Comparative Safety of Pain Medications

止痛药的比较安全性

• 批准号: 10152360
• 负责人: Cecilia Pilar Chung
• 金额: $ 45.62万
• 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/10152360
• 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 safety; 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的努力中遇到了许多挑战 有效和安全。慢性疼痛影响大约三分之一的美国人，每年花费高达6350亿美元。 治疗时间长达一年，丧失了生产力;过量的类阿片处方已升级为危机。非 阿片类止痛药是疼痛管理的一种替代治疗方法;然而，这些数据 药物仅限于临床研究，缺乏适当评估安全性结果的能力。 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，但许多药物都有不可预见的风险。 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。我们提出了三个这样的研究 旨在提供有关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（阿托宁-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 这些药物的原因如下：1）它们被数百万患者使用; 2）多个病例报告提高了 对严重心血管事件风险增加的担忧;和3）其作用机制显著提高 心血管毒性的担忧。更具体地，环苯扎林在结构上类似于阿米替林， 药物被广泛认为是心脏毒性;度洛沙汀提高肾上腺素能活性，这可能会增加 心肌梗死的风险。普瑞巴林会导致严重的液体潴留，从而加重心力衰竭。 因此，非常需要确定这些药物的风险，特别是严重的心血管疾病风险。 导致住院或死亡的结局。 我们建议研究医疗保险D部分受益人，因为他们的风险增加和多种合并症 增加心血管副作用的可能性随着对阿片类药物越来越多的审查和限制， 处方（三分之一的受益人在2016年至少接受过一次阿片类药物处方）， 医疗保险受益人填写这些非阿片类药物的处方-已经有数百万人-很可能 尽管缺乏高质量的长期安全性数据，但这一数字仍在增加。 我们将使用最先进的药物流行病学技术和大型医疗保险注册者数据库， 召集一组慢性非癌症疼痛患者。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局。目标2将定义严重心血管事件的风险 与使用度洛西汀有关目标3将定义与服用以下药物的患者相关的心力衰竭风险： 普瑞巴林这些研究将比较这些风险与慢性疼痛患者的风险 加巴喷丁，一种抗惊厥药，没有心血管副作用的临床信号。