Cardiology Division, Faculty of Medical Sciences, State University of Campinas, 13084-971, Campinas, Sao Paulo, Brazil.
Arterioscler Thromb Vasc Biol. 2011 May;31(5):1240-6. doi: 10.1161/ATVBAHA.110.218685. Epub 2011 Mar 3.
Clinical trials of statins during myocardial infarction (MI) have differed in their therapeutic regimes and generated conflicting results. This study evaluated the role of the timing and potency of statin therapy on its potential mechanisms of benefit during MI.
ST-elevation MI patients (n=125) were allocated into 5 groups: no statin; 20, 40, or 80 mg/day simvastatin starting at admission; or 80 mg/day simvastatin 48 hours after admission. After 7 days, all patients switched their treatment to 20 mg/day simvastatin for an additional 3 weeks and then underwent flow-mediated dilation in the brachial artery. As of the second day, C-reactive protein (CRP) differed between non-statin users (12.0±4.1 mg/L) and patients treated with 20 (8.5±4.0 mg/L), 40 (3.8±2.5 mg/L), and 80 mg/day (1.4±1.5 mg/L), and the daily differences remained significant until the seventh day (P<0.0001). The higher the statin dose, the lower the elevation of interleukin-2 and tumor necrosis factor-α, the greater the reduction of 8-isoprostane and low-density lipoprotein(-), and the greater the increase in nitrate/nitrite levels during the first 5 days (P<0.001). Later initiation of statin was less effective than its early introduction in relation to attenuation of CRP, interleukin-2, tumor necrosis factor-α, 8-isoprostane, and low-density lipoprotein(-), as well as in increase in nitrate/nitrite levels (P<0.0001). At the 30th day, there was no longer a difference in lipid profile or CRP between groups; the flow-mediated dilation, however, was proportional to the initial statin dose and was higher for those who started the treatment early (P=0.001).
This study demonstrates that the timing and potency of statin treatment during MI are key elements for their main mechanisms of benefit. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00906451.
心肌梗死（MI）期间的他汀类药物临床试验在治疗方案上存在差异，结果相互矛盾。本研究旨在评估他汀类药物治疗的时机和强度对 MI 潜在获益机制的作用。
将 125 例 ST 段抬高型 MI 患者分为 5 组：未用他汀组；入院时开始给予 20、40 或 80 mg/天辛伐他汀；或入院后 48 小时给予 80 mg/天辛伐他汀。7 天后，所有患者将治疗方案转换为 20 mg/天辛伐他汀，再持续 3 周，然后进行肱动脉血流介导的舒张功能测定。自第 2 天起，与未用他汀的患者（12.0±4.1 mg/L）相比，接受 20、40 和 80 mg/天辛伐他汀治疗的患者的 C 反应蛋白（CRP）分别降低（8.5±4.0 mg/L）、（3.8±2.5 mg/L）和（1.4±1.5 mg/L），且这种差异一直持续到第 7 天（P<0.0001）。他汀类药物剂量越高，白细胞介素-2 和肿瘤坏死因子-α的升高幅度越低，8-异前列烷和低密度脂蛋白（-）的降低幅度越大，前 5 天硝酸盐/亚硝酸盐水平的升高幅度越大（P<0.001）。较晚开始使用他汀类药物与早期使用相比，对 CRP、白细胞介素-2、肿瘤坏死因子-α、8-异前列烷和低密度脂蛋白（-）的抑制作用以及硝酸盐/亚硝酸盐水平的升高作用减弱（P<0.0001）。第 30 天，各组间血脂谱和 CRP 无差异；然而，血流介导的舒张功能与初始他汀类药物剂量呈正相关，且早期开始治疗的患者更高（P=0.001）。
本研究表明，MI 期间他汀类药物治疗的时机和强度是其主要获益机制的关键因素。临床试验注册- URL：http://www.clinicaltrials.gov。唯一标识符：NCT00906451。
