title: Incremental lowering of low-density lipoprotein cholesterol with ezetimibe 20 mg vs 10 mg daily in patients receiving concomitant statin therapy.
abstract: BACKGROUND
  Ezetimibe is typically administered at a dose of 10 mg daily, with few reports of use at other doses. We compared plasma concentrations of low-density lipoprotein (LDL) cholesterol and other lipid variables in patients with dyslipidemia who were receiving ezetimibe 10 mg and then 20 mg daily.
  
  
  METHODS
  A retrospective chart review identified 27 patients who received ezetimibe 10 mg and then 20 mg daily at different times; 15 participants were receiving stable statin therapy and 12 were not receiving concomitant statins. Plasma concentrations of lipids, creatine kinase (CK), and aspartate transaminase (AST) were determined. Plasma concentrations of ezetimibe and ezetimibe glucuronide were measured in a second group of patients.
  
  
  RESULTS
  Patients taking statins and ezetimibe 20 mg had further reductions in total and LDL cholesterol of 7.1% and 10.3%, respectively (both P < 0.05) than did those receiving the 10-mg dose. No difference between 20-mg and 10-mg dosing was seen among patients not receiving statins. Plasma concentrations of ezetimibe and its active metabolite were about 2-fold higher (P < 0.05) in patients taking ezetimibe 20 mg than in those receiving 10 mg daily. All patients tolerated ezetimibe 20 mg without side effects.
  
  
  CONCLUSIONS
  Ezetimibe 20 mg daily reduced total and LDL cholesterol further in patients receiving statin therapy compared with 10 mg daily. Prospective studies are required to show whether the higher plasma levels of ezetimibe and its active metabolite in patients taking the 20-mg dose have any detrimental effects. Increasing the ezetimibe dose to 20 mg daily might be an interesting potential approach for patients who fail to reach lipid targets on ezetimibe 10 mg daily along with maximally tolerated doses of statin.
authors.affiliation: Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ziada
authors.forename: Ute I
authors.initials: UI
authors.lastname: Schwarz
authors.forename: Marianne K
authors.initials: MK
authors.lastname: DeGorter
authors.forename: Rommel G
authors.initials: RG
authors.lastname: Tirona
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Ban
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kim
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001384:Azetidines / Q000008:administration & dosage* / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003402:Creatine Kinase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000188:drug therapy*; D000069438:Ezetimibe; D005260:Female; D020719:Glucuronides / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D020719:Glucuronides; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C511436:ezetimibe glucuronide; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D000069438:Ezetimibe