title: Impact of fibrate therapy on plasma plasminogen activator inhibitor-1: a systematic review and meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  The aim of this systematic review was to perform a meta-analysis of randomized controlled trials (RCTs) examining the efficacy of fibrate therapy in reducing plasma concentration or activity of plasminogen activator inhibitor 1 (PAI-1).
  
  
  METHODS
  Scopus and MEDLINE databases were searched (up to October 15, 2014) to identify RCTs investigating whether fibrates lower plasma PAI-1 concentration or activity. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed to assess the impact of potential moderators on the estimated effect sizes.
  
  
  RESULTS
  A total of 14 RCTs examining the effects of gemfibrozil (6 trials), bezafibrate (4 trials), and fenofibrate (5 trials) were included. Meta-analysis suggested that fibrate therapy did not significantly reduce plasma PAI-1 concentration (weighed mean difference [WMD]: -11.39 ng/mL, 95% CI: -26.64, 3.85, p=0.143) or activity (WMD: 2.02 U/mL, 95% CI: -0.87, 4.90, p=0.170). These results remained unchanged after subgroup analysis according to duration of treatment (<12 and ≥12 weeks) and type of fibrate administered (fenofibrate, bezafibrate or gemfibrozil). The estimated effects of fibrate therapy on plasma concentration and activity of PAI-1 were independent of treatment duration and changes in plasma triglyceride levels in the meta-regression analysis.
  
  
  CONCLUSIONS
  This meta-analysis of RCTs suggested that fibrate therapy does not reduce plasma concentration or activity of PAI-I. The putative benefits of fibrate therapy in patients with cardiovascular disease appear to be exerted via mechanisms independent of effects on PAI-1.
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
authors.affiliation: Biomedical Research Unit, Mexican Social Security Institute, Durango, Mexico. Electronic address: luis_simental81@hotmail.com.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Simental-Mendía
authors.affiliation: Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University Townsville, QLD 4811, Australia; Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, QLD 4814, Australia. Electronic address: jonathan.golledge@jcu.edu.au.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
mesh_terms: D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D015536:Down-Regulation; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D058607:Fibric Acids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D058607:Fibric Acids; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human
keywords: Coronary heart disease; Fibric acid; Peroxisome proliferator-activated receptor; Plasminogen; Thrombosis