Virginia Commonwealth University, VCU Pauley Heart Center, Richmond, Virginia, USA.
Am J Cardiol. 2010 May 15;105(10):1371-1377.e1. doi: 10.1016/j.amjcard.2009.12.059. Epub 2010 Apr 2.
Acute myocardial infarction (AMI) initiates an intense inflammatory response in which interleukin-1 (IL-1) plays a central role. The IL-1 receptor antagonist is a naturally occurring antagonist, and anakinra is the recombinant form used to treat inflammatory diseases. The aim of the present pilot study was to test the safety and effects of IL-1 blockade with anakinra on left ventricular (LV) remodeling after AMI. Ten patients with ST-segment elevation AMI were randomized to either anakinra 100 mg/day subcutaneously for 14 days or placebo in a double-blind fashion. Two cardiac magnetic resonance (CMR) imaging and echocardiographic studies were performed during a 10- to 14-week period. The primary end point was the difference in the interval change in the LV end-systolic volume index (LVESVi) between the 2 groups on CMR imaging. The secondary end points included differences in the interval changes in the LV end-diastolic volume index, and C-reactive protein levels. A +2.0 ml/m(2) median increase (interquartile range +1.0, +11.5) in the LVESVi on CMR imaging was seen in the placebo group and a -3.2 ml/m(2) median decrease (interquartile range -4.5, -1.6) was seen in the anakinra group (p = 0.033). The median difference was 5.2 ml/m(2). On echocardiography, the median difference in the LVESVi change was 13.4 ml/m(2) (p = 0.006). Similar differences were observed in the LV end-diastolic volume index on CMR imaging (7.6 ml/m(2), p = 0.033) and echocardiography (9.4 ml/m(2), p = 0.008). The change in C-reactive protein levels between admission and 72 hours after admission correlated with the change in the LVESVi (R = +0.71, p = 0.022). In conclusion, in the present pilot study of patients with ST-segment elevation AMI, IL-1 blockade with anakinra was safe and favorably affected by LV remodeling. If confirmed in larger trials, IL-1 blockade might represent a novel therapeutic strategy to prevent heart failure after AMI.
急性心肌梗死（AMI）引发强烈的炎症反应，其中白细胞介素-1（IL-1）起着核心作用。IL-1 受体拮抗剂是一种天然存在的拮抗剂，阿那白滞素是用于治疗炎症性疾病的重组形式。本初步研究旨在测试 IL-1 阻断剂阿那白滞素对 AMI 后左心室（LV）重构的安全性和疗效。10 名 ST 段抬高 AMI 患者被随机分为两组，每组皮下注射阿那白滞素 100mg/天，共 14 天，或安慰剂，采用双盲法。在 10-14 周期间进行了两次心脏磁共振（CMR）成像和超声心动图研究。主要终点是两组 CMR 成像上 LV 收缩末期容积指数（LVESVi）的间隔变化差异。次要终点包括 LV 舒张末期容积指数和 C 反应蛋白水平的间隔变化差异。安慰剂组 CMR 成像上 LVESVi 的中位数增加了+2.0ml/m²（四分位距+1.0，+11.5），阿那白滞素组中位数减少了-3.2ml/m²（四分位距-4.5，-1.6）（p=0.033）。中位数差异为 5.2ml/m²。超声心动图上，LVESVi 变化的中位数差异为 13.4ml/m²（p=0.006）。CMR 成像（7.6ml/m²，p=0.033）和超声心动图（9.4ml/m²，p=0.008）上 LV 舒张末期容积指数也观察到类似的差异。入院时和入院后 72 小时时 C 反应蛋白水平的变化与 LVESVi 的变化相关（R=+0.71，p=0.022）。总之，在本初步研究中，ST 段抬高 AMI 患者的 IL-1 阻断剂阿那白滞素是安全的，并对 LV 重构产生有利影响。如果在更大的试验中得到证实，IL-1 阻断可能代表一种预防 AMI 后心力衰竭的新治疗策略。
