Lipid-Lowering Efficacy of Ezetimibe in Patients with Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analyses

Abstract

Introduction: Patients with atherosclerotic cardiovascular disease (ASCVD), especially those with recent (< 1 year) acute coronary syndrome (ACS), are at high risk for recurrent cardiovascular events. This risk can be reduced by lowering low-density lipoprotein cholesterol (LDL-C) levels. A comprehensive meta-analysis on the LDL-C-lowering efficacy of ezetimibe is lacking. This study attempts to address this gap.

Methods: A systematic literature review of randomized controlled trials evaluating the LDL-C-lowering efficacy of ezetimibe in the ASCVD population was conducted. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for publications from database inception to August 2018 and for conference abstracts from 2015 to August 2018. Meta-analyses were conducted to evaluate the LDL-C-lowering efficacy of ezetimibe in the ASCVD population and the recent ACS subgroup.

Results: In total, 12 studies were eligible for the meta-analyses. Treatment with combination ezetimibe plus statin therapy showed greater absolute LDL-C reduction than statin monotherapy (mean difference - 21.86 mg/dL; 95% confidence interval [CI] - 26.56 to - 17.17; p < 0.0001) after 6 months of treatment (or at a timepoint closest to 6 months). Similarly, in patients with recent ACS, combination ezetimibe plus statin therapy was favorable compared with statin monotherapy (mean treatment difference - 19.19 mg/dL; 95% CI - 25.22 to - 13.16; p < 0.0001).

Conclusions: Ezetimibe, when added to statin therapy, provided a modest additional reduction in LDL-C compared with statin monotherapy. However, this may not be sufficient for some patients with ASCVD who have especially high LDL-C levels despite optimal statin therapy.

Fig. 1

Study flow diagram of the systematic review. Overall, 14 records were identified through the systematic literature review that reported on patients with ASCVD, that assessed ezetimibe therapy (received with or without other lipid-lowering therapies), and reported LDL-C change, LDL-C at endpoint, or both. Of these, 12 records contained adequate and independent information sufficient for meta-analysis, including nine reporting on two-arm trials and three reporting on multi-arm trials. ^a115 records were manually entered, and four additional records were cited in protocols. ASCVD atherosclerotic cardiovascular disease, LDL-C low-density lipoprotein cholesterol

Fig. 2

Treatment difference in mean LDL-C change (mg/dL) from baseline between combination ezetimibe plus statin therapy and statin monotherapy comparator at 6 months or at the reported timepoint closest to 6 months. ^aMeta-analysis included 19,404 participants from 12 studies, who received treatment (ezetimibe + statin vs. statin) for a mean duration of 11.56 months. *p < 0.0001. CI confidence interval, LDL-C low-density lipoprotein cholesterol, MD mean difference, RE random effects

Fig. 3

Subgroup analysis: LDL-C change (mg/dL) from baseline at 6 months, or at the reported timepoint closest to 6 months, limited to studies including patients with recent acute (< 1 year) coronary syndrome (Meta-analysis included 18,436 participants from four studies, who received treatment [ezetimibe plus statin vs. statin] for a mean duration of 11.90 months). *p < 0.0001. CI confidence interval, LDL-C low-density lipoprotein cholesterol, MD mean difference, RE random effects