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.	中國老年醫學學會呼吸病學分會慢性阻塞性肺疾病學組. 中國老年慢性阻塞性肺疾病臨床診治實踐指南. 中華結核和呼吸雜志, 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.	中華醫學會呼吸病學分會慢性阻塞性肺疾病學組. 慢性阻塞性肺疾病診治指南(2013年修訂版). 中華結核和呼吸雜志, 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.	金曉潔, 王萬鐵, 戴新建, 等. COPD穩定期治療中CAT mMRC與BODE指數的相關性研究及辛伐他汀干預的影響. 數理醫藥學雜志, 2016, (7): 952-955.
13.	余勝忠, 趙宇, 李元廣. 小劑量辛伐他汀對穩定期慢性阻塞性肺疾病患者生活質量的影響. 中國醫學創新, 2014, 11(6): 40-41.
14.	王永彬, 王偉. 辛伐他汀對COPD患者細胞凋亡和炎癥因子的干預作用. 山東大學學報(醫學版), 2009, 47(8): 75-78.
15.	門雪琳, 王永瑞. 辛伐他汀對慢性阻塞性肺病患者緩解期的影響研究. 實用心腦肺血管病雜志, 2011, 19(4): 554-555.
16.	蔣智敏, 歷風元, 童旭芳, 等. 辛伐他汀對慢性阻塞性肺疾病肺功能的影響及作用機制研究. 海南醫學, 2013, 24(9): 1277-1279.
17.	郭新躍. 辛伐他汀對COPD患者肺功能, 血清IL-17, IL-13及脂聯素的影響. 中國現代醫生, 2012, 50(26): 61-63.
18.	陳煥珍, 戢秋明, 李蘭. 辛伐他汀對老年慢性阻塞性肺疾病患者肺功能、免疫功能及生活質量的影響. 臨床肺科雜志, 2016, 21(5): 940-942.
19.	張艷. 辛伐他汀在COPD治療中的臨床應用研究. 中外健康文摘, 2011, 8(47): 250-251.
20.	呂紅, 陶政正, 范桂芹, 等. 辛伐他汀治療慢性阻塞性肺病患者的臨床療效觀察. 現代醫學, 2017, 45(4): 575-578.
21.	吳軼赟, 廖浪霞. 辛伐他汀治療慢性阻塞性肺疾病的療效及其對患者C反應蛋白, 前白蛋白和肺功能的影響. 海南醫學, 2016, 27(23): 3807-3810.
22.	金雪梅, 李曉佳. 辛伐他汀治療慢性阻塞性肺疾病患者療效觀察. 臨床肺科雜志, 2011, 16(7): 1012-1014.
23.	江雪慧. 辛伐他汀對慢性阻塞性肺疾病患者血漿炎癥因子的影響及療效觀察. 中國藥物與臨床, 2012, 12(12): 1602-1603.
24.	金曉博. 辛伐他汀對COPD患者誘導痰炎性標志物、肺功能及臨床癥狀的影響研究. 醫學信息, 2013, 28: 302-303.
25.	陳代剛, 杜飛. 辛伐他汀對慢性阻塞性肺疾病急性加重期患者血清炎性因子, 肺動脈高壓及肺功能的影響. 中國老年學雜志, 2017, 37(14): 3523-3524.
26.	童旭芳, 朱漣敏. 辛伐他汀對慢性阻塞性肺疾病炎癥因子的影響. 江西醫藥, 2015, 50(5): 434-435.
27.	汪國斌. 辛伐他汀治療AECOPD療效. 臨床肺科雜志, 2014, 19(6): 1018-1020.
28.	Kaczmarek P, S?adek 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.	蔡柔熒. 根據臨床案例分析中國ACS患者能否耐受高強度他汀治療. 海峽藥學, 2018, 30(9): 240-243.
