Abstract 668: Lipoprotein Particle Size Effects of Colesevelam HCl in Combination with Ezetimibe and Simvastatin
Lipid-lowering combination therapy is often required to achieve low density lipoprotein cholesterol (LDL-C) goals and to favorably affect other lipid parameters. This is the first double-blind, parallel-group study to evaluate colesevelam (COL), ezetimibe (EZE) and simvastatin (SIM) vs. EZE and SIM alone in subjects with primary hypercholesterolemia (LDL-C ≥130 mg/dL and triglycerides <400 mg/dL). Subjects (N=85) were randomized 1:1 to COL 3.75 g/d + EZE 10 mg/d or placebo + EZE 10 mg/d for 6 weeks, followed by SIM 20 mg/d to both groups for 4 additional weeks. At week 10, both COL + EZE + SIM and EZE + SIM regimens substantially reduced LDL-C (−57% and −51%, respectively). More subjects achieved an LDL-C goal <70mg/dL with COL + EZE + SIM than with EZE + SIM (52.4% 22/42 vs 23.3% 10/43, p<0.01). Both regimens decreased hsCRP, Apo B, LDL subfraction particle concentrations, all lipoprotein ratios, and increased Apo AI, as well as increased HDL and VLDL particle size compared to baseline. COL+EZE+SIM did not change LDL particle size (which actually decreased in the EZE + SIM group to a mild, but significant degree). The use of COL + EZE + SIM did not result in any safety or unexpected tolerability issues. Compliance with study medication was >95% for both groups; >90% of subjects in each group completed the study. COL + EZE + SIM combination therapy was associated with greater attainment of aggressive LDL-C goals, greater improvement in lipoprotein ratios, reduction in LDL particle concentration, and greater increase in Apo AI, and is a useful therapeutic regimen for high-risk patients with primary hypercholesterolemia who are not achieving LDL-C treatment goals.