TY - JOUR
T1 - Statin therapy reduces plasma endothelin-1 concentrations: A meta-analysis of 15 randomized controlled trials
AU - Sahebkar, Amirhossein
AU - Kotani, Kazuhiko
AU - Serban, Corina
AU - Ursoniu, Sorin
AU - Mikhailidis, Dimitri P.
AU - Jones, Steven R.
AU - Ray, Kausik K.
AU - Blaha, Michael J.
AU - Rysz, Jacek
AU - Toth, Peter P.
AU - Muntner, Paul
AU - Lip, Gregory Y.h.
AU - Banach, Maciej
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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 – WMD: −0.27 pg/mL, 95%CI: −0.49, −0.05; p = 0.01; >40 mg/day – WMD: −0.38 pg/mL, 95%CI: −0.68, −0.08; p = 0.01). Lipophilic (atorvastatin, simvastatin, fluvastatin, and cerivastatin – WMD: −0.34 pg/mL, 95%CI: −0.55, −0.13; p < 0.01), but not a hydrophilic statin (pravastatin – 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.
AB - 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 – WMD: −0.27 pg/mL, 95%CI: −0.49, −0.05; p = 0.01; >40 mg/day – WMD: −0.38 pg/mL, 95%CI: −0.68, −0.08; p = 0.01). Lipophilic (atorvastatin, simvastatin, fluvastatin, and cerivastatin – WMD: −0.34 pg/mL, 95%CI: −0.55, −0.13; p < 0.01), but not a hydrophilic statin (pravastatin – 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.
U2 - 10.1016/j.atherosclerosis.2015.05.022
DO - 10.1016/j.atherosclerosis.2015.05.022
M3 - Article
SN - 0021-9150
VL - 241
SP - 433
EP - 442
JO - Atherosclerosis
JF - Atherosclerosis
IS - 2
ER -