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Thromb Haemost 2016; 116(01): 162-171
DOI: 10.1160/TH15-10-0770
Atherosclerosis and Ischaemic Disease
Schattauer GmbH

Impact of statin therapy on plasma levels of plasminogen activator inhibitor-1

A systematic review and meta-analysis of randomised controlled trials
Amirhossein Sahebkar
1   Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
2   Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia
,
Cristiana Catena
3   Clinica Medica, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy
,
Kausik K. Ray
4   Department of Public Health and Primary Care, School of Public Health, Imperial College London, UK
,
Antonio J. Vallejo-Vaz
4   Department of Public Health and Primary Care, School of Public Health, Imperial College London, UK
,
Željko Reiner
5   University Hospital Centre Zagreb, School of Medicine University of Zagreb, Department of Internal Medicine, Zagreb, Croatia
,
Leonardo A. Sechi
3   Clinica Medica, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy
,
GianLuca Colussi
3   Clinica Medica, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy
› Author Affiliations
Further Information

Publication History

Received: 02 October 2015

Accepted after major revision: 28 February 2016

Publication Date:
27 November 2017 (online)

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Summary

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.

Keywords

Plasminogen activator inhibitor-1 - hypolipidaemic agents - atherosclerosis - cardiovascular disease - meta-analysis

 

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