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

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: -0.30 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. 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.

Sahebkar A ，Kotani K ，Serban C ，Ursoniu S ，Mikhailidis DP ，Jones SR ，Ray KK ，Blaha MJ ，Rysz J ，Toth PP ，Muntner P ，Lip GY ，Banach M ，Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group ... -  《-》

A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials investigating the effects of statin therapy on plasma lipid concentrations in HIV-infected patients.

Statin therapy may lower plasma lipid concentrations, but the evidence in HIV-infected patients is still unclear. Therefore, we aimed to investigate the impact of statin therapy on plasma lipid concentrations through a systematic review of the literature and meta-analysis of available randomized controlled trials (RCTs). The literature search included PUBMED, SCOPUS, Web of Science and Google Scholar up to October 30, 2015. The meta-analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Two investigators independently reviewed the title or abstract, further reviewed the full-texts and extracted information on study characteristics and study outcomes. Meta-analysis of 12 RCTs with 697 participants suggested significant reductions in plasma concentrations of low density lipoprotein (LDL) cholesterol (WMD: -0.72mmol/L [-27.8mg/dL], 95%CI: -1.04, -0.39, p<0.001; I(2)=85.7%), total cholesterol (WMD: -1.03mmol/L [-39.8mg/dL], 95%CI: -1.42, -0.64, p<0.001; I(2)=94.7%) and non-high density lipoprotein cholesterol (non-HDL-C) (WMD: -0.81mmol/L [-31.3mg/dl], 95%CI: -1.32, -0.30, p=0.002; I(2)=76.5%), and elevations in HDL-C (WMD: 0.072mmol/L [2.8mg/dL], 95%CI: 0.053, 0.092, p<0.001; I(2)=0%) following treatment with statins (mostly of moderate-intensity). No significant alteration in plasma triglycerides (TG) concentrations was found (WMD: -0.16mmol/L [-14.2mg/dL], 95%CI: -0.61, 0.29, p=0.475; I(2)=90.2%). All these effects were robust in sensitivity analysis, suggesting that the computed effect is not driven by any single study. In subgroup analysis, no significant difference was found among different statins in terms of changing plasma concentrations of LDL-C, HDL-C and TG. However, atorvastatin was found to be more efficacious in reducing plasma total cholesterol concentrations (p<0.001). In conclusion, the meta-analysis suggested significant reductions in plasma concentrations of LDL-C, total cholesterol and non-HDL-C, and elevations in HDL-C, but no significant alteration in plasma TG following treatment with statins.

Banach M ，Dinca M ，Ursoniu S ，Serban MC ，Howard G ，Mikhailidis DP ，Nicholls S ，Lip GYH ，Glasser S ，Martin SS ，Muntner P ，Rysz J ，Toth PP ，Sahebkar A ，Lipid Blood Pressure Meta-analysis Collaboration Group ... -  《-》

Association between statin use and plasma D-dimer levels. A systematic review and meta-analysis of randomised controlled trials.

Sahebkar A ，Serban C ，Mikhailidis DP ，Undas A ，Lip GY ，Muntner P ，Bittner V ，Ray KK ，Watts GF ，Hovingh GK ，Rysz J ，Kastelein JJ ，Banach M ，Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group ... -  《-》

Impact of statin therapy on plasma resistin and visfatin concentrations: A systematic review and meta-analysis of controlled clinical trials.

The beneficial effects of statin therapy in reducing cardiovascular morbidity and mortality is not merely explained by the lipid-modulating effects. Although adipokines levels have been associated with cardiometabolic disorders, a few studies have explored the effect of statin on resistin and visfatin. We aimed to evaluate the impact of statin therapy on levels of resistin and visfatin through a meta-analysis of published studies. A systematic literature search in Medline and SCOPUS databases was conducted up to January 2015 to identify controlled trials assessing changes in plasma concentrations of visfatin and resistin during treatment with statins. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. 12 eligible studies with 14 treatment arms were included. Overall, 844 participants were studied. No significant change in plasma resistin concentrations was observed following statin therapy (WMD: -0.11ng/mL, CI: -1.94,1.73, p=0.909). This effect was robust and not affected by statin type, treatment duration and LDL-cholesterol concentrations. With respect to visfatin concentrations, there was a marginally significant reduction following statin therapy (WMD: -2.40ng/mL, CI: -4.79,-0.002, p=0.050). However, this effect size was weak and sensitive to three of the trials included in the analysis. This meta-analysis did not suggest any effect of statin therapy on plasma resistin levels, while a slight reduction in visfatin levels was found. The effect of statins on visfatin levels may represent a novel pleiotropic characteristic of these drugs.

Sahebkar A ，Giorgini P ，Ludovici V ，Pedone C ，Ferretti G ，Bacchetti T ，Grassi D ，Di Giosia P ，Ferri C ... -  《-》

Statin therapy and plasma coenzyme Q10 concentrations--A systematic review and meta-analysis of placebo-controlled trials.

Statin therapy may lower plasma coenzyme Q10 (CoQ10) concentrations, but the evidence as to the significance of this effect is unclear. We assessed the impact of statin therapy on plasma CoQ10 concentrations through the meta-analysis of available RCTs. The literature search included selected databases up to April 30, 2015. The meta-analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The data from 8 placebo-controlled treatment arms suggested a significant reduction in plasma CoQ10 concentrations following treatment with statins (WMD: -0.44 μmol/L, 95%CI: -0.52, -0.37, p<0.001). The pooled effect size was robust and remained significant in the leave-one-out sensitivity analysis. Subgroup analysis suggested that the impact of statins on plasma CoQ10 concentrations is significant for all 4 types of statins studied i.e. atorvastatin (WMD: -0.41 μmol/L, 95%CI: -0.53, -0.29, p<0.001), simvastatin (WMD: -0.47 μmol/L, 95% CI: -0.61, -0.33, p<0.001), rosuvastatin (WMD: -0.49 μmol/L, 95%CI: -0.67, -0.31, p<0.001) and pravastatin (WMD: -0.43 μmol/L, 95%CI: -0.69, -0.16, p=0.001). Likewise, there was no differential effect of lipophilic (WMD: -0.43 μmol/L, 95%CI: -0.53, -0.34, p<0.001) and hydrophilic statins (WMD: -0.47 μmol/L, 95%CI: -0.62, -0.32, p<0.001). With respect to treatment duration, a significant effect was observed in both subsets of trials lasting <12 weeks (WMD: -0.51 μmol/L, 95%CI: -0.64, -0.39, p<0.001) and ≥12 weeks (WMD: -0.40 μmol/L, 95%CI: -0.50, -0.30, p<0.001). The meta-analysis showed a significant reduction in plasma CoQ10 concentrations following treatment with statins. Further well-designed trials are required to confirm our findings and elucidate their clinical relevance.

Banach M ，Serban C ，Ursoniu S ，Rysz J ，Muntner P ，Toth PP ，Jones SR ，Rizzo M ，Glasser SP ，Watts GF ，Blumenthal RS ，Lip GY ，Mikhailidis DP ，Sahebkar A ，Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group ... -  《-》