Comparative safety and efficacy of low- or moderate-intensity statin plus ezetimibe combination therapy and high-intensity statin monotherapy: A meta-analysis of randomized controlled studies.

Young-Mi Ah,Hye Duck Choi,Minseob Jeong,Tariq Jamal Siddiqi

doi:10.1371/journal.pone.0264437

Abstract

Statin is highly recommended for dyslipidemia to prevent atherosclerosis-related cardiovascular diseases and death. The aim of this study was to compare the efficacies and safeties of low/moderate-intensity statin plus ezetimibe combination therapy vs. high-intensity statin monotherapy. Meta-analysis was conducted on data included in published studies performed to compare the effects of the two treatments on lipid parameters and hs-CRP. Safety-related parameters were also evaluated. Eighteen articles were included in the meta-analysis. In terms of efficacy, low/moderate-intensity statin plus ezetimibe reduced LDL-C (SE = 0.307; 95% CI 0.153–0.463), TC (SE = 0.217; 95% CI 0.098–0.337), triglyceride (SE = 0.307; 95% CI 0.153–0.463), and hs-CRP (SE = 0.190; 95% CI 0.018–0.362) significantly more than high-intensity statin therapy. In terms of safety, the two treatments were not significantly different in terms of ALT elevation, but high-intensity statin increased AST and CK significantly more than combination therapy. This analysis indicates that low/moderate-intensity statin plus ezetimibe combined therapy is more effective and safer than high-intensity statin monotherapy, which suggests the addition of ezetimibe to statin should be preferred over increasing statin dose and that high-intensity statin should be used more carefully, especially in patients with related risks.

Highlights

Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) significantly reduce the risk of cardiovascular events and are considered first-line therapies for managing dyslipidemia or atherosclerosis cardiovascular diseases (ASCVDs) [1, 2]
Seventeen studies measured changes in low-density lipoprotein cholesterol (LDL-C) in 787 participants treated with high-intensity statin and 752 participants treated with low/moderate-intensity statin plus ezetimibe
Combination treatment afforded a significantly greater reduction in LDL-C than high-intensity statin treatment (SE = 0.307; 95% confidence interval (CI) 0.153–0.462) (Fig 2)

Summary

Introduction

Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) significantly reduce the risk of cardiovascular events and are considered first-line therapies for managing dyslipidemia or atherosclerosis cardiovascular diseases (ASCVDs) [1, 2]. Several statins are currently available and are selected based on individual ASCVD risk and indicated statin intensity [3]. High-intensity statins that lower low-density lipoprotein cholesterol (LDL-C) on average by 50% or more as daily dose are strongly recommended for patients at high risk, such as those with a history of at least one major ASCVD event Liver enzyme abnormalities are other notable adverse events during statin therapy [5]. Low dose statin therapy or a different treatment strategy should be considered for patients with risk factors for muscle or liver-related toxicities

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