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open access

Vol 74, No 3 (2023)
Review paper
Submitted: 2022-10-07
Accepted: 2023-04-02
Published online: 2023-06-12
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Impact of alirocumab/evolocumab on lipoprotein (a) concentrations in patients with familial hypercholesterolaemia: a systematic review and meta-analysis of randomized controlled trials

Haibing Dai12, Yonglin Zhu12, Zuyi Chen12, Renqing Yan12, Jinsong Liu12, Ziyun He12, Lin Zhang3, Feng Zhang12, Shengkai Yan1
DOI: 10.5603/EP.a2023.0036
·
Pubmed: 37335067
·
Endokrynol Pol 2023;74(3):234-242.
Affiliations
  1. Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China
  2. College of Laboratory Medicine, Zunyi Medical University, Zunyi, China
  3. School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

open access

Vol 74, No 3 (2023)
Review Article
Submitted: 2022-10-07
Accepted: 2023-04-02
Published online: 2023-06-12

Abstract

Introduction: Familial hypercholesterolaemia (FH) is a common hereditary genetic disorder, characterized by elevated circulating low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] concentrations, leading to atherosclerotic cardiovascular disease (ASCVD). Two types of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors — alirocumab and evolocumab — are efficient drugs in the treatment of FH, which can effectively reduce Lp(a) levels.

Material and methods: Embase, MEDLINE, and PubMed up to November 2022 were searched for randomized clinical trials (RCTs) evaluating the effect of alirocumab/evolocumab and placebo treatment on plasma Lp(a) levels in FH. Statistics were analysed by Review Manager (RevMan 5.3) and Stata 15.1.

Results: Eleven RCTs involved a total of 2408 participants. Alirocumab/evolocumab showed a significant efficacy in reducing Lp(a) [weighted mean difference (WMD): –20.10%, 95% confidence interval (CI): –25.59% to –14.61%] compared with placebo. In the drug type subgroup analyses, although the efficacy of evolocumab was slightly low (WMD: –19.98%, 95% CI: –25.23% to –14.73%), there was no difference with alirocumab (WMD: –20.54%, 95% CI: –30.07% to –11.02%). In the treatment duration subgroup analyses, the efficacy of the 12-week duration group (WMD: –17.61%, 95% CI: –23.84% to –11.38%) was lower than in the group of ≥ 24 weeks’ duration (WMD: –22.81%, 95% CI: –31.56% to –14.07%). In the participants’ characteristics subgroup analyses, the results showed that no differential effect of alirocumab/evolocumab therapy on plasma Lp(a) concentrations was observed (heterozygous FH [HeFH] WMD: –20.07%, 95% CI: –26.07% to –14.08%; homozygous FH [HoFH] WMD: –20.04%, 95% CI: –36.31% to –3.77%). Evaluation of all-cause adverse events (AEs) between alirocumab/evolocumab groups and placebo groups [relative risk (RR): 1.05, 95% CI: 0.98–1.12] implied no obvious difference between the 2 groups.

Conclusions: Anti-PCSK9 drugs (alirocumab and evolocumab) may be effective as therapy for reducing serum Lp(a) levels in FH, and no differences were observed in treatment durations, participant characteristics, and other aspects of the 2 types of PCSk9 inhibitors.

However, further experimental studies and RCTs are warranted to clarify the mechanism of PSCK9 inhibitors to lowering Lp(a) concentrations in FH.

Abstract

Introduction: Familial hypercholesterolaemia (FH) is a common hereditary genetic disorder, characterized by elevated circulating low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] concentrations, leading to atherosclerotic cardiovascular disease (ASCVD). Two types of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors — alirocumab and evolocumab — are efficient drugs in the treatment of FH, which can effectively reduce Lp(a) levels.

Material and methods: Embase, MEDLINE, and PubMed up to November 2022 were searched for randomized clinical trials (RCTs) evaluating the effect of alirocumab/evolocumab and placebo treatment on plasma Lp(a) levels in FH. Statistics were analysed by Review Manager (RevMan 5.3) and Stata 15.1.

Results: Eleven RCTs involved a total of 2408 participants. Alirocumab/evolocumab showed a significant efficacy in reducing Lp(a) [weighted mean difference (WMD): –20.10%, 95% confidence interval (CI): –25.59% to –14.61%] compared with placebo. In the drug type subgroup analyses, although the efficacy of evolocumab was slightly low (WMD: –19.98%, 95% CI: –25.23% to –14.73%), there was no difference with alirocumab (WMD: –20.54%, 95% CI: –30.07% to –11.02%). In the treatment duration subgroup analyses, the efficacy of the 12-week duration group (WMD: –17.61%, 95% CI: –23.84% to –11.38%) was lower than in the group of ≥ 24 weeks’ duration (WMD: –22.81%, 95% CI: –31.56% to –14.07%). In the participants’ characteristics subgroup analyses, the results showed that no differential effect of alirocumab/evolocumab therapy on plasma Lp(a) concentrations was observed (heterozygous FH [HeFH] WMD: –20.07%, 95% CI: –26.07% to –14.08%; homozygous FH [HoFH] WMD: –20.04%, 95% CI: –36.31% to –3.77%). Evaluation of all-cause adverse events (AEs) between alirocumab/evolocumab groups and placebo groups [relative risk (RR): 1.05, 95% CI: 0.98–1.12] implied no obvious difference between the 2 groups.

Conclusions: Anti-PCSK9 drugs (alirocumab and evolocumab) may be effective as therapy for reducing serum Lp(a) levels in FH, and no differences were observed in treatment durations, participant characteristics, and other aspects of the 2 types of PCSk9 inhibitors.

However, further experimental studies and RCTs are warranted to clarify the mechanism of PSCK9 inhibitors to lowering Lp(a) concentrations in FH.

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Keywords

familial hypercholesterolaemia; lipoprotein (a); atherosclerotic cardiovascular disease; PCSK9 inhibitors; meta-analysis; randomized controlled trials

About this article
Title

Impact of alirocumab/evolocumab on lipoprotein (a) concentrations in patients with familial hypercholesterolaemia: a systematic review and meta-analysis of randomized controlled trials

Journal

Endokrynologia Polska

Issue

Vol 74, No 3 (2023)

Article type

Review paper

Pages

234-242

Published online

2023-06-12

Page views

2024

Article views/downloads

1039

DOI

10.5603/EP.a2023.0036

Pubmed

37335067

Bibliographic record

Endokrynol Pol 2023;74(3):234-242.

Keywords

familial hypercholesterolaemia
lipoprotein (a)
atherosclerotic cardiovascular disease
PCSK9 inhibitors
meta-analysis
randomized controlled trials

Authors

Haibing Dai
Yonglin Zhu
Zuyi Chen
Renqing Yan
Jinsong Liu
Ziyun He
Lin Zhang
Feng Zhang
Shengkai Yan

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