Ezetimibe alone and in combination lowers the concentration of small, dense low-density lipoproteins in type 2 diabetes mellitus

• Published in: Atherosclerosis Vol. 220; no. 1; pp. 189 - 193
• Main Authors: Winkler, Karl, Jacob, Stephan, Müller-Schewe, Tina, Hoffmann, Michael M., Konrad, Thomas
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.01.2012; Elsevier
• Subjects: absorption; Aged; Analysis of Variance; Anticholesteremic Agents; Anticholesteremic Agents - therapeutic use; Associated diseases and complications; Atherogenic lipoprotein phenotype; atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - blood; Atherosclerosis - etiology; Atherosclerosis - prevention & control; Azetidines; Azetidines - therapeutic use; Biological and medical sciences; Biomarkers; Biomarkers - blood; blood; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; Cardiovascular disease; Centrifugation, Density Gradient; complications; Coronary artery disease; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Down-Regulation; Drug Combinations; drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; etiology; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Female; Germany; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Linear Models; Lipoproteins, LDL; Lipoproteins, LDL - blood; low density lipoprotein cholesterol; Male; Medical sciences; Middle Aged; noninsulin-dependent diabetes mellitus; patients; prevention & control; Risk Assessment; Risk Factors; risk profile; Simvastatin; Simvastatin - therapeutic use; Small, dense LDL; therapeutic use; Time Factors; Treatment Outcome; Type 2 diabetes mellitus; ultracentrifugation; Germany; Cardiovascular disease; Small, dense LDL; Atherogenic lipoprotein phenotype; Type 2 diabetes mellitus; Coronary artery disease; Endocrinopathy; Type 2 diabetes; Small; Ezetimibe; dense LDL; Metabolic diseases; Coronary heart disease; Vascular disease; Lipoprotein LDL; Phenotype; Atherosclerosis; Antilipemic agent
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2011.10.043

The effectiveness of the cholesterol absorption inhibitor ezetimibe on LDL subfractions and ultimately on the atherosclerotic risk profile remains controversial. We thus determined the concentration of atherogenic small, dense LDL (sdLDL) in patients with type 2 diabetes and an elevated cardiovascular risk profile. Multicenter, randomized, open-label 6-week study investigating the effect of ezetimibe 10mg (E), simvastatin 20mg (S) and the combination of ezetimibe-/simvastatin 10/20mg (C) on the concentration of sdLDL separated from fresh plasma by gradient ultracentrifugation in patients with type 2 diabetes (NCT01384058). Fifty-six patients were screened for sdLDL, 41 were randomized, and 40 patients (12 E, 14 S and 14 C) completed the study. Total and LDL cholesterol fell by 14% (p=0.004) and 15% (p=0.006) with E, 22% (p<0.001) and 32% (p<0.001) with S, and 32% (p<0.001) and 44% (p<0.001) with C, respectively. E reduced the concentration of sdLDL by 20% (p=0.043) whereas S and C reduced sdLDL by 24% (p=0.020) and 33% (p=0.003), respectively, and non-sdLDL by 28% (p=0.004) and 42% (p<0.001), respectively. However, the further drop in sdLDL by adding E to S was not significant. Ezetimibe alone and in combination with simvastatin reduced the concentration of atherogenic sdLDL in patients with type 2 diabetes.