Efficacy of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients with Heterozygous Familial Hypercholesterolemia: A Meta-analysis.

IF 2.8 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

American Journal of Cardiovascular Drugs Pub Date : 2024-09-20 DOI:10.1007/s40256-024-00682-0

Mahsa Movahedan, Ursula M Ellis, Arden R Barry

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引用次数: 0

Abstract

Background: Patients with heterozygous familial hypercholesterolemia (HeFH) are at high risk of major adverse cardiovascular events (MACE) and mortality. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), including monoclonal antibodies (alirocumab, evolocumab) and small interfering RNA (inclisiran), substantially reduce lipid levels. This meta-analysis aimed to evaluate the efficacy of both types of PCSK9i specifically in patients with HeFH.

Methods: A librarian-assisted systematic search of MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov was performed from 2013 to 2023. Randomized controlled trials of PCSK9i versus control in patients with HeFH were included. No language restrictions were applied. Cochrane Risk-of-Bias tool 2 was used to assess quality of evidence. Meta-analyses were performed using Cochrane ReviewManager. Outcomes included change in atherogenic lipids, MACE, and all-cause death.

Results: Seven trials were included (N = 2196). Overall risk of bias was mostly low or with some concerns. Median follow-up was 24 weeks. PCSK9i had an uncertain effect on MACE (odds ratio [OR] 1.25, 95% confidence interval [CI] 0.69-2.26) and all-cause death (OR 2.47, 95% CI 0.33-18.26) due to the low event rate and short follow-up. However, PCSK9i significantly reduced low-density lipoprotein cholesterol (LDL-C) by 54% (95% CI 49-58), apolipoprotein B by 43% (95% CI 37-49), and lipoprotein(a) by 20% (95% CI 13-28).

Conclusions: In patients with HeFH, PCSK9i significantly reduced atherogenic lipids (LDL-C, apolipoprotein B, and lipoprotein[a]). Despite this, the effect on MACE or all-cause death was unclear. Larger-scale randomized controlled trials of longer duration are needed to validate whether this short-term reduction in lipid levels translates into a reduction in clinically meaningful outcomes.

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Proprotein Convertase Subtilisin/Kexin Type 9 抑制剂对杂合家族性高胆固醇血症患者的疗效：一项 Meta 分析。

背景：杂合子家族性高胆固醇血症（HeFH）患者发生主要不良心血管事件（MACE）和死亡的风险很高。Proprotein convertase subtilisin/kexin type 9 抑制剂（PCSK9i），包括单克隆抗体（alirocumab、evolocumab）和小干扰 RNA（inclisiran），可显著降低血脂水平。这项荟萃分析旨在评估这两种 PCSK9i 对 HeFH 患者的疗效：在图书管理员的协助下，对2013年至2023年期间的MEDLINE、Embase、CENTRAL和ClinicalTrials.gov进行了系统检索。研究纳入了针对 HeFH 患者的 PCSK9i 与对照组的随机对照试验。无语言限制。采用 Cochrane Risk-of-Bias 工具 2 评估证据质量。使用 Cochrane ReviewManager 进行元分析。结果包括致动脉粥样硬化血脂的变化、MACE和全因死亡：结果：共纳入七项试验（N = 2196）。总体偏倚风险大多较低或存在一些问题。中位随访时间为 24 周。由于事件发生率低和随访时间短，PCSK9i对MACE（几率比[OR] 1.25，95% 置信区间[CI] 0.69-2.26）和全因死亡（OR 2.47，95% 置信区间[CI] 0.33-18.26）的影响不确定。然而，PCSK9i能显著降低低密度脂蛋白胆固醇（LDL-C）54%（95% CI 49-58）、载脂蛋白B 43%（95% CI 37-49）和脂蛋白（a）20%（95% CI 13-28）：结论：PCSK9i能显著降低HeFH患者的致动脉粥样硬化血脂（低密度脂蛋白胆固醇、载脂蛋白B和脂蛋白[a]）。尽管如此，对MACE或全因死亡的影响尚不明确。需要进行更大规模、持续时间更长的随机对照试验，以验证这种短期血脂水平的降低是否会转化为有临床意义的结果的减少。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American Journal of Cardiovascular Drugs 医学-心血管系统

CiteScore

6.70

自引率

3.30%

发文量

审稿时长

>12 weeks

期刊介绍： Promoting rational therapy within the discipline of cardiology, the American Journal of Cardiovascular Drugs covers all aspects of the treatment of cardiovascular disorders, particularly the place in therapy of newer and established agents. Via a program of reviews and original clinical research articles, the journal addresses major issues relating to treatment of these disorders, including the pharmacology, efficacy and adverse effects of the major classes of drugs; information on newly developed drugs and drug classes; the therapeutic implications of latest research into the aetiology of cardiovascular disorders; and the practical management of specific clinical situations. The American Journal of Cardiovascular Drugs offers a range of additional enhanced features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by a Key Points summary, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist patients, caregivers and others in understanding important medical advances. The journal also provides the option to include various other types of enhanced features including slide sets, videos and animations. All enhanced features are peer reviewed to the same high standard as the article itself. Peer review is conducted using Editorial Manager®, supported by a database of international experts. This database is shared with other Adis journals.