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

Objective: 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. Methods and results: 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: -0.30 pg/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: -0.51 pg/mL, 95% CI: -0.89, -0.14, p < 0.01; > 12 week - WMD: -0.19 pg/mL, 95% CI: -0.36, -0.02; p < 0.05) or by dose of statins (< 40 mg/day e WMD: -0.27 pg/mL, 95% CI: -0.49, -0.05; p = 0.01; > 40 mg/day e WMD: -0.38 pg/mL, 95% CI: -0.68, -0.08; p = 0.01). Lipophilic (atorvastatin, simvastatin, fluvastatin, and cerivastatin e WMD: -0.34 pg/mL, 95% CI: -0.55, -0.13; p < 0.01), but not a hydrophilic statin (pravastatin e WMD: -0.18 pg/mL, 95% CI: -0.44 -0.08; p > 0.05) had a significant effect in promoting ET-1 reduction. Conclusions: 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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.