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Review Article

Comparative efficacy of the addition of ezetimibe to statin vs statin titration in patients with hypercholesterolaemia: systematic review and meta-analysis

, , , , , & show all
Pages 1191-1210 | Accepted 09 Mar 2011, Published online: 07 Apr 2011
 

Abstract

Objective:

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.

Research design and methods:

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 I2 statistic.

Results:

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).

Conclusions:

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.

Transparency

Declaration of funding

This study was funded by Merck & Co., Inc.

Declaration of financial/other relationships

D.P.M. has disclosed that he has been a speaker, advisory board member and research investigator for various pharmaceutical companies (MSD, Genzyme and AstraZeneca), including Merck. He is also CMRO’s Editor-in-Chief. R.W.L., A.L.M. and G.C.S. have disclosed that they are employees of Complete Market Access, a company sponsored by Merck to conduct this study and prepare the manuscript. A.M.T., G.M.D. and K.T. have disclosed that they are employees of Merck & Co, Inc. and own stock and/or stock options in the company.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewer on this manuscript has disclosed that he has no relevant financial relationships.

Acknowledgments

Author contributions include: K.T. and D.P.M. provided specialist input regarding the research question and scope of the analyses, performed critical review of results and assisted in drafting the manuscript. R.W.L. performed all statistical analyses and assisted in drafting the manuscript. A.L.M. and G.C.S. were involved in finalising the scope of the analyses, first- and second-pass screening of articles and data-abstraction stages of the systematic review, and assisted in drafting the manuscript. G.M.D. and A.M.T performed critical review of results and assisted in drafting the manuscript. All authors approved the final version of the manuscript.

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