The Effects and Safety of Statins in Patient with Acute Respiratory Distress Syndrome: A Meta-Analysis_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

DongLiang ¹ , LiLang ² , YanJie ¹ , YanZheng ¹ ,  ZhangXiuhong ³

1. Department of Critical Care Medicine, Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, 214023, China;
2. ;
3. ;

Corresponding author：

ZhangXiuhong, Email: 1091807068@qq.com

Keywords：

Statins; Acute respiratory distress syndrome; Effects; Safety; Meta-analysis

DOI：

10.7507/1671-6205.2016133

Video：

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Objective To evaluate the effects and safety of statins in patients with acute respiratory distress syndrome (ARDS). Methods Literatures in English and Chinese concerning randomized controlled trials (RCTs) on statins in ARDS patients were retrieved by electronic and manual search. All related data were extracted. Meta-analysis was conducted using the statistical software RevMan 5.3 on the basis of strict quality evaluation. Results Five RCTs involving 1489 ARDS patients were included, with 709 patients in the statins group and 780 patients in the placebo control group. Compared with the control group, statins did not improve the survival of ARDS patients[risk ratio (RR) 1.01, 95% confidence interval (CI) 0.86 to 1.18, P=0.91), while the improvement of oxygenation[mean difference (MD) 3.92, 95%CI-14.10 to 21.94, P=0.67], ventilator-free days (MD 0.65, 95%CI-0.20 to 1.50, P=0.13) and non-pulmonary organ failure-free days (MD 1.20, 95%CI-1.46 to 3.87, P=0.38) exhibited no differences between the statins group and the control group. However statins were associated with significant elevation of creatine kinase (MD 6.92, 95%CI 5.77 to 8.07, P < 0.000 01). Conclusion This study demonstrates that statins can not improve outcomes of ARDS patients, and the safety of statins still needs further evaluation.

Citation： DongLiang, LiLang, YanJie, YanZheng, ZhangXiuhong. The Effects and Safety of Statins in Patient with Acute Respiratory Distress Syndrome: A Meta-Analysis. Chinese Journal of Respiratory and Critical Care Medicine, 2016, 15(6): 583-588. doi: 10.7507/1671-6205.2016133 Copy

1.	Ranieri V, Rubenfeld GD, Thompson B, et al. Acute respiratory distress syndrome:the Berlin Definition. JAMA, 2012, 307:2526-2533.
2.	Villar J, Sulemanji D, Kacmarek RM, et al. The acute respiratory distress syndrome:incidence and mortality, has it changed? Curr Opin Crit Care, 2014, 20:3-9.
3.	Pirat A, Zeyneloglu P, Aldemir D, et al. Pretreatment with simvastatin reduces lung injury related to intestinal ischemia-reperfusion in rats. Anesth Analg, 2006, 102:225-232.
4.	Jacobson JR, Barnard JW, Grigoryev DN, et al. Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury. Am J Physiol Lung Cell Mol Physiol, 2005, 288:L1026-1032.
5.	Yao HW, Mao LG, Zhu JP. Protective effects of pravastatin in murine lipopolysaccharide-induced acute lung injury. Clin Exp Pharmacol Physiol, 2006, 33:793-797.
6.	Craig TR, Duffy MJ, Shyamsundar M, et al. A randomized clinical trial of hydroxymethylglutaryl-coenzyme a reductase inhibition for acute lung injury (The HARP Study). Am J Respir Crit Care Med, 2011, 183:620-626.
7.	Truwit JD, Bernard GR, Steingrub J, et al. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med, 2014, 370:2191-2200.
8.	McAuley DF, Laffey JG, O'Kane CM, et al. Simvastatin in the acute respiratory distress syndrome. N Engl J Med, 2014, 371:1695-1703.
9.	Shyamsundar M, McAuley DF, Shields MO, et al. Effect of simvastatin on physiological and biological outcomes in patients undergoing esophagectomy:a randomized placebo-controlled trial. Ann Surg, 2014, 259:26-31.
10.	Mansur A, Steinau M, Popov AF, et al. Impact of statin therapy on mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS) depends on ARDS severity. BMC Med, 2015, 13:128.
11.	Furlan AD, Pennick V, Bombardier C, et al. 2009 updated method guidelines for systematic reviews in the Cochrane Back Review Group. Spine, 2009, 34:1929-1941.
12.	Bein T, Grasso S, Moerer O, et al. The standard of care of patients with ARDS:ventilatory settings and rescue therapies for refractory hypoxemia. Intensive Care Med, 2016, 42:699-711.
13.	董亮, 邱海波.急性肺损伤的治疗进展.中华急诊医学杂志, 2012, 21:235-238.
14.	Cepkova M, Matthay MA. Pharmacotherapy of acute lung injury and the acute respiratory distress syndrome. J Intensive Care Med, 2006, 21:119-143.
15.	Calfee CS, Matthay MA. Nonventilatory treatments for acute lung injury and ARDS. Chest, 2007, 131:913-920.
16.	Yadav H, Lingineni RK, Slivinski EJ, et al. Preoperative statin administration does not protect against early postoperative acute respiratory distress syndrome:a retrospective cohort study. Anesth Analg, 2014, 119:891-898.
17.	Kor DJ, Iscimen R, Yilmaz M, et al. Statin administration did not influence the progression of lung injury or associated organ failures in a cohort of patients with acute lung injury. Intensive Care Med, 2009, 35:1039-1046.
18.	Dinglas VD, Hopkins RO, Wozniak AW, et al. One-year outcomes of rosuvastatin versus placebo in sepsis-associated acute respiratory distress syndrome:prospective follow-up of SAILS randomised trial. Thorax, 2016, 71:401-410.
19.	Grimaldi D, Durand A, Gleeson J, et al. Failure of statins in ARDS:the quest for the "Holy Grail" continues. Minerva Anestesiol, 2016.[Epub ahead of print].
20.	Fernandes V, Santos MJ, Pérez A. Statin-related myotoxicity. Endocrinol Nutr, 2016, 63:239-249.

