The REVEAL study

REVEAL 研究

• 批准号: 8552344
• 负责人: Edward Lakatta
• 金额: $ 4.99万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8552344
• 关键词: Acute; Acute myocardial infarction; Animal Model; Apoptosis; CD34 gene; Cardiac; Cardiovascular system; Cause of Death; Cell Count; Cells; Cessation of life; Confidence Intervals; Cryopreservation; Dose; Double-Blind Method; Enrollment; Epoetin Alfa; Erythropoietin; Event; Experimental Models; Hour; Infarction; Injury; Intervention; Intravenous; Intravenous Bolus; Ischemia; Left Ventricular Function; Left Ventricular Mass; Left Ventricular Remodeling; Magnetic Resonance; Magnetic Resonance Imaging; Measures; Methods; Mononuclear; Morbidity - disease rate; Multicenter Trials; Myocardial Infarction; Outcome; Outcome Measure; Participant; Patients; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Process; Randomized; Reperfusion Therapy; Safety; Saline; Sampling; Scanning; Site; Stem cells; Stents; Stroke; Subgroup; Thrombosis; Time; Ventricular Remodeling; aged; aldehyde dehydrogenases; cohort; design; follow-up; improved; indexing; mortality; neovascularization; older patient; percutaneous coronary intervention; prospective; trend

Context: Acute ST-segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality. In experimental models of MI, erythropoietin reduces infarct size and improves left ventricular (LV) function. Objective: To evaluate the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with STEMI. Design, Setting, and Patients: A prospective, randomized, double-blind, placebocontrolled trial with a dose-escalation safety phase and a single dose (60 000 U of epoetin alfa) efficacy phase; the Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction (REVEAL) trial was conducted at 28 US sites between October 2006 and February 2010, and included 222 patients with STEMI who underwent successful percutaneous coronary intervention (PCI) as a primary or rescue reperfusion strategy. Intervention: Participants were randomly assigned to treatment with intravenous epoetin alfa or matching saline placebo administered within 4 hours of reperfusion. Main Outcome Measure: Infarct size, expressed as percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging performed 2 to 6 days after study medication administration (first CMR) and again 122 weeks later (second CMR). Results In the efficacy cohort, the infarct size did not differ between groups on either the first CMR scan (n=136; 15.8% LV mass 95% confidence interval CI, 13.3- 18.2% LV mass for the epoetin alfa group vs 15.0% LV mass 95% CI, 12.6-17.3% LV mass for the placebo group; P=.67) or on the second CMR scan (n=124; 10.6% LV mass 95% CI, 8.4-12.8% LV mass vs 10.4% LV mass 95% CI, 8.5-12.3% LV mass, respectively; P=.89). In a prespecified analysis of patients aged 70 years or older (n=21), the mean infarct size within the first week (first CMR) was larger in the epoetin alfa group (19.9% LV mass; 95% CI, 14.0-25.7% LV mass) than in the placebo group (11.7% LV mass; 95% CI, 7.2-16.1% LV mass) (P=.03). In the safety cohort, of the 125 patients who received epoetin alfa, the composite outcome of death, MI, stroke, or stent thrombosis occurred in 5 (4.0%; 95% CI, 1.31%-9.09%) but in none of the 97 who received placebo (P=.04). Conclusions: In patients withSTEMIwhohad successful reperfusion with primary or rescue PCI, a single intravenous bolus of epoetin alfa within 4 hours of PCI did not reduce infarct size and was associated with higher rates of adverse cardiovascular events. Subgroup analyses raised concerns about an increase in infarct size among older patients. In a follow-up study, we aimed to determine the feasibility of centrally analyzing EPCs levels to assess the relationship between EPC levels, and EPO administration and infarct size. Methods: Mononuclear cells (MNCs) were locally cryopreserved for central processing from samples obtained prior to rescue or primary percutaneous coronary intervention, as well as at 24 h and 48C72 h postintervention, and analyzed for cells expressing CD133, CD34, and aldehyde dehydrogenase activity. Results: Sampling of EPCs was attempted in 163 of 222 enrolled patients. At least one analyzable sample was obtained in 125 patients, and all three time points were available in 83 patients. There were no statistically significant differences in EPC numbers over time or in the absolute EPC levels between EPO- and placebo-treated patients. There was a trend toward a greater increase in EPC levels from 24 h postintervention to 48C72 h postintervention in patients receiving 30 000 U of EPO ( = 0.11 (placebo) vs 0.092 (EPO), p=0.05). EPC numbers at baseline were inversely related to infarct size (p=0.006, r=-0.39). Conclusions: Local whole cell cryopreservation and central EPC analysis is possible. High-dose (30 000 U) EPO may mobilize EPCs at 48C72 h. Baseline EPC levels are inversely associated with infarct size, suggesting that acute EPC mobilization may be a viable strategy to minimize acute injury.

