PCSK9 Inhibition after Heart Transplantation

心脏移植后 PCSK9 抑制

• 批准号: 10617265
• 负责人: WILLIAM F FEARON
• 金额: $ 38.87万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10617265
• 关键词: Adverse event; Anatomy; Anterior Descending Coronary Artery; Anti-Inflammatory Agents; Apolipoproteins B; Arterial Fatty Streak; Arteries; Biological Assay; Biological Markers; Blood Vessels; C-reactive protein; Cause of Death; Cholesterol; Clinical; Complication; Coronary; Coronary Angiography; Coronary Arteriosclerosis; Data; Development; Double-Blind Method; Double-blind trial; Dyslipidemias; Early identification; Endothelium; Goals; Health; Heart Transplantation; Heart failure; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Individual; Inflammation; Investigation; LDL Cholesterol Lipoproteins; Left; Lipids; Lipoprotein (a); Lipoproteins; Measurement; Measures; Mediating; Medical; Methods; Morbidity - disease rate; Outcome; Patients; Pharmaceutical Preparations; Physiological; Physiology; Placebos; Population; Predictive Value; Proprotein Convertases; Randomized; Resistance; Risk; Role; Safety; Subtilisins; Technical Expertise; Techniques; Testing; Therapeutic immunosuppression; Transplant Recipients; Transplantation; Triglycerides; Vascular Diseases; Vascular blood supply; adverse event risk; adverse outcome; coronary plaque; endothelial dysfunction; evidence base; heart allograft; high risk; high risk population; improved; indexing; inflammatory marker; inhibitor; mortality; novel; novel strategies; pleiotropism; pressure; prevent; primary endpoint; prospective; secondary endpoint; treatment and outcome; treatment strategy; ultrasound

Project Summary/Abstract: Cardiac transplantation is the ultimate treatment option for patients with end stage heart failure. Cardiac allograft vasculopathy remains a leading cause of morbidity and mortality after transplantation. Dyslipidemia is a major contributor to cardiac allograft vasculopathy and is suboptimally controlled with current medications. The PCSK9 inhibitors are novel lipid lowering agents which have been shown to significantly lower cholesterol levels and lead to coronary plaque regression in non-transplant individuals. This class of medication has not been tested in cardiac transplant recipients. The objective of this project is to investigate the safety and efficacy of the PCSK9 inhibitor, alirocumab in preventing the development of cardiac allograft vasculopathy. During the first month after cardiac transplantation subjects will undergo coronary angiography with intravascular ultrasound measurements of plaque, vessel and lumen volumes in the left anterior descending coronary artery. Using a coronary pressure wire, epicardial artery and microvascular physiology will be assessed. Finally, endothelial function will be assayed. Subjects will then be randomized in a double blind fashion to either alirocumab or placebo. Baseline and serial lipid values and inflammatory markers will be measured. After 1 year, the above assessment will be repeated. The primary endpoint is the change in plaque volume based on intravascular ultrasound assessment. Secondary endpoints will be the effect of alirocumab on coronary physiology, endothelial function and inflammatory markers. An important secondary aim of this project is to investigate the role of coronary physiology and endothelial function assessment for predicting cardiac allograft vasculopathy, independent of intravascular ultrasound findings. We believe this project will contribute significantly to the evidence base for an important health matter, namely the optimal medical treatment of cardiac transplant recipients.

项目摘要/摘要： 心脏移植是终末期心力衰竭患者的最终治疗选择。 心脏同种异体移植血管病变仍然是移植后发病和死亡的主要原因。 血脂异常是心脏同种异体移植血管病变的一个主要原因，目前的控制效果不佳。 药物。 PCSK9抑制剂是新型降脂剂，已被证明可以显着 降低胆固醇水平并导致非移植个体的冠状动脉斑块消退。这一类的 药物尚未在心脏移植受者中进行测试。该项目的目的是调查 PCSK9 抑制剂 alirocumab 在预防心脏同种异体移植物发展方面的安全性和有效性 血管病变。心脏移植后的第一个月，受试者将接受冠状动脉造影 通过血管内超声测量左前壁的斑块、血管和管腔体积 冠状动脉降支。使用冠状动脉压力丝、心外膜动脉和微血管生理学 将被评估。最后，将测定内皮功能。然后受试者将被随机分为双组 盲目选择 alirocumab 或安慰剂。基线和系列血脂值以及炎症标志物将 测量。 1年后，重复上述评估。主要终点是变化 基于血管内超声评估的斑块体积。次要终点将是以下因素的影响 alirocumab 对冠状动脉生理学、内皮功能和炎症标志物的影响。重要的次要 该项目的目的是研究冠状动脉生理学和内皮功能评估的作用 预测心脏同种异体移植血管病变，独立于血管内超声检查结果。我们相信这一点 该项目将为重要健康问题的证据基础做出重大贡献，即最佳 心脏移植受者的医疗。