title: Atorvastatin 10 mg plus ezetimibe 10mg compared with atorvastatin 20 mg: impact on the lipid profile in Japanese patients with abnormal glucose tolerance and coronary artery disease.
abstract: BACKGROUND
  Oxidized low-density lipoprotein (LDL) cholesterol is a sensitive lipid marker for predicting atherosclerosis. Ezetimibe and statins are reported to decrease both LDL cholesterol and oxidized LDL cholesterol. This prospective randomized open-label crossover study compared combination therapy with atorvastatin plus ezetimibe versus high-dose atorvastatin monotherapy. Changes in serum lipids, including malondialdehyde-modified LDL (MDA-LDL) as a representative form of oxidized LDL cholesterol, and glucose metabolism were assessed.
  
  
  RESULTS
  The subjects were 39 Japanese patients with coronary artery disease and type 2 diabetes or impaired glucose tolerance who were taking 10 mg/day of atorvastatin (30 men and 9 women with a mean age of 67.8 years). They were randomized to a group that first received add-on ezetimibe (10 mg/day) or a group that first received atorvastatin monotherapy at a higher dose of 20 mg/day. Both treatments were given for 12 weeks each in a crossover fashion. Add-on ezetimibe significantly decreased MDA-LDL (109.0 ± 31.9 mg/dl to 87.7 ± 29.4 mg/dl, p=0.0009), while up-titration of atorvastatin did not. The decrease with add-on ezetimibe was significantly greater than with up-titration of atorvastatin (p=0.0006). Total cholesterol and LDL cholesterol were significantly decreased by both treatments, but the percent reduction with add-on ezetimibe was significantly greater (p<0.05). High-density lipoprotein cholesterol was significantly increased by both treatments and there was no significant difference between them. The apolipoprotein B/apolipoprotein A-I ratio and remnant-like particle cholesterol were only significantly decreased by add-on ezetimibe. Both treatments caused similar elevation of hemoglobin A(1c).
  
  
  CONCLUSIONS
  In Japanese patients with type 2 diabetes or impaired glucose tolerance and coronary artery disease, adding ezetimibe (10 mg/day) to atorvastatin (10 mg/day) significantly improved the lipid profile compared with atorvastatin monotherapy at 20 mg/day.
authors.affiliation: Department of Cardiology, Cardiovascular Center, Anjo Kosei Hospital, Anjo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Uemura
authors.forename: Masato
authors.initials: M
authors.lastname: Watarai
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishii
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Koyasu
authors.forename: Kenji
authors.initials: K
authors.lastname: Takemoto
authors.forename: Daiji
authors.initials: D
authors.lastname: Yoshikawa
authors.forename: Rei
authors.initials: R
authors.lastname: Shibata
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Matsubara
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D000069059:Atorvastatin; D001384:Azetidines / Q000008:administration & dosage*; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000031:analogs & derivatives / Q000097:blood; D010084:Oxidation-Reduction; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage*
chemical_list: D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D001384:Azetidines; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D008077:Lipoproteins, LDL; D011758:Pyrroles; C569869:malondialdehyde-low density lipoprotein, human; D008315:Malondialdehyde; D002784:Cholesterol; D000069059:Atorvastatin; D000069438:Ezetimibe