Damon P Eisen1, Karin Leder2, Robyn L Woods2, Jessica E Lockery2, Sarah L McGuinness3, Rory Wolfe2, David Pilcher4, Elizabeth M Moore2, Adithya Shastry2, Mark R Nelson5, Christopher M Reid6, John J McNeil2, Emma S McBryde7. 1. College of Medicine and Dentistry, James Cook University, Douglas, QLD, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. Electronic address: damon.eisen@jcu.edu.au. 2. School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. 3. School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Department of Infectious Diseases, Alfred Health, Prahran, VIC, Australia. 4. School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Department of Intensive Care, Alfred Health, Prahran, VIC, Australia. 5. Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia. 6. School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; The School of Public Health, Curtin University, Bentley, WA, Australia. 7. Australian Institute of Tropical Health and Medicine, James Cook University, Douglas, QLD, Australia.
Abstract
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.
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.
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