PCSK9 Inhibition after Heart Transplantation

心脏移植后 PCSK9 抑制

• 批准号: 9899367
• 负责人: WILLIAM F FEARON
• 金额: $ 46.19万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9899367
• 关键词: Adverse event; Anatomy; Anterior Descending Coronary Artery; Anti-Inflammatory Agents; Apolipoproteins B; Arterial Fatty Streak; Arteries; Biological Assay; Biological Markers; C-reactive protein; Cardiac development; 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; Lead; 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; Treatment outcome; Triglycerides; Ultrasonography; Vascular Diseases; Vascular blood supply; adverse event risk; adverse outcome; base; coronary plaque; endothelial dysfunction; evidence base; heart allograft; high risk; high risk population; improved; indexing; inflammatory marker; inhibitor/antagonist; mortality; novel; novel strategies; pleiotropism; pressure; prevent; primary endpoint; prospective; secondary endpoint; treatment strategy

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。 同种异体心脏移植血管病变仍然是移植后发病率和死亡率的主要原因。 血脂异常是心脏移植物血管病变的主要诱因，目前治疗效果不佳。 药物。PCSK9抑制剂是一种新型降脂剂，已被证明具有显著的 降低胆固醇水平，并导致非移植患者的冠状动脉斑块消退。这一类人 药物还没有在心脏移植接受者身上进行测试。这个项目的目标是调查 PCSK9抑制剂alirocumab预防同种异体心脏移植的安全性和有效性 血管病变。在心脏移植后的第一个月内，受试者将接受冠状动脉造影 血管内超声测量左前部斑块、血管和管腔体积 冠状动脉下行。使用冠状动脉压力线、心外膜动脉和微血管生理学 将会被评估。最后对内皮功能进行检测。然后，受试者将被随机分成两组 对阿利鲁单抗或安慰剂的盲目时尚。基线和系列血脂和炎症标志物 量过了。一年后，上述评估将再次进行。主要终点是中的更改 基于血管内超声评估的斑块体积。次要端点的影响将是 阿利洛单抗对冠脉生理、内皮功能和炎症标志物的影响。一个重要的次要角色 本项目的目的是探讨冠状动脉生理学和血管内皮功能评估在 预测同种异体心脏移植血管病变，独立于血管内超声表现。我们相信这一点 该项目将极大地促进一个重要的健康问题的证据基础，即最佳 心脏移植受者的内科治疗。