Comparing The Efficacy And Safety Of Ezetimibe And Statin Combination Therapy Versus Statin Intensive Monotherapy In Patients With Coronary Heart Disease

Background:Statins are the cornerstone of the treatment of coronary heart disease.Ezetimibe is the most commonly used non-statin drug.Statins and ezetimibe can be used in combination to reduce lipids in different ways.However,the efficacy of statins and ezetimibe combination therapy or statin monotherapy is still controversial.Objective: We aim to evaluate the efficacy and safety of ezetimibe and statin combination therapy vs.statins intensive monotherapy in patients with coronary heart disease.Method:(1)Retrospective analysis: The clinical data of patients diagnosed with coronary heart disease in our hospital from January 2016 to June 2019 were collected,and the basic conditions of the selected 146 patients were similar by means of propensity score matching.According to their lipid-lowing regimen was divided into two groups: group A was a statin intensive monotherapy group: High-dose statin treatment group(n=73);group B was a combination therapy: ezetimibe combined with medium-dose statin treatment group(n=73).The patients were followed-up for 3 months to compare the blood lipid levels and adverse reactions before and after treatment.(2)Meta-analysis: We preformed electronic searches using tools such as Pubmed,Embase and the Cochrane Library,and all literature were randomized controlled studies on ezetimibe combined with statin and statin intensive monotherapy in treatment of patients at high/very high risk of coronary heart disease.The claim period is from January 1997 to March 2019,and follow-up time was≥6 weeks.Metaanalysis was performed using Revman5.1 and Stata 12.0 software.Result:(1)Retrospective analysis: After three months of follow-up,in terms of effectiveness,in the combination therapy group,lipid change from baseline was reduce more significant,LDL-C(-1.27±0.75 vs.-1.05±0.47,P=0.044),TC(-1.56±0.94 vs.-1.21±0.62,P=0.011),non-HDL-C(-1.58±0.86 vs.-1.25±0.65,P=0.046),TG(-0.56±0.47 vs,-0.40±0.42,P=0.039).The combination therapy group was significantly increased HDL-C more than that in statin monotherapy group(0.10±0.19 vs.0.04±0.19,P=0.046).In terms of safety,there were no significant differences in ALT≥3×ULN,rhabdomyolysis or CK≥10×ULN between the two groups(P>0.05).(2)Meta-analysis: Fifteens studies involving 5391 patients were included in this review.The results showed: compared with statin intensive monotherapy,the overall efficacy of ezetimibe and statin combination therapy was better at lowering blood lipid levels as determined from the LDL-C(SMD=-0.67,95%CI=-0.81～-0.54,P<0.01),TC(SMD=-0.63,95%CI=-0.78～-0.48,P<0.01),TG(SMD=-0.23,95%CI=-0.29～-0.17,P<0.01),non-HDLC(SMD=-10.73,95%CI=-16.32～-5.14 P<0.01).Moreover,combination therapy significantly elevated HDL-C levels(SMD=0.08,95%CI=0.02～0.13,P<0.01).There were no significant differences for the decreasing levels of hs-CRP(SMD=-0.10,95%CI=0.02～0.13,P=0.13).And the compliance rate of the combination therapy was higher than that of the statin monotherapy(RR=1.73.95%CI=1.43～2.08,P<0.01).There was no significant difference in the incidence of adverse effects between the combination treatment group and statin monotherapy group,with ALT≥3×ULN(RR:0.62,95%CI=0.23～1.64,P=0.33)and CK≥10×ULN(RR:0.33,95%CI=0.05～2.12,P=0.25).Conclusion: Compared with statin monotherapy,ezetimibe and statin combination therapy can significantly reduce LDL-C,TC,TG,and non-HDL-C,and LDL-C compliance rate was higher,and combination therapy can elevate HDL-C levels better than statin intensive monotherapy.In terms of adverse reactions,there was no significant difference between the two groups.