title: High-dose statin monotherapy versus low-dose statin/ezetimibe combination on fasting and postprandial lipids and endothelial function in obese patients with the metabolic syndrome: The PANACEA study.
abstract: BACKGROUND
  Low-dose statin therapy in combination with ezetimibe, an inhibitor of intestinal cholesterol absorption, lowers plasma LDL-cholesterol levels to a similar degree as high-dose statin monotherapy. This study assessed whether similar LDL-cholesterol lowering with simvastatin/ezetimibe combination therapy improves fasting and postprandial arterial endothelial function compared to high-dose statin therapy alone.
  
  
  METHODS
  Multicenter, double-blind, crossover trial in 100 abdominally obese patients with the metabolic syndrome, randomized to 6 weeks' treatment with simvastatin 80 mg or simvastatin/ezetimibe 10/10 mg. Flow mediated dilatation (FMD) and peripheral arterial tonometry (EndoPAT) as well as plasma lipids were measured in the fasting state and after an oral lipid load at baseline and after both treatments.
  
  
  RESULTS
  Fasting LDL-cholesterol levels (3.57 mmol/L at baseline) were reduced to 1.79 mmol/L following treatment with simvastatin 80 mg and 1.81 mmol/L with simvastatin/ezetimibe 10/10 mg, respectively. Plasma lipids were similar at 4 h after an oral lipid load following both treatments for 6 weeks. Fasting endothelial function was also similar with both treatments when assessed by FMD (adjusted mean ± SE: 4.35 ± 0.19 vs. 4.43 ± 0.18; P = 0.777) and EndoPAT (2.12 ± 0.05 vs 2.20 ± 0.05; P = 0.304). After an oral fat load, changes in endothelial function were also comparable for both treatments as assessed by FMD (-0.34 ± 0.21 vs. -0.43 ± 0.20; P = 0.766) and EndoPAT (0.00 ± 0.07 vs. -0.04 ± 0.08; P = 0.712).
  
  
  CONCLUSIONS
  Treatment with simvastatin/ezetimibe 10/10 mg induced no difference in endothelial function in the fasting and postprandial state compared to simvastatin 80 mg while attaining similar LDL-c levels in obese patients with metabolic syndrome.
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Westerink
authors.forename: John E
authors.initials: JE
authors.lastname: Deanfield
authors.forename: Ben P
authors.initials: BP
authors.lastname: Imholz
authors.forename: Wilko
authors.initials: W
authors.lastname: Spiering
authors.forename: Dick C
authors.initials: DC
authors.lastname: Basart
authors.forename: Blai
authors.initials: B
authors.lastname: Coll
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Frank L J
authors.initials: FL
authors.lastname: Visseren
mesh_terms: D000328:Adult; D000368:Aged; D001384:Azetidines / Q000008:administration & dosage*; D004311:Double-Blind Method; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D000069499:Ezetimibe, Simvastatin Drug Combination; D005215:Fasting; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008055:Lipids / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000150:complications; D019821:Simvastatin / Q000008:administration & dosage*
chemical_list: D001384:Azetidines; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D019821:Simvastatin