title: Comparison of effects of morning versus evening administration of ezetimibe/simvastatin on serum cholesterol in patients with primary hypercholesterolemia.
abstract: BACKGROUND
  Ezetimibe, a first-in-its-class inhibitor of cholesterol absorption, is an effective agent for combined use with statins to achieve low-density lipoprotein cholesterol (LDL-C) goals. Ezetimibe in combination with simvastatin as a single-tablet formulation has proven to be highly effective in reducing serum LDL-C through the dual inhibition of cholesterol absorption and biosynthesis. The effect of time of administration on efficacy of this combination therapy has not been evaluated.
  
  
  OBJECTIVE
  To compare the effects of morning versus evening administration of ezetimibe/simvastatin on serum cholesterol levels of patients with primary hypercholesterolemia.
  
  
  METHODS
  In this multicenter, open-label, randomized, 2-sequence, 2-period crossover study, patients with primary hypercholesterolemia randomly received ezetimibe/simvastatin 10 mg/20 mg once daily, either in the morning (within 1 hour of breakfast) or in the evening (within 1 hour of dinner) for 6 weeks.
  
  
  RESULTS
  Data on 171 patients (87 in the morning administration group and 84 in the evening administration group) were analyzed. A significant reduction (p ≤ 0.001) in the total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL-C, apo-lipoprotein B, and high-sensitivity C-reactive protein (hs-CRP) from baseline was achieved after each treatment. Noninferiority of morning administration versus evening administration was shown in the percentage reduction of the LDL-C level from baseline (difference, -1.62%; 90% CI -4.94 to 1.70). No significant difference was found between groups with respect to the percentage of changes in other lipid parameters from baseline. Furthermore, there was no significant difference in the percentage of change in hs-CRP as an antiinflammatory marker between the morning and evening administration groups. The frequency of adverse events was similar between groups.
  
  
  CONCLUSIONS
  Morning administration of ezetimibe/simvastatin 10 mg/20 mg is noninferior to evening administration with respect to LDL-C-lowering ability.
authors.affiliation: Department of Internal Medicine, Sun General Hospital, Cardiovascular Center, Daejeon, Korea.
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Yoon
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Jeong Kyung
authors.initials: JK
authors.lastname: Kim
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Ko
authors.forename: Jae Ee
authors.initials: JE
authors.lastname: Ko
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Moon Gi
authors.initials: MG
authors.lastname: Park
authors.forename: Jae Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Hyon
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001384:Azetidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood*; D018592:Cross-Over Studies; D055870:Drug Chronotherapy; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D057194:Intention to Treat Analysis; D008055:Lipids / Q000097:blood; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D010352:Patient Dropouts; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D008055:Lipids; D002097:C-Reactive Protein; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases