Pharmacologic and Genetic Downregulation of Proprotein Convertase Subtilisin/Kexin Type 9 and Survival From Sepsis.
endotoxins
lipid regulating agents
proprotein convertase subtilisin/kexin type 9
sepsis
septic shock
Journal
Critical care explorations
ISSN: 2639-8028
Titre abrégé: Crit Care Explor
Pays: United States
ID NLM: 101746347
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
medline:
13
11
2023
pubmed:
13
11
2023
entrez:
13
11
2023
Statut:
epublish
Résumé
Treatments that prevent sepsis complications are needed. Circulating lipid and protein assemblies-lipoproteins play critical roles in clearing pathogens from the bloodstream. We investigated whether early inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) may accelerate bloodstream clearance of immunogenic bacterial lipids and improve sepsis outcomes. Genetic and clinical epidemiology, and experimental models. Human genetics cohorts, secondary analysis of a phase 3 randomized clinical trial enrolling patients with cardiovascular disease (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402), and experimental murine models of sepsis. Nine human cohorts with sepsis (total Observational human cohort studies used genetic Across human cohort studies, the effect estimate for 28-day mortality after sepsis diagnosis associated with genetic PCSK9 inhibition may improve clinical outcomes in sepsis in preventive, pretreatment settings.
Identifiants
pubmed: 37954898
doi: 10.1097/CCE.0000000000000997
pmc: PMC10635596
doi:
Banques de données
ClinicalTrials.gov
['NCT01663402']
Types de publication
Journal Article
Langues
eng
Pagination
e0997Informations de copyright
Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.
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