Efficacy, safety, tolerability, and pharmacokinetic profile of evacetrapib administered as monotherapy or in combination with atorvastatin in Japanese patients with dyslipidemia.
The cholesteryl ester transfer protein (CETP) inhibitor evacetrapib has been previously shown to increase high-density lipoprotein cholesterol (HDL-C) and decrease low-density lipoprotein cholesterol (LDL-C) levels, as monotherapy or in combination with statins. In this study, 165 Japanese patients with elevated LDL-C or low HDL-C levels were randomly assigned to receive placebo, evacetrapib monotherapy 30 mg, 100 mg, or 500 mg, atorvastatin 10 mg, or evacetrapib 100 mg in combination with atorvastatin 10 mg. After 12 weeks, evacetrapib monotherapy increased HDL-C levels by 74%, 115%, and 136% and decreased LDL-C levels by 15%, 23%, and 22% and CETP activity by 50%, 83%, and 95% (for the 30-mg, 100-mg, and 500-mg dose groups, respectively) versus placebo. In combination with atorvastatin 10 mg, evacetrapib 100 mg increased HDL-C levels by 103% and decreased LDL-C levels by 15% and CETP activity by 68% versus atorvastatin alone. After a 4- to 6-week washout, HDL-C, LDL-C, and CETP mass and activity returned to baseline levels in the evacetrapib-treated groups, and most patients had evacetrapib concentrations below the quantitation limit. Evacetrapib monotherapy or in combination with atorvastatin was not likely to be associated with any significant change in blood pressure and did not have any adverse effects on mineralocorticoid or glucocorticoid measures. Notably, plasma evacetrapib concentrations were mostly undetectable, and all pharmacodynamic biomarkers (HDL-C and LDL-C levels and CETP mass and activity) returned to baseline after a 4- to 6-week washout. In conclusion, evacetrapib as monotherapy or in combination with atorvastatin effectively decreased CETP activity and LDL-C levels and increased HDL-C levels after 12 weeks in Japanese patients with dyslipidemia.
Teramoto T
，Takeuchi M
，Morisaki Y
，Ruotolo G
，Krueger KA
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Nigella sativa (black seed) effects on plasma lipid concentrations in humans: A systematic review and meta-analysis of randomized placebo-controlled trials.
The effects of Nigella sativa (NS) on plasma lipid concentrations are controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to obtain a conclusive result in humans. PubMed-Medline, SCOPUS, Web of Science, and Google Scholar databases were searched (up to August 2015) to identify RCTs investigating the impact of NS on total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and triglycerides concentrations. A random-effects model and the generic inverse variance weighting method were used for quantitative data synthesis. Meta-regression, sensitivity analysis, and publication bias assessments were performed using standard methods. A total of 17 RCTs examining the effects of NS on plasma lipid concentrations were included. Meta-analysis suggested a significant association between NS supplementation and a reduction in total cholesterol (weighed-mean-difference [WMD]: -15.65mg/dL, 95% CI: -24.67, -6.63, p=0.001), LDL-C (WMD: -14.10mg/dL, 95% CI: -19.32, -8.88, p<0.001), and triglyceride levels (WMD: -20.64mg/dL, 95% CI: -30.29, -11.00, p<0.001). No significant effect on HDL-C concentrations (WMD: 0.28mg/dL, 95% CI: -1.96, 2.53, p=0.804) was found. A greater effect of NS seed oil versus seed powder was observed on serum total cholesterol and LDL-C levels, and an increase in HDL-C levels was found only after NS seed powder supplementation. NS has a significant impact on plasma lipid concentrations, leading to lower total cholesterol, LDL-C, and TG levels while increased HDL-C is associated with NS powder only. Further RCTs are needed to explore the NS benefits on cardiovascular outcomes.
Sahebkar A
，Beccuti G
，Simental-Mendía LE
，Nobili V
，Bo S
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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
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