Comparative safety and efficacy of low- or moderate-intensity statin plus ezetimibe combination therapy and high-intensity statin monotherapy: A meta-analysis of randomized controlled studies

Abstract

Statin is highly recommended for dyslipidemia to prevent atherosclerosis-related cardiovascular diseases and death. The aim of this study was to compare the efficacies and safeties of low/moderate-intensity statin plus ezetimibe combination therapy vs. high-intensity statin monotherapy. Meta-analysis was conducted on data included in published studies performed to compare the effects of the two treatments on lipid parameters and hs-CRP. Safety-related parameters were also evaluated. Eighteen articles were included in the meta-analysis. In terms of efficacy, low/moderate-intensity statin plus ezetimibe reduced LDL-C (SE = 0.307; 95% CI 0.153–0.463), TC (SE = 0.217; 95% CI 0.098–0.337), triglyceride (SE = 0.307; 95% CI 0.153–0.463), and hs-CRP (SE = 0.190; 95% CI 0.018–0.362) significantly more than high-intensity statin therapy. In terms of safety, the two treatments were not significantly different in terms of ALT elevation, but high-intensity statin increased AST and CK significantly more than combination therapy. This analysis indicates that low/moderate-intensity statin plus ezetimibe combined therapy is more effective and safer than high-intensity statin monotherapy, which suggests the addition of ezetimibe to statin should be preferred over increasing statin dose and that high-intensity statin should be used more carefully, especially in patients with related risks.

Intensive lipid lowering agents and coronary atherosclerosis: Insights from intravascular imaging

“…This finding supported results of clinical trials that demonstrated a favorable effect of adding ezetimibe to statin therapy on cardiovascular events in patients with an acute coronary syndrome [44] . While addition of ezetimibe to low or moderate intensity statin therapy may be better tolerated and produce greater lipid lowering than high intensity statin alone [45] , further studies are required to evaluate the impact of these strategies on coronary atheroma.…”

Multifunctional nanoparticle-mediated combining therapy for human diseases

“… 175 – 177 Adding ezetimibe to statin treatment significantly decreases the risk of cardiovascular events and further reduces residual risk in patients already receiving maximally or maximally tolerated statin remedy and in patients with diabetes. 178 – 180 Similarly, involving an inhibitor of protein convertase subtilisin/kexin type 9 (PCSK9) to statin treatment, which can lower plasma LDL levels, demonstrated good therapeutic effects. 181 Compared to statin treatment alone, the combination strategy reduced LDL levels by over 50%.…”

Comparison of Effectiveness of High Dose Statin Monotherapy With Combination of Statin and Ezetimibe to Prevent Cardiovascular Events in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis

“…Regarding safety, there were no significant differences between the two treatments regarding ALT elevation, but high-intensity statin therapy led to a significant increase in AST and CK compared to combination therapy [ 20 ]. Another study highlighted that adherence to moderate-intensity statins plus ezetimibe therapy may be higher compared to high-intensity statin therapy.…”

“…The present meta-analysis does not identify any statistical differences concerning cardiovascular outcomes between the two treatment groups. However, it acknowledges that prior meta-analyses have demonstrated the significant impact of combination therapy on lipid profiles and other biomarkers [ 20 ]. Essentially, while the current study does not observe a statistical advantage, it acknowledges the existing evidence from previous research suggesting benefits in terms of lipid profile and other biomarkers associated with combination therapy.…”