Rationale and design of a randomized controlled trial of pneumococcal polysaccharide vaccine for prevention of cardiovascular events: The Australian Study for the Prevention through Immunization of Cardiovascular Events (AUSPICE).
BACKGROUND
Research has shown that vaccination with Streptococcus pneumoniae reduced the extent of atherosclerosis in experimental animal models. It is thought that phosphorylcholine lipid antigens in the S. pneumoniae cell wall induce the production of antibodies that cross-react with oxidized low-density lipoprotein, a component of atherosclerotic plaques. These antibodies may bind to and facilitate the regression of the plaques. Available data provide evidence that similar mechanisms also occur in humans, leading to the possibility that pneumococcal vaccination protects against atherosclerosis. A systematic review and meta-analysis, including 8 observational human studies, of adult pneumococcal polysaccharide vaccination for preventing cardiovascular disease in people older than 65 years, showed a 17% reduction in the odds (odds ratio 0.83, 95% CI 0.71-0.97) of having an acute coronary syndrome event.


METHODS
The AUSPICE is a multicenter, randomized, placebo-controlled, double-blind, clinical trial to formally test whether vaccination with the pneumococcal polysaccharide vaccine protects against cardiovascular events (fatal and nonfatal acute coronary syndromes and ischemic strokes). Cardiovascular outcomes will be obtained during 4 to 5 years of follow-up, through health record linkage with state and national administrative data sets.


CONCLUSIONS
This is the first registered randomized controlled trial (on US, World Health Organization, Australia and New Zealand trial registries) to be conducted to test whether vaccination with the pneumococcal polysaccharide vaccine will reduce cardiovascular events. If successful, vaccination can be readily extended to at-risk groups to reduce the risk of cardiovascular diseases.
School of Medicine and Public Health, University of Newcastle, NSW, Australia. Electronic address: shu.ren@uon.edu.au.
Shu
S
Ren
School of Medicine and Public Health, University of Newcastle, NSW, Australia. Electronic address: alexis.hure@newcastle.edu.au.
Alexis
A
Hure
School of Medicine and Public Health, University of Newcastle, NSW, Australia. Electronic address: Roseanne.peel@newcastle.edu.au.
Roseanne
R
Peel
National Centre for Epidemiology and Population Health (NCEPH), Research School of Population Health, Australian National University, ACT, Australia. Electronic address: catherine.deste@anu.edu.au.
Catherine
C
D'Este
Canberra Hospital, Australian National University Medical School, ACT, Australia. Electronic address: walter.abhayaratna@act.gov.au.
Walter
W
Abhayaratna
Department of Epidemiology and Preventive Medicine, Monash University, VIC, Australia. Electronic address: andrew.tonkin@monash.edu.
Andrew
A
Tonkin
Department of Epidemiology and Preventive Medicine, Monash University, VIC, Australia. Electronic address: ingrid.hopper@monash.edu.
Ingrid
I
Hopper
Stroke and Ageing Research, Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, VIC, Australia. Electronic address: amanda.thrift@monash.edu.
Amanda G
AG
Thrift
School of Medicine and Public Health, University of Newcastle, NSW, Australia. Electronic address: christopher.levi@hnehealth.nsw.gov.au.
Christopher
C
Levi
School of Medicine and Public Health, University of Newcastle, NSW, Australia. Electronic address: jonathan.sturm@newcastle.edu.au.
Jonathan
J
Sturm
Hunter New England Population Health, Hunter Medical Research Institute, NSW, Australia. Electronic address: david.durrheim@hnehealth.nsw.gov.au.
David
D
Durrheim
School of Medicine and Pharmacology, University of Western Australia, WA, Australia. Electronic address: joe.hung@uwa.edu.au.
Joseph
J
Hung
School of Population Health, University of Western Australia, WA, Australia. Electronic address: tom.briffa@uwa.edu.au.
Thomas
T
Briffa
School of Medicine, Flinders University, SA, Australia. Electronic address: derek.chew@flinders.edu.au.
Derek P
DP
Chew
Australian Institute of Health and Welfare, ACT, Australia. Electronic address: phil.anderson@aihw.gov.au.
Phil
P
Anderson
Australian Institute of Health and Welfare, ACT, Australia. Electronic address: lynelle.moon@aihw.gov.au.
Lynelle
L
Moon
School of Medicine and Public Health, University of Newcastle, NSW, Australia. Electronic address: mark.mcevoy@newcastle.edu.au.
Mark
M
McEvoy
School of Biomedical Sciences and Pharmacy, University of Newcastle, NSW, Australia. Electronic address: philip.hansbro@newcastle.edu.au.
Philip
P
Hansbro
School of Medicine and Public Health, University of Newcastle, NSW, Australia. Electronic address: david.newby@newcastle.edu.au.
David
D
Newby
School of Medicine and Public Health, University of Newcastle, NSW, Australia. Electronic address: john.attia@newcastle.edu.au.
John
J
Attia
D054058:Acute Coronary Syndrome / Q000276:immunology / Q000517:prevention & control*; D000907:Antibodies, Bacterial / Q000276:immunology; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000276:immunology / Q000517:prevention & control*; D001315:Australia; D002318:Cardiovascular Diseases / Q000276:immunology / Q000517:prevention & control; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000276:immunology / Q000517:prevention & control; D059168:Carotid Intima-Media Thickness; D003429:Cross Reactions / Q000276:immunology; D004311:Double-Blind Method; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology; D008875:Middle Aged; D016017:Odds Ratio; D022242:Pneumococcal Vaccines / Q000627:therapeutic use*; D063177:Pulse Wave Analysis; D020521:Stroke / Q000276:immunology / Q000517:prevention & control*
D000907:Antibodies, Bacterial; D008077:Lipoproteins, LDL; D022242:Pneumococcal Vaccines; C099252:oxidized low density lipoprotein