1. Ranieri V, Rubenfeld GD, Thompson B, et al. Acute respiratory distress syndrome:the Berlin Definition. JAMA, 2012, 307:2526-2533.
2. Villar J, Sulemanji D, Kacmarek RM, et al. The acute respiratory distress syndrome:incidence and mortality, has it changed? Curr Opin Crit Care, 2014, 20:3-9.
3. Pirat A, Zeyneloglu P, Aldemir D, et al. Pretreatment with simvastatin reduces lung injury related to intestinal ischemia-reperfusion in rats. Anesth Analg, 2006, 102:225-232.
4. Jacobson JR, Barnard JW, Grigoryev DN, et al. Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury. Am J Physiol Lung Cell Mol Physiol, 2005, 288:L1026-1032.
5. Yao HW, Mao LG, Zhu JP. Protective effects of pravastatin in murine lipopolysaccharide-induced acute lung injury. Clin Exp Pharmacol Physiol, 2006, 33:793-797.
6. Craig TR, Duffy MJ, Shyamsundar M, et al. A randomized clinical trial of hydroxymethylglutaryl-coenzyme a reductase inhibition for acute lung injury (The HARP Study). Am J Respir Crit Care Med, 2011, 183:620-626.
7. Truwit JD, Bernard GR, Steingrub J, et al. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med, 2014, 370:2191-2200.
8. McAuley DF, Laffey JG, O'Kane CM, et al. Simvastatin in the acute respiratory distress syndrome. N Engl J Med, 2014, 371:1695-1703.
9. Shyamsundar M, McAuley DF, Shields MO, et al. Effect of simvastatin on physiological and biological outcomes in patients undergoing esophagectomy:a randomized placebo-controlled trial. Ann Surg, 2014, 259:26-31.
10. Mansur A, Steinau M, Popov AF, et al. Impact of statin therapy on mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS) depends on ARDS severity. BMC Med, 2015, 13:128.
11. Furlan AD, Pennick V, Bombardier C, et al. 2009 updated method guidelines for systematic reviews in the Cochrane Back Review Group. Spine, 2009, 34:1929-1941.
12. Bein T, Grasso S, Moerer O, et al. The standard of care of patients with ARDS:ventilatory settings and rescue therapies for refractory hypoxemia. Intensive Care Med, 2016, 42:699-711.
13. 董亮, 邱海波.急性肺损伤的治疗进展.中华急诊医学杂志, 2012, 21:235-238.
14. Cepkova M, Matthay MA. Pharmacotherapy of acute lung injury and the acute respiratory distress syndrome. J Intensive Care Med, 2006, 21:119-143.
15. Calfee CS, Matthay MA. Nonventilatory treatments for acute lung injury and ARDS. Chest, 2007, 131:913-920.
16. Yadav H, Lingineni RK, Slivinski EJ, et al. Preoperative statin administration does not protect against early postoperative acute respiratory distress syndrome:a retrospective cohort study. Anesth Analg, 2014, 119:891-898.
17. Kor DJ, Iscimen R, Yilmaz M, et al. Statin administration did not influence the progression of lung injury or associated organ failures in a cohort of patients with acute lung injury. Intensive Care Med, 2009, 35:1039-1046.
18. Dinglas VD, Hopkins RO, Wozniak AW, et al. One-year outcomes of rosuvastatin versus placebo in sepsis-associated acute respiratory distress syndrome:prospective follow-up of SAILS randomised trial. Thorax, 2016, 71:401-410.
19. Grimaldi D, Durand A, Gleeson J, et al. Failure of statins in ARDS:the quest for the "Holy Grail" continues. Minerva Anestesiol, 2016.[Epub ahead of print].
20. Fernandes V, Santos MJ, Pérez A. Statin-related myotoxicity. Endocrinol Nutr, 2016, 63:239-249.

Chinese Journal of Respiratory and Critical Care Medicine

The Effects and Safety of Statins in Patient with Acute Respiratory Distress Syndrome: A Meta-Analysis

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