title: Lipid-lowering effects of colesevelam HCl in combination with ezetimibe.
abstract: OBJECTIVE
  The primary aim of this study was to compare the effect of colesevelam HCl in combination with ezetimibe to ezetimibe monotherapy on low-density lipoprotein cholesterol (LDL-C) levels in subjects with primary hypercholesterolemia.
  
  
  METHODS
  Subjects with primary hypercholesterolemia (N = 86) were enrolled in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. After a 4- to 8-week washout period, subjects received colesevelam HCl 3.8 g/day plus ezetimibe 10 mg/day or colesevelam HCl placebo plus ezetimibe 10 mg/day for 6 weeks. The primary efficacy endpoint was the mean percent change in LDL-C during randomized treatment. Secondary endpoints included mean absolute change in LDL-C, mean absolute and mean percent change in levels of high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), apolipoprotein (apo) A-I and apo B, and median absolute and percent changes in triglycerides (TG) and high-sensitivity C-reactive protein from baseline to end of treatment. Of the 86 subjects randomized to treatment, 85 were included in the intent-to-treat analysis.
  
  
  RESULTS
  After 6 weeks of treatment, colesevelam HCl plus ezetimibe produced a mean percent change in LDL-C of -32.3% versus -21.4% with ezetimibe monotherapy (p < 0.0001). Colesevelam HCl plus ezetimibe was significantly more effective than ezetimibe alone at producing mean percent reductions in TC, non-HDL-C, and apo B and increases in apo A-I (p < 0.005 for all). Neither treatment regimen resulted in significant changes in median TG levels compared with baseline (p = NS). Both treatments were safe and generally well tolerated.
  
  
  CONCLUSIONS
  Colesevelam HCl plus ezetimibe combination therapy significantly reduced mean LDL-C, TC, non-HDL-C, and apo B levels and increased apo A-I levels (p < 0.005 for all) without significantly increasing median TG levels in hypercholesterolemic subjects compared with ezetimibe alone. Although limited in that atherosclerotic coronary heart disease outcomes were not evaluated, this study demonstrated that combining colesevelam HCl with ezetimibe is a therapeutic option in hypercholesterolemic patients, such as those in whom statins are contraindicated and/or who may have intolerances to statin therapy.
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center Inc., Louisville, KY 40213, USA. hbaysmd@aol.com
authors.forename: Harold
authors.initials: H
authors.lastname: Bays
authors.forename: James
authors.initials: J
authors.lastname: Rhyne
authors.forename: Stacey
authors.initials: S
authors.lastname: Abby
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Lai
authors.forename: Michael
authors.initials: M
authors.lastname: Jones
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000499:Allylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D000069472:Colesevelam Hydrochloride; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D016896:Treatment Outcome
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D001384:Azetidines; D000960:Hypolipidemic Agents; D000499:Allylamine; D002784:Cholesterol; D000069438:Ezetimibe; D000069472:Colesevelam Hydrochloride