Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University.
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
Circ J. 2018 Mar 23;82(4):1083-1091. doi: 10.1253/circj.CJ-17-0889. Epub 2018 Feb 2.
Erythropoietin (EPO) has antiapoptotic and tissue-protective effects, but previous clinical studies using high-dose EPO have not shown cardioprotective effects, probably because of platelet activation and a lack of knowledge regarding the optimal dose. In contrast, a small pilot study using low-dose EPO has shown improvement in left ventricular function without adverse cardiovascular events.
We performed a multicenter (25 hospitals), prospective, randomized, double-blind, placebo-controlled, dose-finding study to clarify the efficacy and safety of low-dose EPO in patients with ST-segment elevation myocardial infarction (STEMI) under the Evaluation System of Investigational Medical Care of the Ministry of Health, Labor and Welfare of Japan. In total, 198 STEMI patients with low left ventricular ejection fraction (LVEF <50%) were randomly assigned to receive intravenous administration of EPO (6,000 or 12,000 IU) or placebo within 6 h of successful percutaneous coronary intervention. At 6 months, there was no significant dose-response relationship in LVEF improvement among the 3 groups tested (EPO 12,000 IU: 5.4±9.3%, EPO 6,000 IU: 7.3±7.7%, Placebo: 8.1±8.3%, P=0.862). Low-dose EPO also did not improve cardiac function, as evaluated by Tc-MIBI SPECT or NT-proBNP at 6 months and did not increase adverse events.
Administration of low-dose EPO did not improve LVEF at 6 months in STEMI patients (UMIN000005721).
促红细胞生成素（EPO）具有抗凋亡和组织保护作用，但以前使用高剂量 EPO 的临床研究并未显示出心脏保护作用，这可能是由于血小板激活以及对最佳剂量缺乏了解。相比之下，一项使用小剂量 EPO 的小型试点研究显示，左心室功能得到改善，而无不良心血管事件。
我们进行了一项多中心（25 家医院）、前瞻性、随机、双盲、安慰剂对照、剂量发现研究，以明确低剂量 EPO 在日本厚生劳动省医疗调查评价系统下 ST 段抬高型心肌梗死（STEMI）患者中的疗效和安全性。共有 198 例低左心室射血分数（LVEF<50%）的 STEMI 患者在经皮冠状动脉介入治疗成功后 6 小时内随机接受静脉注射 EPO（6000 或 12000 IU）或安慰剂。在 6 个月时，3 组患者的 LVEF 改善均无显著的剂量反应关系（EPO 12000 IU：5.4±9.3%，EPO 6000 IU：7.3±7.7%，安慰剂：8.1±8.3%，P=0.862）。低剂量 EPO 也不能改善 6 个月时的心脏功能，这通过 Tc-MIBI SPECT 或 NT-proBNP 评估，且并未增加不良事件。
在 STEMI 患者中，给予低剂量 EPO 不能改善 6 个月时的 LVEF（UMIN000005721）。
