Cardiovascular Risk of Non-Opioid Pain Medications

非阿片类止痛药的心血管风险

• 批准号: 10041689
• 负责人: Cecilia Pilar Chung
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10041689
• 关键词: Acetaminophen; Address; Adrenergic Agents; Adverse drug effect; Adverse effects; American; Amitriptyline; Analgesics; Anti-Inflammatory Agents; Anticonvulsants; Antidepressive Agents; Antiepileptic Agents; Arrhythmia; Attention; Awareness; Binding; Blood Pressure; Calcium; Calcium Channel; Cardiomyopathies; Cardiotoxicity; Cardiovascular Diseases; Cardiovascular system; Caring; Case Study; Catecholamines; Cessation of life; Chronic; Clinical Trials; Complex; Congestive Heart Failure; Data; Databases; Drug Controls; Drug Prescriptions; Drug Prospecting; Drug Side Effects; Drug toxicity; Drug usage; European; Event; Exercise; Face; Fibromyalgia; General Population; Goals; Government Agencies; Guidelines; Health; Health system; Heart Arrest; Heart Rate; Heart failure; High Prevalence; Hypotension; Inotropism; Knowledge; Lidocaine; Life; Liquid substance; Long-Term Effects; Longitudinal Studies; Malignant Neoplasms; Manufacturer Name; Medical; Medical Assistance; Medicine; Methods; Mission; Muscle relaxants; Myocardial Infarction; Norepinephrine; Opioid; Opioid Analgesics; Oral; Outcome; Outcome Study; Overdose; Pain; Pain management; Patients; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacology; Play; Population; Recording of previous events; Reporting; Research; Research Personnel; Retrospective cohort study; Risk; Role; Safety; Series; Serotonin; Stress cardiomyopathy; Structure; System; Tachycardia; Techniques; Testing; Time; Toxic effect; Tramadol; Treatment Efficacy; United States; United States Department of Veterans Affairs; United States Food and Drug Administration; Veterans; Veterans Health Administration; Vulnerable Populations; active comparator; active control; attenuation; cardiovascular risk factor; celecoxib; chronic pain; chronic pain management; chronic pain patient; cohort; design; drug mechanism; duloxetine; epidemiology study; experience; high dimensionality; high risk; improved; inhibitor/antagonist; medication safety; midalcipran; military veteran; non-cancer chronic pain; non-opioid analgesic; novel; pregabalin; prevent; reuptake; side effect; study population; voltage

PROJECT SUMMARY When compared to the general population, U.S. Military Veterans disproportionately experience pain, especially severe pain. Indeed, pain management is one of the most common reasons Veterans seek medical assistance. The U.S. Department of Veterans Affairs (VA) and Veterans Health Administration (VHA) have continued to focus attention on chronic pain management, which has resulted in the implementation of new guidelines and systems that prioritize non-opioid treatments. Current pharmacologic alternatives to opioids for chronic pain management include: (1) topical and oral analgesics such as lidocaine, acetaminophen, and non-steroidal anti-inflammatories (NSAIDs); (2) antidepressants; (3) anticonvulsants; and (4) muscle relaxants. We and others have defined the cardiovascular toxicity of NSAIDs and opioid analgesics, but the potential toxicity of other drug classes used to treat chronic pain remains poorly defined. This is particularly important for three classes of drugs: (1) selective norepinephrine reuptake inhibitors (SNRIs) antidepressants, (2) antiepileptics, and (3) muscle relaxants. Within each drug class, duloxetine (SNRI), pregabalin (antiepileptic), and cyclobenzaprine (muscle relaxant) are among the most frequently prescribed. Usage of these three drugs has generated multiple case reports and raised specific concerns for increased risk of serious cardiovascular events. Currently, hundreds of thousands of Veterans are filling prescriptions for these drugs each year, and the use of non-opioid pain drugs is increasing. Veterans encompass a vulnerable population with high cardiovascular risk and high rates of chronic pain; thus, they are at higher risk for adverse drug effects. The overwhelming majority of Veterans with chronic pain do not have cancer or life-threatening illness, which makes the prospect of drug toxicity from long-term use a particularly important consideration. Clinical trials play a crucial role in demonstrating treatments' efficacy; however, many drugs have had unforeseen and serious side effects. Since clinical trials necessarily are limited with regard to generalizability and can be impractical, pharmacoepidemiologic studies play a critical role in our knowledge about the long-term side effects of drugs. The proposed pharmacoepidemiologic studies seek to provide critical information about the cardiovascular risks associated with three widely prescribed non-opioid medications used to treat chronic pain and frequently prescribed to Veterans in the VA health system. We will use state of the art techniques and a large database of Veterans 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 in patients taking pregabalin. These studies will compare those risks with the risk observed in patients with chronic pain taking two active comparators: tramadol and celecoxib. Our overarching goal to improve the health of Veterans and prevent negative side effects makes these studies an excellent fit with the VA mission.

