Colesevelam HCl reduces LDL particle number and increases LDL size in hypercholesterolemia.
BACKGROUND
Although LDL-cholesterol (LDL-C) remains the target of cholesterol-lowering therapy, high levels of LDL particle numbers better differentiate cardiovascular risk than LDL-C concentrations. Colesevelam HCl, a novel bile acid sequestrant, has also been shown to reduce mean LDL-C by 18% with the maximum dose. The effect of colesevelam HCl on LDL particle number and particle size has not been previously published. LDL particle number and particle size were measured by NMR spectroscopy.


METHODS
In this multi-center, double-blind, placebo-controlled study, 149 patients with moderate hypercholesterolemia (LDL-C > 160 mg/dL [4.14 mmol/L]; triglycerides < 300 mg/dL [3.39 mmol/L]) were randomized to colesevelam HCl (1.5-3.75 g/d) or placebo for 6 weeks.


RESULTS
Colesevelam HCl reduced LDL particle number by 6.8% at a dosage of 3.0 g/d (P = 0.031), and 13.7% (P = 0.0002) at a dosage of 3.75 g/d. Baseline levels of triglycerides or LDL size did not influence changes in LDL particle number. Further, mean LDL particle size increased with colesevelam HCl 3.75 g/d (1.1% increase versus baseline, P < 0.05).


CONCLUSIONS
For patients with moderate hypercholesterolemia, treatment with colesevelam HCl at the recommended starting dose of 3.75 g/d lowered LDL particle number, and increased mean LDL particle size.
Rosenson
Robert S
RS
Preventive Cardiology Center, Department of Medicine, Division of Cardiology, Northwestern University, The Feinberg School of Medicine, Galter Pavilion, Suite 11-120, 201 East Huron Street, Chicago, IL 60611, USA. r-rosenson@norhwestern.edu
D000499:Allylamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D000069472:Colesevelam Hydrochloride; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D000499:Allylamine; D000069472:Colesevelam Hydrochloride