Statin therapy reduces plasma endothelin-1 concentrations: A meta-analysis of 15 randomized controlled trials.

Abstract

Raised plasma endothelin-1 (ET-1) levels may be a risk factor for vascular dysfunction and cardiovascular (CV) disease. This meta-analysis assessed the effect of statins on circulating ET-1 concentrations. The search included PUBMED, Cochrane Library, Web of Science, Scopus, and EMBASE up to September 30, 2014 to identify randomized controlled trials (RCTs) with ET-1 measurement during statin therapy. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. Data from 15 RCTs showed that statin therapy significantly reduces plasma ET-1 concentrations (WMD:-0.30pg/mL, 95%CI:-0.47,-0.13; p<0.01). This effect was robust in sensitivity analysis, and not largely affected by the duration of statin therapy (<12 weeks - WMD:-0.51pg/mL, 95%CI:-0.89,-0.14, p<0.01; >12 week -WMD:-0.19pg/mL, 95%CI:-0.36,-0.02; p<0.05) or by dose of statins (<40mg/day - WMD:-0.27pg/mL, 95%CI:-0.49,-0.05; p=0.01; >40mg/day - WMD:-0.38pg/mL, 95%CI:-0.68,-0.08; p=0.01). Lipophilic (atorvastatin, simvastatin, fluvastatin, and cerivastatin - WMD:-0.34pg/mL, 95%CI:-0.55,-0.13; p<0.01), but not a hydrophilic statin (pravastatin - WMD:-0.18pg/mL, 95%CI:-0.44-0.08; p>0.05) had a significant effect in promoting ET-1 reduction. Statin therapy significantly reduces circulating ET-1 concentrations, regardless of treatment duration or dose of statins. This effect of statins may be influenced by statin lipophilicity. There is a need to establish whether lowering ET-1 levels has a beneficial effect on CV events.