A Randomized Clinical Trial of Hydroxymethylglutaryl-Coenzyme A Reductase Inhibition for Acute Lung Injury (The HARP Study)
A Randomized Clinical Trial of Hydroxymethylglutaryl-Coenzyme A Reductase Inhibition for Acute Lung Injury (The HARP Study)
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DOI：
10.1164/rccm.201003-0423oc
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发表时间：
2011-03-01
影响因子：
24.7
通讯作者：
McAuley, Daniel F.
中科院分区：
文献类型：
--
作者：
Craig, Thelma R.;Duffy, Martin J.;McAuley, Daniel F.
急性肺损伤(ALL)尚无有效的药物治疗方法。他汀类药物是一种潜在的新疗法，因为它们改变了ALI中许多重要的潜在过程。目的：测试辛伐他汀是否改善ALI的生理和生物学结果。方法：我们对所有接受80 mg辛伐他汀或安慰剂治疗的患者进行了随机、双盲、安慰剂对照试验，直到停止机械通气或最多14天。采用热稀释法测定血管外肺水。每天评估肺和非肺器官功能的测量。用支气管肺泡灌洗液和血浆细胞因子评价肺和全身炎症反应。用血浆C反应蛋白测定全身炎症反应。测量和主要结果：纳入60例患者。基线特征，包括人口统计学和疾病严重程度评分，在两组中是相似的。第7天，血管外肺水无明显变化。到第14天，辛伐他汀治疗组的非肺器官功能障碍有所改善。氧合和呼吸力学有所改善，尽管这些参数没有达到统计学意义。两组重症监护病房死亡率均为30%。辛伐他汀耐受性良好，不良反应不增加。辛伐他汀使支气管肺泡灌洗液IL-8减少2.5倍(P=0.04)。结论：辛伐他汀治疗ALI是安全的，可能与改善ALI器官功能障碍有关。这些临床效应可能是通过减少肺部和全身炎症而起作用的。
Rationale There is no effective pharmacological treatment for acute lung injury (All). Statins are a potential new therapy because they modify many of the underlying processes important in ALI.Objectives: To test whether simvastatin improves physiological and biological outcomes in ALI.Methods: We conducted a randomized, double-blinded, placebo-controlled trial in patients with ALL Patients received 80 mg simvastatin or placebo until cessation of mechanical ventilation or up to 14 days. Extravascular lung water was measured using thermodilution. Measures of pulmonary and nonpulmonary organ function were assessed daily. Pulmonary and systemic inflammation was assessed by bronchoalveolar lavage fluid and plasma cytokines. Systemic inflammation was also measured by plasma C-reactive protein.Measurements and Main Results: Sixty patients were recruited. Baseline characteristics, including demographics and severity of illness scores, were similar in both groups. At Day 7, there was no difference in extravascular lung water. By Day 14, the simvastatin-treated group had improvements in nonpulmonary organ dysfunction. Oxygenation and respiratory mechanics improved, although these parameters failed to reach statistical significance. Intensive care unit mortality was 30% in both groups. Simvastatin was well tolerated, with no increase in adverse events. Simvastatin decreased bronchoalveolar lavage IL-8 by 2.5-fold (P = 0.04). Plasma C-reactive protein decreased in both groups but failed to achieve significance in the placebo-treated group.Conclusions: Treatment with simvastatin appears to be safe and may be associated with an improvement in organ dysfunction in ALI. These clinical effects may be mediated by a reduction in pulmonary and systemic inflammation.