Lipid-altering efficacy and safety profile of combination therapy with ezetimibe/statin vs. statin monotherapy in patients with and without diabetes: an analysis of pooled data from 27 clinical trials

Aim: This post hoc analysis compared the lipid‐altering efficacy and safety of ezetimibe 10 mg plus statin (EZE/statin) vs. statin monotherapy in hypercholesterolaemic patients with and without diabetes. Methods: A pooled analysis of 27 previously published, randomized, double‐blind, active‐ or placebo‐controlled clinical trials comprising 21 794 adult patients with (n = 6541) and without (n = 15253) diabetes receiving EZE/statin or statin alone for 4–24 weeks evaluated percentage change from baseline in lipids and other parameters. Consistency of the treatment effect across the subgroups was tested using treatment × subgroup interaction. No multiplicity adjustments were made. Results: Treatment effects within both subgroups were generally consistent with the overall population. EZE/statin was more effective than statin alone in improving low‐density lipoprotein cholesterol (LDL‐C), total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), triglycerides (TGs), non‐HDL‐C, apolipoprotein (apo) B and high‐sensitivity C‐reactive protein (hs‐CRP) in the overall population and both subgroups. Patients with diabetes achieved significantly larger reductions in LDL‐C, TC and non‐HDL‐C compared with non‐diabetic patients. Incidences of adverse events or creatine kinase elevations were similar between groups. A small but significantly higher incidence of alanine aminotransferase or aspartate aminotransferase elevations was seen in patients receiving EZE/statin (0.6%) vs. statin monotherapy (0.3%) in the overall population. Conclusions: Treatment with EZE/statin vs. statin monotherapy provided significantly larger reductions in LDL‐C, TC, TG, non‐HDL‐C, apo B and hs‐CRP and significantly greater increases in HDL‐C, with a similar safety profile in patients with and without diabetes. Reductions in LDL‐C, TC and non‐HDL‐C were larger in patients with diabetes than in patients without diabetes.