Efficacy and safety of simvastatin in the adjunct therapy of chronic obstructive pulmonary disease: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LI Le ^1,2 , YANG Nan ^3,4 , ZHOU Qi ^1,3,4 , LUO Xufei ⁵ ,  YUE Hongmei ^1,2

1. The First Medical School of Lanzhou University, Lanzhou 730000, P.R.China;
2. Department of Respiratory, the First Hospital of Lanzhou University, Lanzhou 730000, P.R.China;
3. Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, P.R.China;
4. Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou 730000, P.R.China;
5. School of Public Health, Lanzhou University, Lanzhou 730000, P.R.China;

Corresponding author：

YUE Hongmei, Email: yuehongmeil8@sina.com

Keywords：

Simvastatin; Chronic obstructive pulmonary disease; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.202006107

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To systematically review the efficacy and safety of simvastatin and its different doses in the adjunct therapy of chronic obstructive pulmonary disease (COPD).Methods PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, WanFang Data, CBM and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on adjunct therapy of simvastatin in patients with COPD from inception to May 15^th, 2020. Two reviewers independently screened literature, extracted data and assessed risk bias of included studies; then, meta-analysis was performed by using Stata 14.0 software.Results A total of 22 RCTs involving 2 377 patients were included. The results of meta-analysis showed that treatment with 20 mg simvastatin could improve FEV₁%pred, FEV₁/FVC, and reduce inflammatory indexes such as CRP, hs-CRP, IL-8 and TNF-α, while 40 mg failed to improve. Simvastatin could reduce COPD score (CAT), but failed to increase the 6-minute walking distance or alleviate acute exacerbation.Conclusions Current evidence shows that treatment with 20 mg simvastatin can improve pulmonary function, reduce inflammatory index and optimize CAT score in COPD patients, but it cannot increase the 6-minute walking distance and reduce the number of acute exacerbations of COPD. Due to the limited quantity and quality of included studies, the above conclusions are needed to be verified by more high-quality studies.

Citation： LI Le, YANG Nan, ZHOU Qi, LUO Xufei, YUE Hongmei. Efficacy and safety of simvastatin in the adjunct therapy of chronic obstructive pulmonary disease: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2021, 21(2): 145-152. doi: 10.7507/1672-2531.202006107 Copy

