Ezetimibe and Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analyses

Introduction Individuals diagnosed with atherosclerotic cardiovascular disease (ASCVD), particularly those who have experienced acute coronary syndrome (ACS) within the past year, are at a heightened risk of recurrent cardiovascular events. Lowering low-density lipoprotein cholesterol (LDL-C) levels has been proven effective in reducing this risk. However, there is a lack of a comprehensive meta-analysis investigating the LDL-C-lowering effectiveness and coronary atherosclerotic plaque compositions of Ezetimibe. This study aims to address this gap in knowledge. Methods We conducted a systematic review of randomized controlled trials that evaluated the LDL-C-lowering efficacy and coronary atherosclerotic plaques efficacy of ezetimibe in patients with ASCVD. We searched relevant databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, for publications from database inception until Jul 2023. Meta-analyses were performed to assess the LDL-C-lowering and coronary atherosclerotic plaques efficacy of ezetimibe in the overall ASCVD population. Results The meta-analysis included a total of 20 eligible studies. Our findings revealed that combination therapy of ezetimibe with statins resulted in a more substantial absolute reduction in LDL-C compared to statin monotherapy (mean difference of (−14.06 mg/dL; 95% confidence interval [CI] −18.0 to −10.0; p = 0.0001) after 6-12 months of treatment (or at a time point nearest to 6 -12months). Moreover, the subgroups analysis indicates that the intervention measures were effective in reducing the volume of fibro-fatty plaque (FFP) when compared to the control group [weighted mean difference (WMD) = -1.01, 95% confidence interval (CI) (-3.6 and 1.6), and p = 0.003], necrotic core (NC) volume [WMD =-5.41, 95% CI(-13.3 and 2.5), and p = 0.35], and change dense calcification (change DC) volume [WMD =-1.14, 95% CI (- 1.4 and – 0.8), and p = 0.62] between the treatment group and the control group. Conclusions Our study indicates that the addition of ezetimibe to statin therapy results in a modest yet significant further reduction in LDL-C compared to statin monotherapy. Ezetimibe led to a significant reduction in FFP volume; however, there were no statistically significant differences observed for NC, or change DC volumes.