Efficacy of Statin/Ezetimibe for Secondary Preventionof Atherosclerotic Cardiovascular Disease in Asian Populations: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Abstract

Several clinical trials have investigated the effect of statin/ezetimibe combination therapy on secondary prevention of atherosclerotic cardiovascular disease (ASCVD)in the Asian population. This study aimed to summarize study results regarding the effect of statin/ezetimibe combination therapy on lipid parameters and highly sensitive C-reactive protein (HsCRP) biomarkers in ASCVD patients from Asian countries. We searched the PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar databases for relevant papers published from 2008 to June 2020. We included randomized controlled trials (RCTs) that (1) were conducted in ASCVD patients in Asian countries; (2) examined the effects of statin/ezetimibe combination therapies compared with a control group; and (3) reported sufficient data on lipid parameters and HsCRP biomarkers. The results were reported as weighted mean differences (WMDs) with 95% confidence intervals (CI) using random-effects models. Funnel plots and Egger's regression test were used to assess publication bias. Twenty-four RCTs were reviewed and 20 were included in the meta-analysis. A total of 4344 participants were included (n = 2197 in the intervention group and n = 2147 in the control group), and the intervention durations ranged from 6weeks to 3.6years. Ezetimibe coadministered with statin therapy, compared with control treatment, significantly reduced low-density lipoprotein cholesterol (LDL-C; n = 20 studies) [WMD - 0.39mmol/L, 95% CI - 0.73 to - 0.05; p < 0.001], triglycerides (TG; n = 18 studies) [WMD - 0.23mmol/L, 95% CI - 0.33 to - 0.13; p < 0.001], and total cholesterol (TC; n = 17 studies) [WMD - 0.31mmol/L, 95% CI - 0.45 to - 0.17; p < 0.001). Although the effect of statin/ezetimibe combinations on high-density lipoprotein cholesterol (HDL-C; n = 17 studies) [WMD 0.02mmol/L, 95% CI - 0.05 to 0.09; p < 0.001) was very minimal and no effect was observed on HsCRP levels (n = 11 studies). Our study found that statin/ezetimibe combinations reduced LDL-C, TC, and TG levels but had minimal effects on HDL-C and no effect HsCRP biomarkers in ASCVD patients. The statin/ezetimibe therapy enabled a more effective reduction in LDL-C levels; however, the duration of the treatment was suboptimal.