RELATIONSHIP BETWEEN LOW-DENSITY LIPOPROTEIN CHOLESTEROL, LIPID LOWERING AGENTS AND THE RISK OF STROKE: A META-ANALYSIS OF OBSERVATIONAL STUDIES AND RANDOMIZED CONTROLLED TRIALS

Background: Many patients with hypercholesterolemia and/or cardiovascular disease are unable to achieve sufficient low-density lipoprotein cholesterol (LDL-C) reduction with statins alone (or are statin intolerant). This is increasingly the case with clinical guidelines recommending that lower LDL-C levels are beneficial for patients. This network meta-analysis (NMA) assessed the relative efficacy of lipid lowering therapies (LLTs) added to statins for reducing LDL-C. Methods: A systematic review of randomized controlled clinical trials to May 2020 identified 48 studies for inclusion in the primary NMA. The primary NMA included studies ≥12 weeks duration in which alirocumab, bempedoic acid, evolocumab, ezetimibe, or inclisiran were added to moderate-high intensity statins (or lower intensity / no statin in statin intolerant patients). Random effects NMA was used to analyse % change in LDL-C to compare the treatment effects indirectly. Results: Over 12 weeks, all non-statin LLTs significantly reduced LDL-C from baseline versus placebo. Evolocumab 140 mg Q2W / 420 mg QM and alirocumab 150 mg Q2W were associated with largest LDL-C reductions, which were greater than those achieved with lower/alternative doses of alirocumab, bempedoic acid (± ezetimibe), ezetimibe and inclisiran (Table). Consistent results were observed in sensitivity analyses to address heterogeneity (excluding familial hypercholesterolemia and east Asian studies), in the subgroup NMA of studies in predominantly atherosclerotic cardiovascular disease patients, and in the statin intolerant subgroup NMA. Conclusions: All agents reduced LDL-C, however, the PCSK9 inhibitors evolocumab 140 mg Q2W / 420 mg QM and alirocumab 150 mg Q2W were the most effective LLT regimens for reducing LDL-C when added to statins.

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Recent lipid-lowering trials in perspective: implications for therapy

Hyperlipidaemia ◽

10.1093/med/9780199543502.003.0010 ◽

2011 ◽

pp. 111-119

Keyword(s):

Meta Analysis ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Controlled Trials ◽

Low Density ◽

Coronary Syndrome ◽

Clinical Benefits ◽

Prevention Trials ◽

Cvd Prevention

• Despite the clinical benefits of statin therapy in primary and secondary cardiovascular disease (CVD) prevention trials, considerable residual risk persists. • Meta-analysis of major randomized controlled trials (RCTs) suggests that greater low-density lipoprotein (LDL)-lowering is associated with greater reduction in events. • Recent RCTs in stable coronary disease and in acute coronary syndrome have demonstrated greater benefit with more intensive LDL-lowering. • The results of these trials have changed LDL goals of therapy for those at highest risk.

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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 ◽

10.1155/2021/9661752 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Tannaz Jamialahmadi ◽

Fatemeh Baratzadeh ◽

Željko Reiner ◽

Luis E. Simental-Mendía ◽

Suowen Xu ◽

...

Keyword(s):

Systematic Review ◽

Randomized Controlled Trials ◽

High Intensity ◽

Meta Analysis ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Moderate Intensity ◽

Controlled Trials ◽

Low Density ◽

Randomized Controlled

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 ; I 2 : 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 ; I 2 : 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 ; I 2 : 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.

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