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

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

• References

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