title: Randomized controlled trial assessing the effect of simvastatin in primary biliary cirrhosis.
abstract: BACKGROUND
  This study evaluated the effect of statins in Primary biliary cirrhosis (PBC) on endothelial function, anti-oxidant status and vascular compliance.
  
  
  METHODS
  Primary biliary cirrhosis patients with hypercholesterolaemia were randomized to receive 20 mg simvastatin or placebo in a single blind, randomized controlled trial. Body mass index, blood pressure, glucose, liver function, lipid profile, immunoglobulin levels, serological markers of endothelial function and anti-oxidant status were measured as well as vascular compliance, calculated from pulse wave analysis and velocity, at recruitment and again at 3, 6, 9 and 12 months.
  
  
  RESULTS
  Twenty-one PBC patients (F = 20, mean age = 55) were randomized to simvastatin 20 mg (n = 11) or matched placebo (n = 10). At completion of the trial, serum cholesterol levels in the simvastatin group were significantly lower compared with the placebo group (4.91 mmol/L vs. 6.15 mmol/L, P = 0.01). Low-density lipoprotein (LDL) levels after 12 months were also significantly lower in the simvastatin group (2.33 mmol/L vs. 3.53 mmol/L, P = 0.01). After 12 months of treatment, lipid hydroperoxides were lower (0.49 μmol/L vs. 0.59 μmol/L, P = 0.10) while vitamin C levels were higher (80.54 μmol/L vs. 77.40 μmol/L, P = 0.95) in the simvastatin group. Pulse wave velocity remained similar between treatment groups at 12 months (8.45 m/s vs. 8.80 m/s, P = 0.66). Only one patient discontinued medication owing to side effects. No deterioration in liver transaminases was noted in the simvastatin group.
  
  
  CONCLUSIONS
  Statin therapy in patients with PBC appears safe and effective towards overall reductions in total cholesterol and LDL levels. Our initial study suggests that simvastatin may also confer advantageous effects on endothelial function and antioxidant status.
authors.affiliation: Department of Hepatology (Liver Unit), Royal Victoria Hospital, Belfast, UK. johnny.cash@belfasttrust.hscni.net
authors.forename: William J
authors.initials: WJ
authors.lastname: Cash
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Neill
authors.forename: Mark E
authors.initials: ME
authors.lastname: O'Donnell
authors.forename: David R
authors.initials: DR
authors.lastname: McCance
authors.forename: Ian S
authors.initials: IS
authors.lastname: Young
authors.forename: Jane
authors.initials: J
authors.lastname: McEneny
authors.forename: Neil I
authors.initials: NI
authors.lastname: McDougall
authors.forename: Michael E
authors.initials: ME
authors.lastname: Callender
mesh_terms: D001205:Ascorbic Acid / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy; D018836:Inflammation Mediators / Q000097:blood; D008054:Lipid Peroxides / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009660:Northern Ireland; D063177:Pulse Wave Analysis; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000187:drug effects
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D002784:Cholesterol; D019821:Simvastatin; D001205:Ascorbic Acid
keywords: antioxidant; endothelial function; primary biliary cirrhosis; randomized controlled trial; safety; simvastatin