| Aims:To explore efficacy and safety of moderate-intensity statin plus ezetimibe therapy compared with high-intensity statin monotherapy.Background:Cardiovascular disease remains the leading cause of death worldwide.The burden of the disease is particularly high.Dyslipidemia,especially low density lipoprotein cholesterol(LDL-C),is an important risk factor for atherosclerotic cardiovascular disease(ASCVD).More intensive LDL-C lowering based on intensity-statin therapy reduces clinical outcomes in people with cardiovascular risk.However,adverse effects are more common with intensity-statin therapy.The combination of ezetimibe with the lower statin dose seems to be more effective and safer.It represents possible approaches for people intolerant to statins.Due to the lack of convincing clinical evidence,we performed a meta-analysis of recent randomized controlled trials(RCTs).Methods:We conducted comprehensive searches of PubMed,Embase and Cochrane from March 2004 to March 2019.We included any RCT evaluating either atorvastatin 20 mg/d plus ezetimibe 10 mg/d with atorvastatin 40 mg/d or rosuvastatin 10 mg/d plus ezetimibe 10 mg/d with rosuvastatin 20 mg/d.Two reviewers independently extracted data.Our main endpoints were mean difference(MD)of change in blood lipids and risk ratio(RR)of adverse events.We used Stata(version 13.0)for all statistical analyses.A fixed-effects model(Inverse variance method or Mantel-Haenszel mehod)was used in this meta analysis.We used the Cochran Q test and I2 testing to assess heterogeneity between studies.We also carried out a subgroup analysis based on atorvastatin and rosuvastatin.Results:We identified 10 RCTs enrolling a total of 1366 participants.We did find statistically significant effects on LDL-C(MD-11.16%,95%CI:-13.47%?-8.85%,I2=80%,P<0.001),Apo-B(MD-11.2%,95%CI:-13.58%-8.81%,I2=58.2%,P=0.035),non-HDL-C(MD-12.97%,95%CI:-15.65%?-10.30%,12=60.7%,P=0.026)and TC(MD-9.52%,95%Cl:-11.63%?-7.41%,I2=75.8%,P=0.002).However,there were no statistically significant effects on TG(MD-4.12%,95%CI:-8.45%?0.21%,I2-=22.6%,P=0.257)and HDL-C(MD 0.94%,95%CI:-1.37%?3.25%,12=0,P=0.853).Because of significant between-study heterogeneity,we did subgroup analysis and found no heterogeneity.The subgroup's efficacy of atorvastatin subgroup was significantly better than rosuvastatin subgroup with LDL-C(MD-19.61%vs-4.88%,P<0.001),Apo-B(MD-13.23%vs-5.39%,P=0.005)and non-HDL-C(MD-15.61%vs-6.33%,P=0.002).The atorvastatin subgroup also showed difference on TC(MD-12.11%)and TG(MD-6.07%).We also found statistically significant effects on adverse events(RR 0.36,95%CI:0.17?0.76,I2=0,P=0.875).Gastrointestinal disorders were the most common events.However,there were no statistically significant effects on gastrointestinal disorders(RR 0.73,95%Cl:0.30?1.82,I2=3.5%,P=0.387).Conclusion:Available evidence suggests that moderate-intensity statin plus ezetimibe therapy is better than high-intensity statin monotherapy on blood lipids and safety. |
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