1.	中国老年医学学会呼吸病学分会慢性阻塞性肺疾病学组. 中国老年慢性阻塞性肺疾病临床诊治实践指南. 中华结核和呼吸杂志, 2020, 43(2): 100-119.
2.	WHO. Causes-of-death. Available at: https://www.who.int/data/gho/data/themes/topics/causes-of-death/GHO/causes-of-death.
3.	Wang C, Xu J, Yang L, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health[CPH] study): a national cross-sectional study. Lancet, 2018, 391(10131): 1706-1717.
4.	Young RP, Hopkins RJ. Update on the potential role of statins in chronic obstructive pulmonary disease and its co-morbidities. Expert Rev Respir Med, 2013, 7(5): 533-544.
5.	Thomson NC. Clinical studies of statins in asthma and COPD. Curr Mol Pharmacol, 2017, 10(1): 60-71.
6.	Lu YB, Chang RX, Yao J, et al. Effectiveness of long-term using statins in COPD-a network meta-analysis. Respir Res, 2019, 20(1): 17.
7.	Walsh A, Perrem L, Khashan AS, et al. Statins versus placebo for people with chronic obstructive pulmonary disease. Cochrane Database Syst Rev, 2019, (7): CD011959.
8.	Vestbo J, Hurd SS, Agusti AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med, 2013, 187(4): 347-365.
9.	中华医学会呼吸病学分会慢性阻塞性肺疾病学组. 慢性阻塞性肺疾病诊治指南(2013年修订版). 中华结核和呼吸杂志, 2013, 36(4): 255-264.
10.	Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions (Version 5.1.0). The Cochrane Collaboration, 2011. Available at: http://www.cochrane-handbook.org.
11.	Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109): 629-634.
12.	金晓洁, 王万铁, 戴新建, 等. COPD稳定期治疗中CAT mMRC与BODE指数的相关性研究及辛伐他汀干预的影响. 数理医药学杂志, 2016, (7): 952-955.
13.	余胜忠, 赵宇, 李元广. 小剂量辛伐他汀对稳定期慢性阻塞性肺疾病患者生活质量的影响. 中国医学创新, 2014, 11(6): 40-41.
14.	王永彬, 王伟. 辛伐他汀对COPD患者细胞凋亡和炎症因子的干预作用. 山东大学学报(医学版), 2009, 47(8): 75-78.
15.	门雪琳, 王永瑞. 辛伐他汀对慢性阻塞性肺病患者缓解期的影响研究. 实用心脑肺血管病杂志, 2011, 19(4): 554-555.
16.	蒋智敏, 历风元, 童旭芳, 等. 辛伐他汀对慢性阻塞性肺疾病肺功能的影响及作用机制研究. 海南医学, 2013, 24(9): 1277-1279.
17.	郭新跃. 辛伐他汀对COPD患者肺功能, 血清IL-17, IL-13及脂联素的影响. 中国现代医生, 2012, 50(26): 61-63.
18.	陈焕珍, 戢秋明, 李兰. 辛伐他汀对老年慢性阻塞性肺疾病患者肺功能、免疫功能及生活质量的影响. 临床肺科杂志, 2016, 21(5): 940-942.
19.	张艳. 辛伐他汀在COPD治疗中的临床应用研究. 中外健康文摘, 2011, 8(47): 250-251.
20.	吕红, 陶政正, 范桂芹, 等. 辛伐他汀治疗慢性阻塞性肺病患者的临床疗效观察. 现代医学, 2017, 45(4): 575-578.
21.	吴轶赟, 廖浪霞. 辛伐他汀治疗慢性阻塞性肺疾病的疗效及其对患者C反应蛋白, 前白蛋白和肺功能的影响. 海南医学, 2016, 27(23): 3807-3810.
22.	金雪梅, 李晓佳. 辛伐他汀治疗慢性阻塞性肺疾病患者疗效观察. 临床肺科杂志, 2011, 16(7): 1012-1014.
23.	江雪慧. 辛伐他汀对慢性阻塞性肺疾病患者血浆炎症因子的影响及疗效观察. 中国药物与临床, 2012, 12(12): 1602-1603.
24.	金晓博. 辛伐他汀对COPD患者诱导痰炎性标志物、肺功能及临床症状的影响研究. 医学信息, 2013, 28: 302-303.
25.	陈代刚, 杜飞. 辛伐他汀对慢性阻塞性肺疾病急性加重期患者血清炎性因子, 肺动脉高压及肺功能的影响. 中国老年学杂志, 2017, 37(14): 3523-3524.
26.	童旭芳, 朱涟敏. 辛伐他汀对慢性阻塞性肺疾病炎症因子的影响. 江西医药, 2015, 50(5): 434-435.
27.	汪国斌. 辛伐他汀治疗AECOPD疗效. 临床肺科杂志, 2014, 19(6): 1018-1020.
28.	Kaczmarek P, Sładek K, Skucha W, et al. The influence of simvastatin on selected inflammatory markers in patients with chronic obstructive pulmonary disease. Pol Arch Med Wewn, 2010, 120(1-2): 11-17.
29.	John ME, Cockcroft JR, McKeever TM, et al. Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a randomized controlled trial. Int J Chron Obstruct Pulmon Dis, 2015, 10: 211-221.
30.	Balaguer C, Peralta A, Riosa, et al. Effects of simvastatin in chronic obstructive pulmonary disease: Results of a pilot, randomized, placebo-controlled clinical trial. Contemp Clin Trials Commun, 2016, 2: 91-96.
31.	Criner GJ, Connett JE, Aaron SD, et al. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med, 2014, 370(23): 2201-2210.
32.	Maneechotesuwan K, Wongkajornsilp A, Adcock IM, et al. Simvastatin suppresses airway IL-17 and upregulates IL-10 in patients with stable COPD. Chest, 2015, 148(5): 1164-1176.
33.	Patyk I, Rybacki C, Kalicka A, et al. Simvastatin therapy and Broncho alveolar lavage fluid biomarkers in chronic obstructive pulmonary disease. Adv Exp Med Biol, 2019, 1150: 43-52.
34.	Wang A, Yu BN, Luo CH, et al. Ile118Val genetic polymorphism of CYP3A4 and its effects on lipid-lowering efficacy of simvastatin in Chinese hyperlipidemia patients. Eur J Clin Pharmacol, 2005, 60(12): 843-848.
35.	Bogman K, Peyer AK, Torok M, et al. HMG-CoA reductase inhibitors and P-glycoprotein modulation. Br J Pharmacol, 2001, 132(6): 1183-1192.
36.	蔡柔荧. 根据临床案例分析中国ACS患者能否耐受高强度他汀治疗. 海峡药学, 2018, 30(9): 240-243.
37.	周颖, 姜红, 王勇. 强化他汀治疗的种族差异—中国人适合强化他汀治疗吗?. 医学综述, 2012, 18(4): 591-593.
38.	Liao JK. Safety and efficacy of statins in Asians. Am J Cardiol, 2007, 99: 410-414.
39.	Zhang W, Zhang Y, Li CW, et al. Effect of statins on chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials. Chest, 2017, 152: 1159-1168.
40.	Barnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol, 2016, 138(1): 16-27.
41.	Amariei DE, Reed RM. The role of statins in chronic obstructive pulmonary disease: is cardiovascular disease the common denominator? Curr Opin Pulm Med, 2019, 25(2): 173-178.
42.	Alexeeff SE, Litonjua AA, Sparrow D, et al. Statin use reduces decline in lung function: VA Normative Aging Study. Am J Respir Crit Care Med, 2007, 176(8): 742-747.
43.	Blamoun AI, Batty GN, Debari VA, et al. Statins may reduce episodes of exacerbation and the requirement for intubation in patients with COPD: evidence from a retrospective cohort study. Int J Clin Pract, 2008, 62(9): 1373-1378.
44.	Ingebrigtsen TS, Marott JL, Nordestgaard BG, et al. Statin use and exacerbations in individuals with chronic obstructive pulmonary disease. Thorax, 2015, 70(1): 33-40.
45.	Lin CM, Yang TM, Yang YH, et al. Statin Use and the Risk of Subsequent Hospitalized Exacerbations in COPD Patients with Frequent Exacerbations. Int J Chron Obstruct Pulmon Dis, 2020, 15: 289-299.

