Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: A pooled analysis of over 21,000 subjects from 27 clinical trials

Objective: Patients with dyslipoproteinemia constitute the largest risk group for development of atherosclerosis and cardiovascular disease (CVD). Despite extensive statin use, many patients with CVD risk do not achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets. This pooled analysis of 27 previously published clinical trials conducted between 1999 and 2008 evaluated the lipid-altering efficacy and factors related to treatment response of ezetimibe combined with statin and statin monotherapy. Methods: Patient-level data were combined from double-blind, placebo-controlled or active comparator studies randomizing adult subjects to ezetimibe 10 mg plus statin (n = 11,714) versus statin alone (n = 10,517) for 6-24 weeks (mean = 9 weeks). Association of factors with treatment response, percent change from baseline LDL-C and other lipids, and attainment of guideline-recommended lipid and lipoprotein targets were evaluated. Results: Higher baseline LDL-C, diabetes mellitus, Black race, greater age, and male gender were associated with small but significantly greater percent reductions in LDL-C regardless of treatment. Treatment influenced efficacy, with ezetimibe plus statin producing significantly greater reductions in LDL-C, total-cholesterol, non-HDL-C, ApoB, triglycerides, lipid ratios, hs-CRP; significantly larger increases in HDL-C and ApoA1; and significantly higher achievement of LDL-C (<70 mg/dl, <100 mg/dl), non-HDL-C (<100 mg/dl, <130 mg/dl), and ApoB (<80 mg/dl, <90 mg/dl) targets than statin monotherapy at statin potencies compared (p < 0.0001 for all). Differential treatment effects were seen with first-/second-line therapy and statin potency. Conclusion: These results suggest that patient characteristics have a limited influence on response to lipid-lowering therapy and demonstrate the consistent treatment effect of ezetimibe combined with statin and statin monotherapy across a diverse patient population. (C) 2012 Elsevier Ireland Ltd. All rights reserved.