The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low-Density Lipoprotein Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Background. Elevated plasma low-density lipoprotein cholesterol (LDL-C) is the main risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins are the drugs of choice for decreasing LDL-C and are used for the prevention and management of ASCVD. Guidelines recommend that subjects with hi...
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doaj-feee0207039a4f40af1acbbc173ec34d2021-09-20T00:30:33ZengHindawi LimitedMediators of Inflammation1466-18612021-01-01202110.1155/2021/9661752The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low-Density Lipoprotein Levels: A Systematic Review and Meta-Analysis of Randomized Controlled TrialsTannaz Jamialahmadi0Fatemeh Baratzadeh1Željko Reiner2Luis E. Simental-Mendía3Suowen Xu4Andrey V. Susekov5Raul D. Santos6Amirhossein Sahebkar7Department of Food Science and TechnologySchool of PharmacyDepartment of Internal MedicineBiomedical Research UnitDivision of Life Sciences and MedicineGBOU DPO Russian Medical Academy for Postgraduate Medical Education Ministry of HealthLipid Clinic Heart Institute (Incor)Biotechnology Research CenterBackground. Elevated plasma low-density lipoprotein cholesterol (LDL-C) is the main risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins are the drugs of choice for decreasing LDL-C and are used for the prevention and management of ASCVD. Guidelines recommend that subjects with high and very high ASCVD risk should be treated with high-intensity statins or a combination of high-intensity statins and ezetimibe. The lipophilicity or hydrophilicity (solubility) of statins is considered to be important for at least some of their LDL-C lowering independent pleiotropic effects. Oxidative modification of LDL (ox-LDL) is considered to be the most important atherogenic modification of LDL and is supposed to play a crucial role in atherogenesis and ASCVD outcomes. Objective. The aim of this systematic review and meta-analysis was to find out what are the effects of statin intensity, lipophilicity, and combination of statins plus ezetimibe on ox-LDL. Methods. PubMed, Scopus, Embase, and Web of Science were searched from inception to February 5, 2021, for randomized controlled trials (RCTs). Two independent and blinded authors evaluated eligibility by screening the titles and abstracts of the studies. Risk of bias in the studies included in this meta-analysis was evaluated according to the Cochrane instructions. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. Evaluation of funnel plot, Begg’s rank correlation, and Egger’s weighted regression tests were used to assess the presence of publication bias. Results. Among the 1427 published studies identified by a systematic databases search, 20 RCTs were finally included in the systematic review and meta-analysis. A total of 1874 patients are included in this meta-analysis. This meta-analysis suggests that high-intensity statin treatment is associated with a significant decrease in circulating concentrations of ox-LDL when compared with low-to-moderate treatment (SMD: -0.675, 95% CI: -0.994, -0.357, p<0.001; I2: 55.93%). There was no difference concerning ox-LDL concentration between treatments with hydrophilic and lipophilic statins (SMD: -0.129, 95% CI: -0.330, -0.071, p=0.206; I2: 45.3%), but there was a significant reduction in circulating concentrations of ox-LDL associated with statin plus ezetimibe combination therapy when compared with statin monotherapy (SMD: -0.220, 95% CI: -0.369, -0.071, p=0.004; I2: 0%). Conclusion. High-dose statin or combination of statins with ezetmibe reduces plasma ox-LDL in comparison low-to-moderate intensity statin therapy alone. Statin lipophilicity is not associated with reduction in ox-LDL plasma concentrations.http://dx.doi.org/10.1155/2021/9661752 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tannaz Jamialahmadi Fatemeh Baratzadeh Željko Reiner Luis E. Simental-Mendía Suowen Xu Andrey V. Susekov Raul D. Santos Amirhossein Sahebkar |
spellingShingle |
Tannaz Jamialahmadi Fatemeh Baratzadeh Željko Reiner Luis E. Simental-Mendía Suowen Xu Andrey V. Susekov Raul D. Santos Amirhossein Sahebkar The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low-Density Lipoprotein Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Mediators of Inflammation |
author_facet |
Tannaz Jamialahmadi Fatemeh Baratzadeh Željko Reiner Luis E. Simental-Mendía Suowen Xu Andrey V. Susekov Raul D. Santos Amirhossein Sahebkar |
author_sort |
Tannaz Jamialahmadi |
title |
The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low-Density Lipoprotein Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials |
title_short |
The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low-Density Lipoprotein Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials |
title_full |
The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low-Density Lipoprotein Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials |
title_fullStr |
The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low-Density Lipoprotein Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials |
title_full_unstemmed |
The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low-Density Lipoprotein Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials |
title_sort |
effects of statin dose, lipophilicity, and combination of statins plus ezetimibe on circulating oxidized low-density lipoprotein levels: a systematic review and meta-analysis of randomized controlled trials |
publisher |
Hindawi Limited |
series |
Mediators of Inflammation |
issn |
1466-1861 |
publishDate |
2021-01-01 |
description |
Background. Elevated plasma low-density lipoprotein cholesterol (LDL-C) is the main risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins are the drugs of choice for decreasing LDL-C and are used for the prevention and management of ASCVD. Guidelines recommend that subjects with high and very high ASCVD risk should be treated with high-intensity statins or a combination of high-intensity statins and ezetimibe. The lipophilicity or hydrophilicity (solubility) of statins is considered to be important for at least some of their LDL-C lowering independent pleiotropic effects. Oxidative modification of LDL (ox-LDL) is considered to be the most important atherogenic modification of LDL and is supposed to play a crucial role in atherogenesis and ASCVD outcomes. Objective. The aim of this systematic review and meta-analysis was to find out what are the effects of statin intensity, lipophilicity, and combination of statins plus ezetimibe on ox-LDL. Methods. PubMed, Scopus, Embase, and Web of Science were searched from inception to February 5, 2021, for randomized controlled trials (RCTs). Two independent and blinded authors evaluated eligibility by screening the titles and abstracts of the studies. Risk of bias in the studies included in this meta-analysis was evaluated according to the Cochrane instructions. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. Evaluation of funnel plot, Begg’s rank correlation, and Egger’s weighted regression tests were used to assess the presence of publication bias. Results. Among the 1427 published studies identified by a systematic databases search, 20 RCTs were finally included in the systematic review and meta-analysis. A total of 1874 patients are included in this meta-analysis. This meta-analysis suggests that high-intensity statin treatment is associated with a significant decrease in circulating concentrations of ox-LDL when compared with low-to-moderate treatment (SMD: -0.675, 95% CI: -0.994, -0.357, p<0.001; I2: 55.93%). There was no difference concerning ox-LDL concentration between treatments with hydrophilic and lipophilic statins (SMD: -0.129, 95% CI: -0.330, -0.071, p=0.206; I2: 45.3%), but there was a significant reduction in circulating concentrations of ox-LDL associated with statin plus ezetimibe combination therapy when compared with statin monotherapy (SMD: -0.220, 95% CI: -0.369, -0.071, p=0.004; I2: 0%). Conclusion. High-dose statin or combination of statins with ezetmibe reduces plasma ox-LDL in comparison low-to-moderate intensity statin therapy alone. Statin lipophilicity is not associated with reduction in ox-LDL plasma concentrations. |
url |
http://dx.doi.org/10.1155/2021/9661752 |
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