Meta-analysis of the cholesterol-lowering effect of ezetimibe added to ongoing statin therapy

D. P. Mikhailidis, G. C. Sibbring, C. M. Ballantyne, G. M. Davies, A. L. Catapano

Research output: Contribution to journalArticlepeer-review


Objective: To review and analyse the evidence for the cholesterol-lowering effect of ezetimibe in adult patients with hypercholesterolaemia who are not at low-density lipoprotein cholesterol (LDL-C) goal on statin monotherapy. Research design: Systematic review and meta-analysis. Methods: MEDLINE and EMBASE were searched to identify ezetimibe randomised controlled trials (RCTs) published between January 1993 and December 2005. The meta-analysis combined data from RCTs, with a minimum treatment duration of 6 weeks, that compared treatment with ezetimibe 10 mg/day or placebo added to current statin therapy. The difference between treatments was analysed for four co-primary outcomes: mean percentage change from baseline in total cholesterol (TC), LDL-C, and high-density lipoprotein cholesterol (HDL-C), and number of patients achieving LDL-C treatment goal. Meta-analysis results are presented for a modified version of the inverse variance random effects model. Results: Five RCTs involving a total of 5039 patients were included in the meta-analysis. The weighted mean difference (WMD) between treatments significantly favoured the ezetimibe/statin combination over placebo/statin for TC (-16.1% (-17.3, -14.8); p <0.0001), LDL-C (-23.6% (-25.6, -21.7); p <0.0001) and HDL-C (1.7% (0.9, 2.5); p <0.0001). The relative risk of reaching the LDL-C treatment goal was significantly higher for patients on ezetimibe/statin relative to those on placebo/statin (3.4 (2.0, 5.6); p <0.0001). In predefined sub-group analyses of studies in patients with coronary heart disease, the WMD between treatments remained significantly in favour of ezetimibe/statin (p <0.0001) for TC and LDL-C but was no longer significant for HDL-C. Elevations in creatine kinase, alanine aminotransferase or aspartate aminotransferase that were considered as an adverse effect did not differ significantly between treatments. Conclusions: The meta-analysis we performed included only five studies and was restricted to analysis of the changes in cholesterol levels relative to baseline. However, the results suggest that ezetimibe co-administered with ongoing statin therapy provides significant additional lipid-lowering in patients not at LDL-C goal on statin therapy alone, allowing more patients to reach their LDL-C goal.

Original languageEnglish
Pages (from-to)2009-2026
Number of pages18
JournalCurrent Medical Research and Opinion
Issue number8
Publication statusPublished - Aug 2007


  • Drug therapy, combination
  • Hypercholesterolaemia
  • Hyperlipidaemia
  • LDL cholesterol
  • Lipoproteins
  • Meta-analysis
  • Review, systematic

ASJC Scopus subject areas

  • Medicine(all)


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