| Background And Objective:Currently,the most commonly used PCSK9 inhibitors in clinical practice are evolocumab and alirocumab.Numerous studies have shown that PCSK9 inhibitors can lower low-density lipoprotein cholesterol(LDL-C)and are used to treat familial hypercholesterolemia.They are also gradually being used to treat coronary heart disease,but their clinical efficacy is still somewhat controversial due to their relatively short application time.Lipoprotein(a)[Lp(a)] also has an impact on coronary heart disease independent of LDL-C,but there is currently no specific drug for lowering Lp(a)in clinical practice.Therefore,we will use the systematic evaluation method of evidence-based medicine to further analyze and compare the clinical efficacy of PCSK9 inhibitors in patients with coronary heart disease and their impact on Lp(a),providing a basis for clinical decision-making.Methods:In order to conduct literature retrieval,we referred to the Cochrane Collaboration and searched computerized electronic databases including Pub Med,the Cochrane Library,Embase,Sinomed(CBM),Web of Science,CNKI,VIP,and Wanfang databases.We conducted the search in each database up to December 31,2022,and limited the search to articles in Chinese and English,and obtained the full-text articles.We screened out randomized controlled trials(RCTs)related to PCSK9 inhibitor therapy for coronary heart disease.Two independent reviewers screened the literature,extracted data,and assessed quality.We used Rev Man 5.4software to assess the risk of bias in the literature,and conducted meta-analyses and generated graphs using Note Express software with clinical overall effective rate and lipoprotein(a)as outcome indicators.Results:A total of 1684 relevant articles were retrieved,and 12 studies were ultimately included,comprising 48,116 patients,with 24,014 in the control group and 24,102 in the treatment group.The average/median follow-up time ranged from 4 weeks to 2.8years.The meta-analysis results showed that compared with placebo or blank control,PCSK9 inhibitors had the following advantages:(1)They could further reduce total cholesterol(MD=-1.11,[95%CI(-1.42,-0.80)],P<0.00001),triglycerides(MD=-0.35,[95%CI(-0.49,-0.21)],P<0.00001),low-density lipoprotein cholesterol(MD=-1.24,[95%CI(-1.28,-1.20)],P<0.00001),and lipoprotein(a)(Lp(a))(MD=-12.55,[95%CI(-17.05,-8.04)],P<0.00001),while increasing high-density lipoprotein cholesterol(HDL-C)(MD=0.08,[95%CI(0.02,0.15)],P=0.01<0.05);(2)They could further reduce hs-CRP(MD=-0.95,[95%CI(-1.33,-0.56)],P<0.00001),IL-6(MD=-1.64,[95%CI(-2.28,-1.00)],P<0.00001),and TNF-α(MD=-1.71,[95%CI(-2.69,-0.73)],P=0.0007<0.05);(3)They could reduce major adverse cardiovascular events(RR=0.86,[95%CI(0.82,0.90)],P<0.00001),reduce the incidence of non-fatal myocardial infarction(P<0.00001),stroke(P=0.0005),and coronary artery revascularization events(P<0.00001),while the differences in all-cause mortality(P=0.14>0.05),heart failure incidence(P=0.73>0.05),and angina pectoris incidence(P=0.17>0.05)were not statistically significant;(4)Except for local reactions at the injection site(P<0.00001),there was no statistically significant difference in the incidence of severe adverse events,events leading to discontinuation,and other common adverse reactions(allergies,muscle pain,new-onset diabetes,elevated liver enzymes,etc.)(P>0.05).Conclusion:In terms of efficacy,PCSK9 inhibitors can improve various lipid parameters,such as reducing TC,TG,LDL-C,Lp(a),while increasing HDL-C,and reducing inflammatory factors and MACE.In terms of safety,except for local injection site reactions,PCSK9 inhibitors do not increase the incidence of other adverse events. |
