title: A Systematic Review and Meta-Analysis of Controlled Trials on the Effects of Statin and Fibrate Therapies on Plasma Homocysteine Levels.
abstract: BACKGROUND
  Plasma homocysteine is an independent non-traditional risk factor for atherosclerotic cardiovascular disease. The impact of statin therapy on plasma homocysteine is not conclusive.
  
  
  OBJECTIVE
  To evaluate the effect of statin therapy on plasma homocysteine concentrations in a systematic review and meta-analysis of controlled clinical trials. The secondary aim was to assess the comparative effect of statins versus fibrates on plasma homocysteine levels in head-to-head trials.
  
  
  METHODS
  PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched (from the first reports to March 07, 2016) to identify controlled trials evaluating the impact of statins on plasma homocysteine concentrations. A systematic assessment of bias in the included studies was performed using the Cochrane criteria. A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. Random-effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of potential moderators.
  
  
  RESULTS
  Meta-analysis of data from 7 studies did not suggest a significant alteration in plasma homocysteine concentrations following treatment with statins compared with the control group (WMD: -0.59 μmol/L, 95% CI: -1.66, 0.48, p=0.279; I2=52.53%). However, meta-analysis of 9 studies suggested a significantly greater reduction of plasma homocysteine concentrations with statins compared with fenofibrate (WMD: -4.81 μmol/L, 95% CI: -5.39, -4.23, p<0.001; I2=0%). Results of both analyses were robust in the sensitivity analysis.
  
  
  CONCLUSIONS
  Statin therapy is not associated with a significant alteration of plasma homocysteine levels, while fenofibrate increases the homocysteine levels when compared with statins.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
authors.forename: Matteo
authors.initials: M
authors.lastname: Pirro
authors.forename: Željko
authors.initials: Ž
authors.lastname: Reiner
authors.forename: Arrigo
authors.initials: A
authors.lastname: Cicero
authors.forename: Gianna
authors.initials: G
authors.lastname: Ferretti
authors.forename: Mario
authors.initials: M
authors.lastname: Simental-Mendía
authors.affiliation: Canoas 100, Col. Los Angeles 34067, Durango, Dgo., Mexico.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Simental-Mendía
mesh_terms: D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy; D018849:Controlled Clinical Trials as Topic / Q000379:methods*; D058607:Fibric Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D058607:Fibric Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006710:Homocysteine