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 与一般人群相比，美国退伍军人不成比例地经历疼痛，特别是 剧烈的疼痛。事实上，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）和退伍军人健康管理局（VHA）继续 将注意力集中在慢性疼痛管理上，这导致了新指南的实施， 优先考虑非阿片类药物治疗的系统。 目前阿片类药物治疗慢性疼痛的替代药物包括：（1）局部和口服 镇痛药，如利多卡因、对乙酰氨基酚和非甾体抗炎药（NSAID）;（2） 抗抑郁药;（3）抗惊厥药;和（4）肌肉松弛药。我们和其他人已经定义了心血管 NSAID和阿片类镇痛药的毒性，但用于治疗慢性 疼痛的定义仍然不明确。这对三类药物尤为重要：（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）肌肉松弛药。在每一类毒品中， 度洛沙汀（SNRI）、普瑞巴林（抗癫痫药）和环苯扎林（肌肉松弛剂）是最常用的药物之一。 经常开处方。这三种药物的使用产生了多个病例报告，并提出了具体的 严重心血管事件风险增加的担忧。 目前，每年有数十万退伍军人正在填写这些药物的处方， 非阿片类止痛药的使用正在增加。退伍军人包括具有高心血管风险的脆弱人群 和慢性疼痛的高比率;因此，他们有更高的药物不良反应的风险。绝大多数 的慢性疼痛退伍军人没有癌症或危及生命的疾病，这使得药物的前景 长期使用的毒性是特别重要的考虑因素。 临床试验在证明治疗效果方面发挥着至关重要的作用;然而，许多药物都有不可预见的 和严重的副作用由于临床试验在普遍性方面必然是有限的， 不切实际的药物流行病学研究在我们对长期副作用的认识中起着关键作用， 毒品拟定的药物流行病学研究旨在提供关于 与三种广泛用于治疗慢性疼痛的非阿片类药物相关的心血管风险 并经常开给退伍军人管理局卫生系统的退伍军人。我们将使用最先进的技术和 一个大型的退伍军人数据库，以收集一组慢性非癌症疼痛患者。目标1将定义 服用环苯扎林患者发生严重心血管事件的风险目标2将定义严重风险 与使用度洛昔单抗相关的心血管事件。目标3将定义心力衰竭相关风险 服用普瑞巴林的患者这些研究将比较这些风险与患者中观察到的风险， 慢性疼痛，服用两种活性对照药物：曲马多和塞来昔布。我们的首要目标是改善 退伍军人和防止负面副作用，使这些研究非常适合与退伍军人事务部使命。