项目摘要 与一般人口相比，美国退伍军人比例过高，尤其是 严重的疼痛。确实，疼痛管理是退伍军人寻求医疗援助的最常见原因之一。 美国退伍军人事务部（VA）和退伍军人卫生管理局（VHA）继续 将注意力集中在慢性疼痛管理上，这导致了新准则的实施 确定非阿片类药物治疗的系统。 慢性疼痛管理阿片类药物的当前药理替代品包括：（1）局部和口服 镇痛药，例如利多卡因，对乙酰氨基酚和非甾体类抗炎（NSAIDS）； （2） 抗抑郁药； （3）抗惊厥药； （4）肌肉放松剂。我们和其他人定义了心血管 NSAIDS和阿片类镇痛药的毒性，但其他用于治疗慢性的药物的潜在毒性 疼痛的定义仍然很差。这对于三类药物尤其重要：（1）选择性去甲肾上腺素 再摄取抑制剂（SNRIS）抗抑郁药，（2）抗癫痫药和（3）肌肉松弛剂。在每个药物类中， Duloxetine（SNRI），前gabalin（抗癫痫症）和环苯二氮蛋白酶（肌肉松弛剂）是最多的 经常处方。这三种药物的使用产生了多个病例报告，并提出了特定的病例报告 担心严重心血管事件的风险增加。 目前，每年数十万退伍军人正在为这些药物填写处方，并使用 非阿片类疼痛药在增加。退伍军人包括高心血管风险的脆弱人群 和高慢性疼痛率；因此，它们面临不良药物影响的较高风险。绝大多数 患有慢性疼痛的退伍军人没有癌症或威胁生命的疾病，这使得毒品的前景 长期使用的毒性特别重要。 临床试验在证明治疗疗效方面起着至关重要的作用。但是，许多药物都无法预料 和严重的副作用。由于临床试验在概括性方面必然受到限制，并且可以是 不切实际的药物ePIDEMIologic研究在我们关于长期副作用的知识中起着至关重要的作用 毒品。拟议的药物电子研究旨在提供有关该的关键信息 与用于治疗慢性疼痛的三种广泛规定的非阿片类药物相关的心血管风险 并经常向VA卫生系统中的退伍军人开处方。我们将使用最先进的技术和 大量的退伍军人数据库组装了一系列慢性非癌症疼痛患者。 AIM 1将定义 服用环苯二磷脂的患者患心血管结局的风险。 AIM 2将定义严重的风险 与使用杜洛西汀有关的心血管事件。 AIM 3将定义与心力衰竭相关的风险 在服用gababalin的患者中。这些研究将将这些风险与在患者中观察到的风险进行比较 慢性疼痛服用两个主动比较剂：曲马多和塞来昔布。我们改善健康的总体目标 退伍军人和预防负面影响使这些研究非常适合VA任务。