Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the risk for neurocognitive adverse events: A systematic review, meta-analysis and meta-regression.


Journal

International journal of cardiology
ISSN: 1874-1754
Titre abrégé: Int J Cardiol
Pays: Netherlands
ID NLM: 8200291

Informations de publication

Date de publication:
15 07 2021
Historique:
received: 26 01 2021
revised: 17 03 2021
accepted: 16 04 2021
pubmed: 24 4 2021
medline: 8 7 2021
entrez: 23 4 2021
Statut: ppublish

Résumé

It has been suggested that lipid lowering therapy causes impaired cognitive changes. The association between the use of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the risk of neurocognitive adverse events remains unclear. This meta-analysis aims to assess neurocognitive safety of PCSK9 inhibitors in randomized controlled trials (RCTs). The research was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed (MEDLINE), Embase and Cochrane library were searched through September 2019. Selection criteria included RCTs that addressed to neurocognitive adverse events of participants using Alirocumab, Evolocumab or Bococizumab, with a follow up duration of at least 6 months. The search results were screened by two independent reviewers. Safety data from included papers were extracted. Random effects meta-analysis was used to pool results, and meta-regression was utilized when applicable. Twenty-one studies were included. Among 59,733 patients, 31,611 were treated with PCSK9 inhibitors. The follow-up period ranged from 24 weeks to 48 months. No significant difference in the incidence of neurocognitive adverse effects between the groups was identified (RR = 1.01, 95% CI: 0.86-1.19, I Pooled results of our meta-analysis and meta-regression show that exposure to PCSK9 inhibitors is not associated with an increased risk of neurocognitive adverse effects.

Sections du résumé

BACKGROUND
It has been suggested that lipid lowering therapy causes impaired cognitive changes. The association between the use of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the risk of neurocognitive adverse events remains unclear. This meta-analysis aims to assess neurocognitive safety of PCSK9 inhibitors in randomized controlled trials (RCTs).
METHODS AND RESULTS
The research was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed (MEDLINE), Embase and Cochrane library were searched through September 2019. Selection criteria included RCTs that addressed to neurocognitive adverse events of participants using Alirocumab, Evolocumab or Bococizumab, with a follow up duration of at least 6 months. The search results were screened by two independent reviewers. Safety data from included papers were extracted. Random effects meta-analysis was used to pool results, and meta-regression was utilized when applicable. Twenty-one studies were included. Among 59,733 patients, 31,611 were treated with PCSK9 inhibitors. The follow-up period ranged from 24 weeks to 48 months. No significant difference in the incidence of neurocognitive adverse effects between the groups was identified (RR = 1.01, 95% CI: 0.86-1.19, I
CONCLUSIONS
Pooled results of our meta-analysis and meta-regression show that exposure to PCSK9 inhibitors is not associated with an increased risk of neurocognitive adverse effects.

Identifiants

pubmed: 33892045
pii: S0167-5273(21)00661-6
doi: 10.1016/j.ijcard.2021.04.025
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
Anticholesteremic Agents 0
PCSK9 protein, human EC 3.4.21.-
Proprotein Convertase 9 EC 3.4.21.-
Subtilisins EC 3.4.21.-

Types de publication

Journal Article Meta-Analysis Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

7-14

Informations de copyright

Copyright © 2021 Elsevier B.V. All rights reserved.

Auteurs

Bruria Hirsh Raccah (B)

Division of Clinical Pharmacy, Institute for Drug Research, School of Pharmacy Faculty of Medicine, The Hebrew University of Jerusalem, Israel; Department of Cardiology, Hadassah University Hospital, Israel.

Alona Yanovsky (A)

Division of Clinical Pharmacy, Institute for Drug Research, School of Pharmacy Faculty of Medicine, The Hebrew University of Jerusalem, Israel.

Nir Treves (N)

Division of Clinical Pharmacy, Institute for Drug Research, School of Pharmacy Faculty of Medicine, The Hebrew University of Jerusalem, Israel.

Victoria Rotshild (V)

Division of Clinical Pharmacy, Institute for Drug Research, School of Pharmacy Faculty of Medicine, The Hebrew University of Jerusalem, Israel.

Christel Renoux (C)

Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Department of Epidemiology, Montreal, Québec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada.

Haim Danenberg (H)

Department of Cardiology, Hadassah University Hospital, Israel.

Ran Eliaz (R)

Department of Cardiology, Hadassah University Hospital, Israel.

Ilan Matok (I)

Division of Clinical Pharmacy, Institute for Drug Research, School of Pharmacy Faculty of Medicine, The Hebrew University of Jerusalem, Israel. Electronic address: Ilan.Matok@mail.huji.ac.il.

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Classifications MeSH