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: 7928914
• 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 2014-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7928914
• 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 强化降脂方案（PREMIER） 摘要 心血管事件的复发率在经历急性心血管事件的患者中高得不可接受。 冠状动脉综合征（ACS）。使用他汀类药物降低血脂水平是治疗高脂血症的基本部分。 这些病人。然而，即使是最密集的药物降脂治疗，虽然证明 上级于标准剂量方案，仍然与不可接受的高CV事件复发率相关。 动脉粥样硬化易损斑块（VP）富脂坏死核心（NC）成分的进展或破裂 导致大多数复发性CV事件。内皮祖细胞（EPC）的血管愈合在血管修复中起着重要作用。 在缺血性损伤后的修复中起关键作用，主要是通过（VP）的内皮化和（VP）的新血管形成。 缺血心肌事实上，在他汀类药物治疗时，EPC动员已被证明可以增强冠状动脉粥样硬化性心脏病的发生。 稳定型冠状动脉疾病（CAD）患者的血流量，并减少心肌缺血和CV ACS患者在治疗的几周内发生的事件。这促使人们不断努力， 降低总胆固醇，特别是低密度脂蛋白（LDL）。然而，仍然存在的是 目前尚不确定的是，最密集的LDL降低治疗（ILLT）与LDL-单采是否会导致快速 VP动脉粥样硬化体积可检测到减少，沿着更强的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 随机分配至初始LDL单采术和口服每日剂量20 mg阿托伐他汀（ILLT组）或 标准他汀类药物单药治疗（SMT），每日剂量高达40 mg阿托伐他汀，无LDL单采。 患者将接受血管内超声和虚拟组织学（IVUS-VH），以确定ILLT是否 在12周时减少靶冠状动脉中的总粥样硬化体积和%NC。细胞培养和流动- 将使用流式细胞仪（FACS）分析来确定EPC-集落形成是否有更大的增加 与SMT组相比，从基线至治疗后4周和12周，外周血EPC-CFU/ml PCI。该研究还将寻找在12周和治疗结束时主要不良CV事件（MACE）的减少。 研究（至少6个月随访）。 如果成功，该试验将提供证据表明，在ACS患者中，ILLT联合LDL-单采术加他汀类药物 治疗将显著减少易损斑块的总粥样硬化体积， 外周循环EPC-CFU/ml，与基于指南的标准他汀类药物单药治疗（SMT）相比 1