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

• Published in: Atherosclerosis Vol. 223; no. 2; pp. 251 - 261
• Main Authors: Morrone, Doralisa, Weintraub, William S., Toth, Peter P., Hanson, Mary E., Lowe, Robert S., Lin, Jianxin, Shah, Arvind K., Tershakovec, Andrew M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.08.2012; Elsevier
• Subjects: adults; adverse effects; Aged; Anticholesteremic Agents; Anticholesteremic Agents - adverse effects; Anticholesteremic Agents - therapeutic use; atherosclerosis; Atherosclerosis (general aspects, experimental research); Azetidines; Azetidines - adverse effects; Azetidines - therapeutic use; Biological and medical sciences; Biomarkers; Biomarkers - blood; blood; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; cholesterol; Cholesterol, LDL; Cholesterol, LDL - blood; clinical trials; Clinical Trials as Topic; diabetes mellitus; drug therapy; Drug Therapy, Combination; Evidence-Based Medicine; Ezetimibe; Female; gender; General and cellular metabolism. Vitamins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypercholesterolemia; Hypercholesterolemia - blood; Hypercholesterolemia - drug therapy; low density lipoprotein; Male; Medical sciences; Middle Aged; patients; Pharmacology. Drug treatments; risk; Statin; therapeutic use; therapeutics; Treatment Outcome; triacylglycerols; Hypercholesterolemia; Ezetimibe; Statin; Human; Metabolic diseases; Lipids; Cardiovascular disease; Hyperlipoproteinemia; Statin derivative; Lipoprotein; Cholesterol; Vascular disease; Treatment; Atherosclerosis; Dyslipemia; Antilipemic agent
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2012.02.016

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. Patient-level data were combined from double-blind, placebo-controlled or active comparator studies randomizing adult subjects to ezetimibe 10mg 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. 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 (<70mg/dl, <100mg/dl), non-HDL-C (<100mg/dl, <130mg/dl), and ApoB (<80mg/dl, <90mg/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. 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.