1. 中国老年医学学会呼吸病学分会慢性阻塞性肺疾病学组. 中国老年慢性阻塞性肺疾病临床诊治实践指南. 中华结核和呼吸杂志, 2020, 43(2): 100-119.
2. WHO. Causes-of-death. Available at: https://www.who.int/data/gho/data/themes/topics/causes-of-death/GHO/causes-of-death.
3. Wang C, Xu J, Yang L, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health[CPH] study): a national cross-sectional study. Lancet, 2018, 391(10131): 1706-1717.
4. Young RP, Hopkins RJ. Update on the potential role of statins in chronic obstructive pulmonary disease and its co-morbidities. Expert Rev Respir Med, 2013, 7(5): 533-544.
5. Thomson NC. Clinical studies of statins in asthma and COPD. Curr Mol Pharmacol, 2017, 10(1): 60-71.
6. Lu YB, Chang RX, Yao J, et al. Effectiveness of long-term using statins in COPD-a network meta-analysis. Respir Res, 2019, 20(1): 17.
7. Walsh A, Perrem L, Khashan AS, et al. Statins versus placebo for people with chronic obstructive pulmonary disease. Cochrane Database Syst Rev, 2019, (7): CD011959.
8. Vestbo J, Hurd SS, Agusti AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med, 2013, 187(4): 347-365.
9. 中华医学会呼吸病学分会慢性阻塞性肺疾病学组. 慢性阻塞性肺疾病诊治指南(2013年修订版). 中华结核和呼吸杂志, 2013, 36(4): 255-264.
10. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions (Version 5.1.0). The Cochrane Collaboration, 2011. Available at: http://www.cochrane-handbook.org.
11. Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109): 629-634.
12. 金晓洁, 王万铁, 戴新建, 等. COPD稳定期治疗中CAT mMRC与BODE指数的相关性研究及辛伐他汀干预的影响. 数理医药学杂志, 2016, (7): 952-955.
13. 余胜忠, 赵宇, 李元广. 小剂量辛伐他汀对稳定期慢性阻塞性肺疾病患者生活质量的影响. 中国医学创新, 2014, 11(6): 40-41.
14. 王永彬, 王伟. 辛伐他汀对COPD患者细胞凋亡和炎症因子的干预作用. 山东大学学报(医学版), 2009, 47(8): 75-78.
15. 门雪琳, 王永瑞. 辛伐他汀对慢性阻塞性肺病患者缓解期的影响研究. 实用心脑肺血管病杂志, 2011, 19(4): 554-555.
16. 蒋智敏, 历风元, 童旭芳, 等. 辛伐他汀对慢性阻塞性肺疾病肺功能的影响及作用机制研究. 海南医学, 2013, 24(9): 1277-1279.
17. 郭新跃. 辛伐他汀对COPD患者肺功能, 血清IL-17, IL-13及脂联素的影响. 中国现代医生, 2012, 50(26): 61-63.
18. 陈焕珍, 戢秋明, 李兰. 辛伐他汀对老年慢性阻塞性肺疾病患者肺功能、免疫功能及生活质量的影响. 临床肺科杂志, 2016, 21(5): 940-942.
19. 张艳. 辛伐他汀在COPD治疗中的临床应用研究. 中外健康文摘, 2011, 8(47): 250-251.
20. 吕红, 陶政正, 范桂芹, 等. 辛伐他汀治疗慢性阻塞性肺病患者的临床疗效观察. 现代医学, 2017, 45(4): 575-578.
21. 吴轶赟, 廖浪霞. 辛伐他汀治疗慢性阻塞性肺疾病的疗效及其对患者C反应蛋白, 前白蛋白和肺功能的影响. 海南医学, 2016, 27(23): 3807-3810.
22. 金雪梅, 李晓佳. 辛伐他汀治疗慢性阻塞性肺疾病患者疗效观察. 临床肺科杂志, 2011, 16(7): 1012-1014.
23. 江雪慧. 辛伐他汀对慢性阻塞性肺疾病患者血浆炎症因子的影响及疗效观察. 中国药物与临床, 2012, 12(12): 1602-1603.
24. 金晓博. 辛伐他汀对COPD患者诱导痰炎性标志物、肺功能及临床症状的影响研究. 医学信息, 2013, 28: 302-303.
25. 陈代刚, 杜飞. 辛伐他汀对慢性阻塞性肺疾病急性加重期患者血清炎性因子, 肺动脉高压及肺功能的影响. 中国老年学杂志, 2017, 37(14): 3523-3524.
26. 童旭芳, 朱涟敏. 辛伐他汀对慢性阻塞性肺疾病炎症因子的影响. 江西医药, 2015, 50(5): 434-435.
27. 汪国斌. 辛伐他汀治疗AECOPD疗效. 临床肺科杂志, 2014, 19(6): 1018-1020.
28. Kaczmarek P, Sładek K, Skucha W, et al. The influence of simvastatin on selected inflammatory markers in patients with chronic obstructive pulmonary disease. Pol Arch Med Wewn, 2010, 120(1-2): 11-17.
