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

ABSTRACT

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 pre-defined 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.