Plaque Regression and Progenitor Cell Mobilization with Intensive Lipid Eliminati

通过强化脂质消除实现斑块消退和祖细胞动员

• 批准号: 8586861
• 负责人: Subhash Banerjee
• 金额: --
• 依托单位: VA NORTH TEXAS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8586861
• 关键词: Arterial Fatty Streak; Blood; Blood Component Removal; Blood Vessels; Blood flow; Cardiovascular system; Cell Culture Techniques; Cholesterol; Colony-forming units; Coronary; Coronary Arteriosclerosis; Coronary artery; Dose; Elements; Enrollment; Ethical Issues; Event; Excision; Guidelines; Healed; Histology; Injury; Lead; Lipids; Low-Density Lipoproteins; Medical; Myocardial Infarction; Myocardial Ischemia; Natural regeneration; Necrosis; Oral; Patients; Pharmaceutical Preparations; Physicians; Play; Randomized; Randomized Clinical Trials; Recurrence; Regimen; Role; Rupture; Stem cells; Stents; Testing; Time; Ultrasonography; Veterans; abstracting; acute coronary syndrome; atorvastatin; base; density; design; experience; follow-up; healing; high risk; neovascularization; novel; percutaneous coronary intervention; peripheral blood; repaired; stem cell therapy; virtual

Plaque Regression and Progenitor Cell Mobilization with Intensive Lipid Elimination Regimen (PREMIER) Abstract The rate of recurrent cardiovascular events is unacceptably high in patients who experience acute coronary syndrome (ACS). The use of statins to lower lipid levels is a fundamental part of the treatment of these patients. However, even the most intensive pharmacologic lipid lowering therapy, though proven superior to standard dose regimens, is still associated with an unacceptably high rate of recurrent CV events. Progression or rupture of lipid rich necrotic core (NC) elements of atherosclerotic vulnerable plaque (VP) leads to a majority of recurrent CV events. Vascular healing by endothelial progenitor cells (EPC) plays a crucial role in repair following ischemic injury primarily by endothelialization of (VP) and neovascularization of ischemic myocardium. In fact, EPC mobilization while on statin therapy has been shown to enhance coronary blood flow in patients with stable coronary artery disease (CAD), and reduce myocardial ischemia and CV events in patients with ACS within a few weeks of treatment. This has prompted a continuous drive towards lowering of total cholesterol and specifically low-density lipoprotein (LDL). However, what still remains uncertain is whether the most intensive LDL-lowering therapy (ILLT) with LDL-apheresis could lead to a rapid and detectable reduction in VP atheroma volume, along with a more robust EPC mobilization compared to standard statin therapy in ACS patients. In this multi-center trial 114 ACS patients undergoing percutaneous coronary intervention (PCI) will be randomized to either initial LDL-apheresis and an oral daily dose of 20mg of Atorvastatin (ILLT group) or to standard statin monotherapy (SMT) with daily dose of up to 40mg of Atorvastatin without LDL-apheresis. Patients will undergo intravascular ultrasound with virtual histology (IVUS-VH) to determine whether ILLT reduces total atheroma volume and %NC in the target coronary artery at 12 weeks. Cell culture and flow- cytometer (FACS) analysis will be used to determine if there is a greater increase in EPC- colony forming units (EPC-CFU/ml), of peripheral blood, compared to SMT group from baseline to four and 12 weeks post- PCI. The study will also look for a reduction in major adverse CV events (MACE) at 12 weeks and at end of study (at least six months follow-up). If successful, this trial will provide evidence that in ACS patients, ILLT with LDL-apheresis plus statin therapy will significantly reduce the total atheroma volume of vulnerable plaque and augment mobilization of peripherally circulating EPC-CFU/ml, compared to guideline based standard statin monotherapy alone (SMT) 1

斑块消退和祖细胞动员 强化除脂疗法（PREMIER） 抽象的 在经历急性发作的患者中，心血管事件的复发率高得令人难以接受。 冠状动脉综合征（ACS）。使用他汀类药物降低血脂水平是治疗的基本组成部分 这些病人。然而，即使是最强化的药物降脂治疗，尽管已被证明 优于标准剂量方案，但仍与令人无法接受的高复发性心血管事件发生率相关。 动脉粥样硬化易损斑块 (VP) 富含脂质的坏死核心 (NC) 成分的进展或破裂 导致大多数复发性心血管事件。内皮祖细胞 (EPC) 在血管愈合中发挥着重要作用 主要通过内皮化 (VP) 和新生血管形成在缺血性损伤后的修复中发挥关键作用 心肌缺血。事实上，在他汀类药物治疗期间 EPC 动员已被证明可以增强冠状动脉 稳定性冠状动脉疾病 (CAD) 患者的血流量，并减少心肌缺血和心血管病 ACS 患者在治疗几周内发生的事件。这促使人们不断推动 降低总胆固醇，特别是低密度脂蛋白（LDL）。然而，还剩下什么 不确定的是，最强化的 LDL 降低治疗 (ILLT) 结合 LDL 分离术是否可以导致快速 与相比，VP 粥样斑块体积可检测到的减少，以及更强大的 EPC 动员 ACS 患者的标准他汀类药物治疗。 在这项多中心试验中，114 名接受经皮冠状动脉介入治疗 (PCI) 的 ACS 患者将 随机接受初始 LDL 分离术和每日口服 20 毫克阿托伐他汀（ILLT 组）或 标准他汀类药物单一疗法 (SMT)，每日剂量高达 40 毫克阿托伐他汀，无需 LDL 血浆分离术。 患者将接受血管内超声与虚拟组织学 (IVUS-VH) 以确定是否发生 ILLT 12 周时减少目标冠状动脉中的总粥样斑块体积和 %NC。细胞培养和流动- 流式细胞仪 (FACS) 分析将用于确定 EPC 集落形成是否有更大的增加 与 SMT 组相比，从基线到术后 4 周和 12 周，外周血单位 (EPC-CFU/ml) PCI。该研究还将寻找第 12 周和治疗结束时主要不良心血管事件 (MACE) 的减少情况。 研究（至少六个月的随访）。 如果成功，该试验将提供证据表明，在 ACS 患者中，采用 LDL 分离术加他汀类药物进行 ILLT 治疗将显着减少易损斑块的总粥样斑块体积并增强动脉粥样硬化斑块的动员 与基于指南的标准他汀类单药治疗 (SMT) 相比，外周循环 EPC-CFU/ml 1