29. John ME, Cockcroft JR, McKeever TM, et al. Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a randomized controlled trial. Int J Chron Obstruct Pulmon Dis, 2015, 10: 211-221.
30. Balaguer C, Peralta A, Riosa, et al. Effects of simvastatin in chronic obstructive pulmonary disease: Results of a pilot, randomized, placebo-controlled clinical trial. Contemp Clin Trials Commun, 2016, 2: 91-96.
31. Criner GJ, Connett JE, Aaron SD, et al. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med, 2014, 370(23): 2201-2210.
32. Maneechotesuwan K, Wongkajornsilp A, Adcock IM, et al. Simvastatin suppresses airway IL-17 and upregulates IL-10 in patients with stable COPD. Chest, 2015, 148(5): 1164-1176.
33. Patyk I, Rybacki C, Kalicka A, et al. Simvastatin therapy and Broncho alveolar lavage fluid biomarkers in chronic obstructive pulmonary disease. Adv Exp Med Biol, 2019, 1150: 43-52.
34. Wang A, Yu BN, Luo CH, et al. Ile118Val genetic polymorphism of CYP3A4 and its effects on lipid-lowering efficacy of simvastatin in Chinese hyperlipidemia patients. Eur J Clin Pharmacol, 2005, 60(12): 843-848.
35. Bogman K, Peyer AK, Torok M, et al. HMG-CoA reductase inhibitors and P-glycoprotein modulation. Br J Pharmacol, 2001, 132(6): 1183-1192.
36. 蔡柔荧. 根据临床案例分析中国ACS患者能否耐受高强度他汀治疗. 海峡药学, 2018, 30(9): 240-243.
37. 周颖, 姜红, 王勇. 强化他汀治疗的种族差异—中国人适合强化他汀治疗吗?. 医学综述, 2012, 18(4): 591-593.
38. Liao JK. Safety and efficacy of statins in Asians. Am J Cardiol, 2007, 99: 410-414.
39. Zhang W, Zhang Y, Li CW, et al. Effect of statins on chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials. Chest, 2017, 152: 1159-1168.
40. Barnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol, 2016, 138(1): 16-27.
41. Amariei DE, Reed RM. The role of statins in chronic obstructive pulmonary disease: is cardiovascular disease the common denominator? Curr Opin Pulm Med, 2019, 25(2): 173-178.
42. Alexeeff SE, Litonjua AA, Sparrow D, et al. Statin use reduces decline in lung function: VA Normative Aging Study. Am J Respir Crit Care Med, 2007, 176(8): 742-747.
43. Blamoun AI, Batty GN, Debari VA, et al. Statins may reduce episodes of exacerbation and the requirement for intubation in patients with COPD: evidence from a retrospective cohort study. Int J Clin Pract, 2008, 62(9): 1373-1378.
44. Ingebrigtsen TS, Marott JL, Nordestgaard BG, et al. Statin use and exacerbations in individuals with chronic obstructive pulmonary disease. Thorax, 2015, 70(1): 33-40.
45. Lin CM, Yang TM, Yang YH, et al. Statin Use and the Risk of Subsequent Hospitalized Exacerbations in COPD Patients with Frequent Exacerbations. Int J Chron Obstruct Pulmon Dis, 2020, 15: 289-299.

Chinese Journal of Evidence-Based Medicine

Efficacy and safety of simvastatin in the adjunct therapy of chronic obstructive pulmonary disease: a meta-analysis

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