 2）多起病例报告引发担心严重心血管事件的风险增加； 3）它们的作用机制引起了显着的担心心血管毒性。更具体地说，环苯扎林在结构上与阿米替林相似，阿米替林是一种被广泛认为具有心脏毒性的药物；度洛西汀会提高肾上腺素能活性，从而可能增加心肌梗塞的风险。普瑞巴林会导致明显的液体潴留，从而加剧心力衰竭。因此，非常需要定义这些药物的风险，特别是严重的心血管风险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且患有多种合并症增加心血管副作用的可能性。随着对阿片类药物的审查和限制越来越多处方（2016 年三分之一的受益人至少收到一种阿片类药物处方）、为这些非阿片类药物配药的医疗保险受益人（已经有数百万）可能会尽管缺乏高质量的长期安全数据，但仍在增加。我们将使用最先进的药物流行病学技术和医疗保险参保者的大型数据库来收集一组患有慢性非癌症疼痛的患者。目标 1 将定义严重心血管疾病的风险服用环苯扎林的患者的结果。目标 2 将定义严重心血管事件的风险与度洛西汀的使用有关。目标 3 将定义与患者服用药物相关的心力衰竭风险普瑞巴林。这些研究将这些风险与慢性疼痛患者观察到的风险进行比较加巴喷丁，一种抗惊厥药，没有心血管副作用的临床信号。