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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：
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
项目类别：
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

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.

项目总结