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.

背景：急性 ST 段抬高型心肌梗死 (STEMI) 是一个主要原因 发病率和死亡率。在 MI 实验模型中，促红细胞生成素可减少梗塞 大小并改善左心室（LV）功能。 目的：评价单次静脉推注促红细胞生成素的安全性和有效性 STEMI 患者服用阿尔法。 设计、环境和患者：前瞻性、随机、双盲、安慰剂对照 剂量递增安全阶段和单剂量（60 000 U 促红细胞生成素 alfa)功效期；减少梗塞扩张和心室重塑 进行大面积心肌梗死后促红细胞生成素 (REVEAL) 试验 2006 年 10 月至 2010 年 2 月期间在美国 28 个地点进行，包括 222 名患者 患有 STEMI 并成功接受经皮冠状动脉介入治疗 (PCI) 的患者 主要或救援再灌注策略。 干预：参与者被随机分配接受静脉注射促红细胞生成素治疗 再灌注后 4 小时内给予 alfa 或匹配的生理盐水安慰剂。 主要结果指标：评估梗死面积，以左心室质量的百分比表示 通过研究后 2 至 6 天进行的心脏磁共振 (CMR) 成像 药物给药（第一次 CMR），122 周后再次给药（第二次 CMR）。 结果 在疗效队列中，两组之间的梗死面积没有差异 第一次 CMR 扫描（n=136；15.8% LV 质量 95% 置信区间 CI，13.3- 阿尔法促红细胞生成素组 LV 质量为 18.2% vs LV 质量 15.0% 95% CI, 12.6-17.3% 安慰剂组的 LV 质量； P=.67) 或第二次 CMR 扫描 (n=124; 10.6% 左室质量 95% CI，8.4-12.8% 左室质量 vs 10.4% 左室质量 95% CI，8.5-12.3% 左室 质量，分别； P=.89）。在对 70 岁或以上患者的预先指定分析中 (n=21)，第一周内的平均梗死面积（第一次 CMR）在促红细胞生成素中更大 alfa 组（19.9% LV 质量；95% CI，14.0-25.7% LV 质量）高于安慰剂组 组（11.7% LV 质量；95% CI，7.2-16.1% LV 质量）（P=.03）。在安全队列中， 在接受阿法依泊汀治疗的 125 名患者中，死亡、心肌梗死、 5 例发生中风或支架内血栓（4.0%；95% CI，1.31%-9.09%），但没有发生 97 名接受安慰剂的人中的 (P=.04)。 结论：在初次或抢救成功再灌注的 STEMI 患者中 PCI（PCI 后 4 小时内单次静脉推注阿法红细胞生成素并不能减少梗塞） 大小，并与较高的不良心血管事件发生率相关。子群 分析引起了人们对老年患者梗塞面积增加的担忧。 在后续研究中，我们旨在确定集中分析 EPC 水平以评估 EPC 水平、EPO 给药和梗塞面积之间关系的可行性。 方法：对抢救或初次经皮冠状动脉介入治疗前以及干预后 24 小时和 48°C72 小时获得的样本进行局部冷冻保存，以便进行中央处理，并分析表达 CD133、CD34 和乙醛脱氢酶活性的细胞。 结果：尝试对 222 名入组患者中的 163 名进行 EPC 采样。 125 名患者至少获得了一份可分析样本，83 名患者的所有三个时间点均可用。 EPO 和安慰剂治疗患者之间的 EPC 数量随时间变化或绝对 EPC 水平没有统计学上的显着差异。在接受 30 000 U EPO 的患者中，从干预后 24 小时到干预后 48°C72 小时，EPC 水平有更大增加的趋势（= 0.11（安慰剂）与 0.092（EPO），p=0.05）。基线时的 EPC 数量与梗塞面积呈负相关（p=0.006，r=-0.39）。 结论：局部全细胞冷冻保存和中央 EPC 分析是可能的。 高剂量（30 000 U）EPO可能在48C72小时动员EPC。 基线 EPC 水平与梗塞面积呈负相关，表明急性 EPC 动员可能是最大程度减少急性损伤的可行策略。