The efficacy and safety of statin in combination with ezetimibe compared with double-dose statin in patients with high cardiovascular risk: A meta-analysis

Currently, statins are the first-line therapies for dyslipidemia and atherosclerotic cardiovascular disease, however, their hypolipidemic effects have not been satisfactory. We performed a meta-analysis to compare lipid-lowering efficacy and safety of ezetimibe and statin combination therapy with double-dose statin monotherapy in patients with high cardiovascular risk. Fourteen studies involving 3105 participants were included in the final analysis; 1558 (50.18%) participants received ezetimibe and statin combination therapy and 1547 (49.82%) received double-dose statin monotherapy. Eight studies reported the percentages of changes in several lipid parameters from baseline to endpoint in both groups. Lipid parameters changed more significantly in patients coadministered with ezetimibe and statin (low-density lipoprotein cholesterol [LDL-C]: MD = -9.39, 95% CI -13.36 to -5.42; non-high-density lipoprotein cholesterol [non-HDL-C]: MD = -10.36, 95% CI -14.23 to -6.50; total cholesterol [TC]: MD = -8.11, 95% CI -10.95 to -5.26; and triglyceride [TG]: MD = -5.96, 95% CI -9.12 to -2.80), with moderate to high heterogeneity among the studies. Two out of fourteen studies investigated several different statins. Our subgroup analysis showed that, compared with double-dose atorvastatin monotherapy, ezetimibe and atorvastatin combination therapy significantly decreased LDL-C, non-HDL-C, TC, and TG levels by 14.16%, 14.01%, 11.06%, and 5.96%, respectively (p < 0.001). No significant difference was found in the incidence of laboratory-related adverse events (AEs) between statin combination therapy and monotherapy. Overall, ezetimibe and statin combination therapy significantly decreased LDL-C, non-HDL-C, and TC levels in patients with high cardiovascular risk, among which ezetimibe combined with atorvastatin had the best therapeutic effect. Compared with ezetimibe and statin combination therapy, double-dose statin monotherapy did not increase the risk of AEs.