上下文：急性ST段高程心肌梗塞（STEMI）是主要原因 发病率和死亡率。在MI的实验模型中，红细胞生成素减少了梗死 大小和改善左心室（LV）功能。 目的：评估单一静脉注射epoetin的安全性和功效 STEMI患者的阿尔法。 设计，设置和患者：一种前瞻性，随机，双盲，安慰剂控制 具有剂量降低安全阶段和单剂量的试验（60 000 U的Epoetin 阿尔法疗效阶段；梗塞膨胀和心室重塑的减少 大型心肌梗塞（显示）试验后进行红细胞生成素 在2006年10月至2010年2月之间的美国28个站点，包括222名患者 与STEMI接受了成功经皮冠状动脉干预（PCI）为 初级或救援再灌注策略。 干预：将参与者随机分配给静脉内腹膜素治疗 再灌注后4小时内给药的阿尔法或匹配盐安慰剂。 主要结果度量：梗塞大小，表示为LV质量百分比，评估 研究后2至6天进行了心脏磁共振（CMR）成像 药物给药（第一个CMR）和122周后（第二CMR）。 导致疗效队列的结果，两组之间的梗塞大小在任何方面都没有差异 第一个CMR扫描（n = 136; 15.8％LV质量95％置信区间CI，13.3-- Epoetin Alfa组的LV质量为18.2％，lv质量为15.0％95％CI，12.6-17.3％ 安慰剂组的LV质量； p = .67）或第二CMR扫描（n = 124; 10.6％ LV质量95％CI，8.4-12.8％LV质量vs 10.4％LV质量95％CI，8.5-12.3％LV 质量分别； p = .89）。在对70岁或以上的患者的预定分析中 （n = 21），第一周内的平均梗塞大小（第一CMR）在epoetin中更大 Alfa Group（19.9％LV质量； 95％CI，14.0-25.7％LV质量） 组（11.7％LV质量； 95％CI，7.2-16.1％LV质量）（p = .03）。在安全队列中， 在接受Epoetin alfa的125例患者中，死亡的综合结果Mi， 中风或支架血栓形成发生在5（4.0％； 95％CI，1.31％-9.09％）中，但没有 在接受安慰剂的97人中（p = .04）。 结论：在患者中，STEMIWHOHAD成功再灌注与原发性或救援 PCI，在PCI后4小时内的单次静脉注射epoetin alfa没有减少梗塞 大小，与较高的不良心血管事件发生率有关。子组 分析引起了人们对老年患者梗塞大小增加的担忧。 在一项后续研究中，我们旨在确定中央分析EPC水平以评估EPC水平以及EPO给药和梗死大小之间的关系的可行性。 方法：局部冷冻保存单核细胞（MNC），用于从救援或原发性经皮冠状动脉介入干预之前获得的样品，以及两次干预后24小时和48C72 H，并分析了表达CD133，CD34和Aldeydehyde脱氢酶活性的细胞。 结果：在222名入学的患者中，有163名尝试了EPC的抽样。在125例患者中至少获得了一个可分析的样本，所有三个时间点均可在83位患者中获得。随着时间的推移，EPC数量或EPO治疗患者之间的EPC数量没有统计学上的显着差异。在接受EPO的30 000 U（= 0.11（安慰剂）vs 0.092（EPO），P = 0.05）的患者中，干预后24小时的EPC水平从EPC水平升高到48c72 h的趋势趋势。基线时的EPC数与梗塞大小成反比（p = 0.006，r = -0.39）。 结论：可以进行局部全细胞冷冻保存和中央EPC分析。 高剂量（30 000 U）EPO可能在48c72 h时动员EPC。 基线EPC水平与梗塞大小成反比，这表明急性EPC动员可能是最大程度地减少急性损伤的可行策略。