BACKGROUND The aim of this study was to compare and summarize the lipid-altering effects of combination therapy with ezetimibe and statins (E/S) and a double dose of statin (D/S) monotherapy on patients with hypercholesterolemia. 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.

中文翻译：

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依泽替米贝和他汀类药物联合治疗与双重剂量他汀类药物单一治疗对高胆固醇血症参与者的疗效：一项文献荟萃分析。

背景技术本研究的目的是比较和总结依泽替米贝和他汀类药物（E / S）联合治疗和双重剂量他汀类药物（D / S）单一疗法对高胆固醇血症患者的脂质改变作用。方法我们对2个医学数据库PubMed和EMBASE进行了搜索，以确定所有相关研究。进行荟萃分析以阐明两组的疗效。只有双盲随机对照研究（RCT）评估依泽替米贝和他汀类药物以及双重剂量他汀类药物在高胆固醇血症参与者中的两组疗效，该研究检查了低密度脂蛋白胆固醇（LDL-C），总胆固醇（TC）和包括高密度脂蛋白（HDL）。两名评论者独立地从所有基础研究中提取了数据。主要数据是LDL-C的水平，终点处的TC和HDL-C浓度以平均值和标准偏差（SD）表示。结果总共进行了11项双盲，主动或安慰剂对照研究，其中将1926名高胆固醇血症的成年人随机分配到依泽替米贝10 mg进行中的他汀类药物（N = 994）或他汀滴定（加倍）（N = 932）中，作为整体meta -分析。使用随机或固定效应模型，通过加权平均差（MD）评估单个研究中治疗组之间的效应大小。结果显示，E / S组参与者的LDL-C明显降低[MD = -13.14 mg / dL，95％CI（-16.83，-9.44），p = 0.00001]和TC浓度[MD = -23.79 mg / dL，与D / S组相比，从基线到随访的95％CI（-38.65，-8.93），p = 0.002]。除了，对于HDL-C的浓度，没有观察到显着的组间差异[MD = 0.46 mg / dL，95％CI（-1.14，2.06），p = 0.57]。根据亚组分析，依泽替米贝和阿托伐他汀（10毫克）[MD = -16.98 mg / dL，p <0 .0001]或辛伐他汀（20 mg）[MD = -17.35 mg / dL，p <0 .0001 ]显示出比ezetimibe和rosuvastatin（10 mg）组合更强的降低LDL-C的能力[MD = -9.29 mg / dL，p = 0.05]。两组之间的LDL-C短期（终点时间在6至16周之间）和长期（52周）治疗的疗效均未显示明显差异。此外，只有来自亚洲的接受联合疗法治疗的参与者的LDL-C浓度显着降低[MD = -14.7 mg / dL，p <0 .0001]。结论在他汀类药物中添加依折麦布似乎比降低他汀类药物剂量两倍更有效降低LDL-C和TC浓度。此外，根据这项荟萃分析，降低依折麦布和不同他汀类药物联合治疗或降低地理位置参与者的胆固醇水平的能力可能会有所不同，但需要更多样本进行验证。