METHODS: We conducted search on 2 medical databases, PubMed and EMBASE to identify all relevant studies. A meta-analysis was performed to clarify the efficacy in the two groups. Only double-blind Randomized controlled study (RCTs) of efficacy evaluation in the two groups with
ezetimibe and
statins and a double dose of
statin in participants with
hypercholesterolemia that examined
low-density lipoprotein cholesterol (
LDL-C), total
cholesterol (TC) and
high-density lipoprotein (HDL) were included. Two reviewers extracted data from all primary studies independently. The primary data were the level of
LDL-C, TC and HDL-C concentrations at the end point and are expressed as mean and standard deviation (SD).
RESULTS: A total of 11 double-blind, active or placebo-controlled studies with 1926
hypercholesterolemia adults randomized to
ezetimibe 10 mg added to ongoing
statins (N = 994) or
statin titration (doubling) (N = 932) were pooled for the global meta-analysis. The effect size between treatment groups within individual studies was assessed by weighted mean difference (MD) using a random- or fixed-effect model. The result showed that the participants in E/S group get obvious lower
LDL-C [MD = -13.14 mg/dL, 95%CI (-16.83, -9.44), p = 0.00001] and TC concentration [MD = -23.79 mg/dL, 95%CI (-38.65, -8.93), p = 0.002] from baseline to follow-up, comparing to the D/S group. Besides, no significant between-group differences were observed for concentrations of HDL-C [MD = 0.46 mg/dL, 95%CI (- 1.14, 2.06), p = 0.57]. According to subgroup analysis, the combination of
ezetimibe and
atorvastatin (10 mg) [MD = -16.98 mg/dL, p < 0 .0001] or
simvastatin (20 mg) [MD = -17.35 mg/dL, p < 0 .0001] showed stronger ability of reducing
LDL-C than combination of
ezetimibe and
rosuvastatin (10 mg) [MD = -9.29 mg/dL, p = 0.05]. The efficacy of short-term (endpoint time between 6 to 16 week) and long-term (52 week) treatment in the
LDL-C between two groups did not show significant differences. Besides, only participants from Asia treated with combination
therapy were associated with a significant lower
LDL-C concentration [MD = -14.7 mg/dL, p < 0 .0001].
CONCLUSIONS: The addition of
ezetimibe to
statin appears to be more effective on reducing
LDL-C and TC concentrations than doubling the
statin dose. Moreover, the ability to reduce
cholesterol levels of combinations
therapy with
ezetimibe and different
statins or to participants from different geographic location may vary, based on this meta-analysis, while more samples are needed to verify.