title: Effect of simvastatin/ezetimibe 10/10 mg versus simvastatin 40 mg on serum vitamin D levels.
abstract: BACKGROUND
  Low levels of 25-hydroxyvitamin D (25(OH)VitD) have been recognized as an emerging cardiovascular disease (CVD) risk factor. Statins are reported to increase 25(OH)VitD concentration. Animal studies suggest that ezetimibe is a moderate inhibitor of intestinal 25(OH)VitD absorption, but its effect in humans is unknown.
  
  
  OBJECTIVE
  To investigate whether combined treatment with simvastatin/ezetimibe 10/10 mg would increase 25(OH)VitD levels compared to simvastatin 40 mg monotherapy in patients with primary hypercholesterolemia.
  
  
  METHODS
  In a Prospective Randomized Open-label Blinded End point study, 50 patients with primary hypercholesterolemia received either simvastatin/ezetimibe 10/10 mg (n = 25) or simvastatin 40 mg (n = 25) daily for 3 months. The primary end point was between-group difference in the change of serum 25(OH)VitD levels.
  
  
  RESULTS
  Simvastatin/ezetimibe 10/10 mg was associated with a 36.7% increase in 25(OH)VitD serum levels (from 6.8 to 9.3 ng/mL, P = .000), while simvastatin 40 mg was associated with a 79.1% increase (from 6.7 to 12.0 ng/mL, P = .008). The increase in 25(OH)VitD levels in the simvastatin 40 mg group was significantly greater compared to that in the simvastatin/ezetimibe 10/10 mg group (P = .04). Both groups exhibited similar reductions in low-density lipoprotein cholesterol (LDL-C) levels.
  
  
  CONCLUSIONS
  For similar LDL-C lowering simvastatin 40 mg is associated with greater increase in 25(OH)VitD compared to simvastatin/ezetimibe 10/10 mg. Whether this difference is relevant in terms of CVD risk reduction is unknown.
authors.affiliation: Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. vaglimp@yahoo.com
authors.forename: Evangelos N
authors.initials: EN
authors.lastname: Liberopoulos
authors.forename: Stefania E
authors.initials: SE
authors.lastname: Makariou
authors.forename: Elisavet
authors.initials: E
authors.lastname: Moutzouri
authors.forename: Mixalis S
authors.initials: MS
authors.lastname: Kostapanos
authors.forename: Anna
authors.initials: A
authors.lastname: Challa
authors.forename: Moses
authors.initials: M
authors.lastname: Elisaf
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000097:blood*; D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use*; D002112:Calcifediol / Q000097:blood*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use; D006115:Greece / Q000453:epidemiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D049990:Membrane Transport Modulators / Q000009:adverse effects / Q000627:therapeutic use; D026901:Membrane Transport Proteins; D008875:Middle Aged; D012306:Risk; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects*; D014808:Vitamin D Deficiency / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D005765:Gastrointestinal Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008565:Membrane Proteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D015652:25-Hydroxyvitamin D 2; D019821:Simvastatin; D002112:Calcifediol