Department of Clinical Biochemistry (Vascular Disease Prevention Clinics), University College London (UCL) Medical School, London, UK.
Curr Med Res Opin. 2011 Jun;27(6):1191-210. doi: 10.1185/03007995.2011.571239. Epub 2011 Apr 7.
To systematically review and analyse evidence for cholesterol-lowering efficacy of at least 4 weeks of add-on ezetimibe vs doubling statin dose, in adults with primary hypercholesterolaemia.
MEDLINE, EMBASE and Cochrane databases were searched to identify randomised controlled trials of ezetimibe-statin combination vs statin titration (January 1993 - March 2010). Studies were selected using predefined criteria. Two reviewers conducted screening of articles, critical appraisal and data extraction; a third reviewer resolved disagreements. The difference between treatments was analysed for four co-primary outcomes: mean percentage change from baseline in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC); and proportion of patients achieving LDL-C treatment goal. Data were combined by two sets of direct comparison fixed and random effects meta-analysis: (1) compared data in the same treatment period between groups; (2) compared the incremental change in lipid levels of add-on ezetimibe vs doubling statin dose. Heterogeneity was assessed using the I(2) statistic.
Thirteen studies including 5080 patients were included in the meta-analyses. Data on simvastatin, atorvastatin and rosuvastatin were analysed. Results for primary and secondary outcomes were in favour of the ezetimibe-statin combination. A significantly greater percentage reduction in LDL-C levels was achieved in patients treated with ezetimibe-statin vs statin monotherapy (weighted mean difference [WMD]: -14.1% [-16.1, -12.1], p < 0.001). Reduction in LDL-C levels attributed to add-on ezetimibe was significantly greater than that for statin dose doubling (WMD: -15.3% [-19.1, -11.4], p < 0.001). Achievement of LDL-C goal favoured add-on ezetimibe over statin titration and was statistically significant (odds ratio: LDL-C treatment goal 2.45 [1.95, 3.08], p = 0.007).
Meta-analyses were restricted by the limited number of studies with similar trial design and method of statin titration. Results indicate that add-on ezetimibe is significantly more effective in reducing LDL-C levels than doubling statin dose, enabling more patients to achieve LDL-C goal.
系统评价和分析至少 4 周依泽替米贝与他汀类药物加倍剂量联合治疗原发性高胆固醇血症的降胆固醇疗效证据。
检索了 MEDLINE、EMBASE 和 Cochrane 数据库，以确定依泽替米贝-他汀类药物联合治疗与他汀类药物滴定的随机对照试验（1993 年 1 月至 2010 年 3 月）。使用预设标准选择研究。两名审查员进行了文章筛选、批判性评价和数据提取；第三位审查员解决了分歧。通过两组直接比较固定和随机效应荟萃分析分析了四种主要疗效结局的差异：（1）比较两组在同一治疗期内的治疗差异；（2）比较依泽替米贝添加治疗与他汀类药物加倍剂量的血脂水平增量变化。使用 I(2)统计量评估异质性。
纳入了 13 项研究，共 5080 名患者，对辛伐他汀、阿托伐他汀和罗苏伐他汀的数据进行了分析。主要和次要结局的结果均有利于依泽替米贝-他汀类药物联合治疗。依泽替米贝-他汀类药物联合治疗组患者的 LDL-C 水平降低幅度明显大于他汀类药物单药治疗组（加权均数差[WMD]：-14.1%[-16.1，-12.1]，p<0.001）。依泽替米贝添加治疗的 LDL-C 降低幅度明显大于他汀类药物剂量加倍（WMD：-15.3%[-19.1，-11.4]，p<0.001）。依泽替米贝添加治疗组患者达到 LDL-C 目标的比例高于他汀类药物剂量滴定组，且差异具有统计学意义（比值比：LDL-C 治疗目标 2.45[1.95，3.08]，p=0.007）。
荟萃分析受到具有相似试验设计和他汀类药物滴定方法的研究数量有限的限制。结果表明，依泽替米贝在降低 LDL-C 水平方面比他汀类药物剂量加倍更有效，使更多的患者能够达到 LDL-C 目标。
