Effect of aspirin on deaths associated with sepsis in healthy older people (ANTISEPSIS): a randomised, double-blind, placebo-controlled primary prevention trial.
Journal
The Lancet. Respiratory medicine
ISSN: 2213-2619
Titre abrégé: Lancet Respir Med
Pays: England
ID NLM: 101605555
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
07
05
2020
revised:
06
08
2020
accepted:
21
08
2020
pubmed:
21
9
2020
medline:
20
2
2021
entrez:
20
9
2020
Statut:
ppublish
Résumé
Sepsis is a serious global health issue and a major cause of death and disability. The availability of a simple, community-based preventive strategy could substantially reduce the burden of sepsis. We aimed to establish whether low-dose aspirin reduced deaths or hospital admissions associated with sepsis in older people. ANTISEPSIS was a substudy of ASPREE (a randomised controlled primary prevention trial of low-dose aspirin [100 mg per day] compared with placebo in community dwelling older adults conducted in Australia and the USA), with the Australian cohort included in the ANTISEPSIS substudy. Inclusion criteria were participants aged at least 70 years who did not have major illnesses. Participants were block randomised (1:1) via a centralised web portal and stratified by general practice and age. Participants, investigators, and staff were masked to the intervention. Teams of clinical specialist investigators assessed potential sepsis events to establish if they satisfied the primary endpoint of death associated with sepsis. The analyses were by intention-to-treat with univariate survival analysis methods, the log-rank test, and Cox proportional hazards regression. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000349741. Between March 10, 2010, and Dec 24, 2014, of 20 288 individuals assessed for eligibility, 16 703 participants aged 70 years and older at trial entry were enrolled and followed up for a median of 4·6 years (IQR 3·6-5·6). 8322 (49·8%) participants were assigned to receive aspirin and 8381 (50·2%) to placebo. 203 deaths were considered to be associated with sepsis. Univariate analysis showed similar rates of death associated with sepsis in the two study groups (hazard ratio for aspirin vs placebo 1·08, 95% CI 0·82-1·43; p=0·57). Adverse events were previously reported in the ASPREE trial. Daily low-dose aspirin treatment did not reduce deaths associated with sepsis in community dwelling older adults. Our findings do not support the use of aspirin as a primary prevention strategy to reduce the burden of sepsis in this population. National Health and Medical Research Council of Australia, National Institutes of Health, Monash University.
Sections du résumé
BACKGROUND
Sepsis is a serious global health issue and a major cause of death and disability. The availability of a simple, community-based preventive strategy could substantially reduce the burden of sepsis. We aimed to establish whether low-dose aspirin reduced deaths or hospital admissions associated with sepsis in older people.
METHODS
ANTISEPSIS was a substudy of ASPREE (a randomised controlled primary prevention trial of low-dose aspirin [100 mg per day] compared with placebo in community dwelling older adults conducted in Australia and the USA), with the Australian cohort included in the ANTISEPSIS substudy. Inclusion criteria were participants aged at least 70 years who did not have major illnesses. Participants were block randomised (1:1) via a centralised web portal and stratified by general practice and age. Participants, investigators, and staff were masked to the intervention. Teams of clinical specialist investigators assessed potential sepsis events to establish if they satisfied the primary endpoint of death associated with sepsis. The analyses were by intention-to-treat with univariate survival analysis methods, the log-rank test, and Cox proportional hazards regression. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000349741.
RESULTS
Between March 10, 2010, and Dec 24, 2014, of 20 288 individuals assessed for eligibility, 16 703 participants aged 70 years and older at trial entry were enrolled and followed up for a median of 4·6 years (IQR 3·6-5·6). 8322 (49·8%) participants were assigned to receive aspirin and 8381 (50·2%) to placebo. 203 deaths were considered to be associated with sepsis. Univariate analysis showed similar rates of death associated with sepsis in the two study groups (hazard ratio for aspirin vs placebo 1·08, 95% CI 0·82-1·43; p=0·57). Adverse events were previously reported in the ASPREE trial.
INTERPRETATION
Daily low-dose aspirin treatment did not reduce deaths associated with sepsis in community dwelling older adults. Our findings do not support the use of aspirin as a primary prevention strategy to reduce the burden of sepsis in this population.
FUNDING
National Health and Medical Research Council of Australia, National Institutes of Health, Monash University.
Identifiants
pubmed: 32950072
pii: S2213-2600(20)30411-2
doi: 10.1016/S2213-2600(20)30411-2
pmc: PMC7957956
mid: NIHMS1677399
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Aspirin
R16CO5Y76E
Banques de données
ANZCTR
['ACTRN12613000349741']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
186-195Subventions
Organisme : NIA NIH HHS
ID : P30 AG024824
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG029824
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG062682
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
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