title: Impact of statin therapy on plasma levels of plasminogen activator inhibitor-1. A systematic review and meta-analysis of randomised controlled trials.
abstract: Elevated plasma levels of the pro-thrombotic and pro-inflammatory factor plasminogen activator inhibitor-1 (PAI-1) may contribute to the pathogenesis of atherosclerotic cardiovascular disease. Beyond their lipid-lowering effect, statins have been shown to modulate plasma PAI-1 levels but evidence from individual randomised controlled trials (RCTs) is controversial. Therefore, we aimed to assess the potential effects of statin therapy on plasma PAI-1 concentration through a meta-analysis of RCTs. We searched Medline and SCOPUS databases (up to October 3, 2014) to identify RCTs investigating the effect of statin therapy on plasma PAI-1 concentrations. We performed random-effects meta-analysis and assessed heterogeneity (I² test, subgroup and sensitivity analyses) and publication bias (funnel plot, Egger and "trim and fill" tests). Sixteen RCTs (comprising 19 treatment arms) were included and pooled analyses showed a significant effect of statins in reducing plasma PAI-1 concentrations (weighted mean difference WMD: -15.72 ng/ml, 95 % confidence interval [CI]: -25.01, -6.43,). In subgroup analysis, this effect remained significant in with lipophilic statins (atorvastatin and simvastatin) (WMD: -21.32 ng/ml, 95 % CI: -32.73, -9.91, I²=99 %) and particularly atorvastatin (WMD: -20.88 ng/mL, 95 % CI: -28.79, -12.97, I2=97 %). In the meta-regression analysis, the impact of statins on PAI-1 did not correlate with the administered dose, duration of treatment and changes in plasma LDL-cholesterol concentrations. Finally, evidence of publication bias was observed. In conclusion, taking into account the limit of heterogeneity between studies, the present meta-analysis suggests that statin therapy (mainly atorvastatin) significantly lowers plasma PAI-1 concentrations.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
authors.forename: Cristiana
authors.initials: C
authors.lastname: Catena
authors.forename: Kausik K
authors.initials: KK
authors.lastname: Ray
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Vallejo-Vaz
authors.forename: Željko
authors.initials: Ž
authors.lastname: Reiner
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Sechi
authors.affiliation: GianLuca Colussi, MD, Clinica Medica, University of Udine, University Hospital, Building 8, 1st floor, 33100 Udine, Italy, Tel.: +39 0432 559 804, Fax: +39 0432 559 490, E-mail: gianluca.colussi@uniud.it.
authors.forename: GianLuca
authors.initials: G
authors.lastname: Colussi
mesh_terms: D000069059:Atorvastatin / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D000069059:Atorvastatin
keywords: Plasminogen activator inhibitor-1; atherosclerosis; cardiovascular disease; hypolipidaemic agents; meta-analysis