Efficacy And Safety Of Simvastatin In The Adjunct Therapy Of Chronic Obstructive Pulmonary Disease: A Meta-analysis

Objective To systematically review the efficacy and safety of simvastatin in the adjunct therapy of chronic obstructive pulmonary disease（COPD）.Methods Pub Med,EMbase,Web of Science,The Cochrane Library,CNKI,Wan Fang Data,CBM and VIP databases were electronically searched to collect randomized controlled trials（RCTs）on adjunct therapy of simvastatin in patients with chronic obstructive pulmonary disease from inception to December 31^th,2020.We traced the references included in the study in order to supplement and obtain the relevant literature.The retrieval was carried out by the combination of subject words and free words.Two reviewers independently screened literature,extracted data and assessed risk of bias of included studies.If there are differences,they will be resolved through discussion or negotiation with a third party.Then,meta-analysis was performed by using Stata 14.0 software.Result A total of 22 RCTs involving 2377 patients were included.The results of meta-analysis showed that treatment of 20mg simvastatin could improve FEV₁%pred[MD=3.98,95%CI（1.45,6.51）,P=0.002],FEV₁/FVC[MD=3.87,95%CI（2.57,5.18）,P<0.001],and reduce inflammatory indexes such as CRP[MD=-1.97,95%CI（-2.51,-1.43）,P<0.001],hs-CRP[MD=-2.44,95%CI（-4.74,-0.13）,P=0.038],IL-8[SMD=-1.22,95%CI（-2.21,-0.24）,P=0.015]and TNF-a[SMD=-0.76,95%CI（-0.95,-0.57）,P<0.001],while treatment of40mg simvastatin could only optimize the CAT score after adjuvant therapy[MD=-2.10,95%CI（-3.47,-0.73）,P=0.003],and could not improve FEV₁/FVC[MD=5.73,95%CI（-4.89,16.35）,P=0.290],FEV₁%pred[MD=5.36,95%CI（-6.95,17.67）,P=0.394],CRP[MD=-1.39,95%CI（-3.56,0.78）,P=0.209],IL-8[SMD=-1.04,95%CI（-2.30,0.22）,P=0.105],TNF-α[SMD=-0.52,95%CI（-1.97,0.93）,P=0.482].All doses of simvastatin was failed to increase the6-minute walking distance[MD=33.11,95%CI（-15.09,81.32）,P=0.178]or alleviate acute exacerbation[OR=0.47,95%CI（0.14,1.64）,P=0.096].In terms of pulmonary function indexes,meta-analysis was carried out according to the course of treatment.The results showed that the adjuvant treatment time of simvastatin was3 months,FEV₁%pred[MD=-0.28,95%CI（-3.01,2.44）,P>0.05],FEV₁/FVC[MD=1.56,95%CI（-2.31,5.43）,P=0.428]were ineffective,but the treatment time of 6 months was effective for FEV₁%pred[MD=8.05,95%CI（4.93,11.17）,P<0.001],FEV₁/FVC[MD=4.86,95%CI（2.79,6.94）,P<0.001].According to the subgroup analysis of different disease states,the results showed that simvastatin adjuvant therapy was effective on FEV₁%pred in patients with acute exacerbation COPD[MD=13.38,95%CI（2.84,23.93）,P=0.013]and stable COPD[MD=1.48,95%CI（0.54,2.41）,P=0.002].Simvastatin adjuvant therapy was not effective on TNF-a reduction in stable COPD patients[SMD=-0.52,95%CI（-1.04,0.00）,P=0.051],but it was effective on TNF-a reduction in COPD patients in acute exacerbation COPD[SMD=-0.79,95%CI（-1.26,-0.31）,P=0.001].Conclusion Current evidence shows that treatment with 20mg simvastatin may improve pulmonary function,reduce inflammatory index and optimize CAT score in patients with COPD,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.