他汀类药物、依折麦布和他汀类药物-依折麦布疗法对杂合性家族性高胆固醇血症儿童和青少年的疗效和安全性：随机对照试验的系统综述、配对分析和网络荟萃分析。

IF 4.9 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Atherosclerosis Pub Date : 2024-09-28 DOI:10.1016/j.atherosclerosis.2024.118598

Alexis Llewellyn, Mark Simmonds, David Marshall, Melissa Harden, Beth Woods, Steve E Humphries, Uma Ramaswami, Lorraine Priestley-Barnham, Mark Fisher, Laila J Tata, Nadeem Qureshi

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引用次数: 0

摘要

背景和目的：他汀类药物、依折麦布和他汀类药物-依折麦布联合疗法是杂合子家族性高胆固醇血症（HeFH）患儿的推荐降脂疗法（LLTs）。然而，人们对它们的相对有效性还不甚了解。我们旨在通过直接和间接比较来比较这些疗法的安全性和有效性：我们对他汀类药物、依折麦布和他汀类药物-依折麦布联合疗法的随机对照试验（RCT）进行了系统回顾、配对分析和网络荟萃分析（NMAs）：共纳入 13 项随机对照试验（n = 1649，中位年龄 13 岁，随访 6 周-2 年）。所有低密度脂蛋白胆固醇疗法都能降低低密度脂蛋白胆固醇（LDL-C）和总胆固醇；他汀类药物能增加高密度脂蛋白胆固醇并降低甘油三酯。与安慰剂相比，他汀类药物可使低密度脂蛋白胆固醇降低 33.61%（95 % CI 27.58 至 39.63，I2 = 83 %）。在他汀类药物基础上添加依折麦布可使低密度脂蛋白胆固醇再降低 15.85 %（95 % CI 11.91 至 19.79）。NMA显示，与低剂量他汀类药物相比，中等剂量他汀类药物可额外降低4.77%的LDL-C（95 % CrI -11.22至1.05）；高剂量他汀类药物和中等剂量他汀类药物+依折麦布可能具有类似的效果，并且可能优于依折麦布、中等剂量和低剂量他汀类药物。没有证据表明LLTs与安慰剂在成熟度、安全性或耐受性方面存在差异：他汀类药物、依折麦布和他汀类药物-依折麦布都是治疗 HeFH 儿童的有效药物，但低密度脂蛋白胆固醇的降低幅度各不相同，可能取决于治疗剂量和组合。未发现安全性或耐受性问题。长期安全性和有效性尚不确定。

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Efficacy and safety of statins, ezetimibe and statins-ezetimibe therapies for children and adolescents with heterozygous familial hypercholesterolaemia: Systematic review, pairwise and network meta-analyses of randomised controlled trials.

Background and aims: Statins, ezetimibe and statins-ezetimibe combination therapy are recommended lipid-lowering therapies (LLTs) in children with heterozygous familial hypercholesterolaemia (HeFH). However, their relative effectiveness is not well understood. We aimed to compare the safety and efficacy of these therapies using direct and indirect comparisons.

Methods: We conducted systematic review, pairwise and network meta-analyses (NMAs) of randomised-controlled trials (RCTs) of statins, ezetimibe and statins-ezetimibe combination therapy in people <18 years with HeFH. Comprehensive bibliographic searches were conducted in December 2022, and a Medline update in January 2024. NMA models accounted for drug class, statin type and dosage.

Results: Thirteen RCTs were included (n = 1649, median age 13 years, follow-up 6 weeks-2 years). All LLTs reduced low-density lipoprotein cholesterol (LDL-C) and total cholesterol; statins led to increases in high-density lipoprotein cholesterol and reductions in triglycerides. Statins reduced LDL-C by 33.61 % against placebo (95 % CI 27.58 to 39.63, I² = 83 %). Adding ezetimibe to statins reduced LDL-C by an additional 15.85 % (95 % CI 11.91 to 19.79). NMAs showed intermediate-dose statins reduced LDL-C by an additional 4.77 % compared with lower-doses statins (95 % CrI -11.22 to 1.05); higher-dose statins and intermediate-dose statins + ezetimibe may be similarly effective and are probably superior to ezetimibe, intermediate-and lower-dose statins. There was no evidence of differences in maturation, safety or tolerability between LLTs and placebo.

Conclusions: Statins, ezetimibe and statins-ezetimibe are all effective treatments for children with HeFH, but the magnitude of LDL-C reductions varies and may depend on treatment dosage and combination. No safety or tolerability issues were found. Longer-term safety and effectiveness are uncertain.

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来源期刊

Atherosclerosis 医学-外周血管病

CiteScore

9.80

自引率

3.80%

发文量

1269

审稿时长

36 days

期刊介绍： Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.