Impact of ezetimibe on plasma lipoprotein(a) concentrations as monotherapy or in combination with statins: a systematic review and meta-analysis of randomized controlled trials

The aim of this meta-analysis of randomized placebo-controlled clinical trials was to assess the effect of ezetimibe on plasma lipoprotein(a) concentrations. Only randomized placebo-controlled trials investigating the impact of ezetimibe treatment on cholesterol lowering that include lipoprotein(a) measurement were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases (from inception to February 26^th, 2018). A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate the impact of potential confounders on lipoprotein concentrations. This meta-analysis of data from 10 randomized placebo-controlled clinical trials (15 treatment arms) involving a total of 5188 (3020 ezetimibe and 2168 control) subjects showed that ezetimibe therapy had no effect on altering plasma Lp(a) concentrations (WMD: −2.59%, 95% CI: −8.26, 3.08, p = 0.370; I² = 88.71%, p_(Q) < 0.001). In the subgroup analysis, no significant alteration in plasma Lp(a) levels was observed either in trials assessing the impact of monotherapy with ezetimibe versus placebo (WMD: −4.64%, 95% CI: −11.53, 2.25, p = 0.187; I² = 65.38%, p_(Q) = 0.005) or in trials evaluating the impact of adding ezetimibe to a statin versus statin therapy alone (WMD: −1.04%, 95% CI: −6.34, 4.26, p = 0.700; I² = 58.51%, p_(Q) = 0.025). The results of this meta-analysis suggest that ezetimibe treatment either alone or in combination with a statin does not affect plasma lipoprotein(a) levels.