37.	周穎, 姜紅, 王勇. 強化他汀治療的種族差異—中國人適合強化他汀治療嗎?. 醫學綜述, 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. 中國老年醫學學會呼吸病學分會慢性阻塞性肺疾病學組. 中國老年慢性阻塞性肺疾病臨床診治實踐指南. 中華結核和呼吸雜志, 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. 中華醫學會呼吸病學分會慢性阻塞性肺疾病學組. 慢性阻塞性肺疾病診治指南(2013年修訂版). 中華結核和呼吸雜志, 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. 金曉潔, 王萬鐵, 戴新建, 等. COPD穩定期治療中CAT mMRC與BODE指數的相關性研究及辛伐他汀干預的影響. 數理醫藥學雜志, 2016, (7): 952-955.
13. 余勝忠, 趙宇, 李元廣. 小劑量辛伐他汀對穩定期慢性阻塞性肺疾病患者生活質量的影響. 中國醫學創新, 2014, 11(6): 40-41.
14. 王永彬, 王偉. 辛伐他汀對COPD患者細胞凋亡和炎癥因子的干預作用. 山東大學學報(醫學版), 2009, 47(8): 75-78.
15. 門雪琳, 王永瑞. 辛伐他汀對慢性阻塞性肺病患者緩解期的影響研究. 實用心腦肺血管病雜志, 2011, 19(4): 554-555.
16. 蔣智敏, 歷風元, 童旭芳, 等. 辛伐他汀對慢性阻塞性肺疾病肺功能的影響及作用機制研究. 海南醫學, 2013, 24(9): 1277-1279.
17. 郭新躍. 辛伐他汀對COPD患者肺功能, 血清IL-17, IL-13及脂聯素的影響. 中國現代醫生, 2012, 50(26): 61-63.
18. 陳煥珍, 戢秋明, 李蘭. 辛伐他汀對老年慢性阻塞性肺疾病患者肺功能、免疫功能及生活質量的影響. 臨床肺科雜志, 2016, 21(5): 940-942.
19. 張艷. 辛伐他汀在COPD治療中的臨床應用研究. 中外健康文摘, 2011, 8(47): 250-251.
20. 呂紅, 陶政正, 范桂芹, 等. 辛伐他汀治療慢性阻塞性肺病患者的臨床療效觀察. 現代醫學, 2017, 45(4): 575-578.
21. 吳軼赟, 廖浪霞. 辛伐他汀治療慢性阻塞性肺疾病的療效及其對患者C反應蛋白, 前白蛋白和肺功能的影響. 海南醫學, 2016, 27(23): 3807-3810.
22. 金雪梅, 李曉佳. 辛伐他汀治療慢性阻塞性肺疾病患者療效觀察. 臨床肺科雜志, 2011, 16(7): 1012-1014.
23. 江雪慧. 辛伐他汀對慢性阻塞性肺疾病患者血漿炎癥因子的影響及療效觀察. 中國藥物與臨床, 2012, 12(12): 1602-1603.
24. 金曉博. 辛伐他汀對COPD患者誘導痰炎性標志物、肺功能及臨床癥狀的影響研究. 醫學信息, 2013, 28: 302-303.
25. 陳代剛, 杜飛. 辛伐他汀對慢性阻塞性肺疾病急性加重期患者血清炎性因子, 肺動脈高壓及肺功能的影響. 中國老年學雜志, 2017, 37(14): 3523-3524.
26. 童旭芳, 朱漣敏. 辛伐他汀對慢性阻塞性肺疾病炎癥因子的影響. 江西醫藥, 2015, 50(5): 434-435.
27. 汪國斌. 辛伐他汀治療AECOPD療效. 臨床肺科雜志, 2014, 19(6): 1018-1020.
28. Kaczmarek P, S?adek 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. 蔡柔熒. 根據臨床案例分析中國ACS患者能否耐受高強度他汀治療. 海峽藥學, 2018, 30(9): 240-243.
37. 周穎, 姜紅, 王勇. 強化他汀治療的種族差異—中國人適合強化他汀治療嗎?. 醫學綜述, 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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