Contact information
Type
Scientific
Primary contact
Prof FGR Fowkes
ORCID ID
Contact details
Wolfson Unit for Prevention of Peripheral Vascular Diseases
University of Edinburgh
Teviot Place
Edinburgh
EH8 9AG
United Kingdom
+44 (0)131 650 3219
Gerry.Fowkes@ed.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
RG/97006; 057762
Study information
Scientific title
Randomised controlled trial of low dose Aspirin in the prevention of cardiovascular events and death in subjects with Asymptomatic Atherosclerosis
Acronym
AAA Trial
Study hypothesis
Primary prevention strategies aimed at modifying cardiovascular risk factors in otherwise healthy individuals have proved of only limited benefit in the primary prevention of cardiovascular disease. It is possible to identify in the general population large numbers of subjects with asymptomatic preclinical atherosclerosis who are at high risk of subsequent cardiovascular events using a simple blood pressure measurement - the Ankle Brachial Pressure Index (ABPI). We are currently conducting the first prevention trial on such high-risk subjects to determine whether low dose aspirin can reduce the incidence of cardiovascular events and death. 3,350 subjects aged over 50 years with an ABPI of at least 0.95 but no history of cardiovascular disease have been randomised into this double-blind placebo-controlled trial.
The principal hypothesis is that treatment of subjects with asymptomatic atherosclerosis, using low-dose aspirin, prevents subsequent cardiovascular disease indicated by incidence of major cardiovascular and cerebrovascular events.
An additional endpoint was added to this trial shortly after funding was obtained for the original AAA trial. As this additional endpoint has little to do with cardiovascular disease, funding was sought, and gained, from the Wellcome Trust. This end point was known as the Randomised controlled trial of aspirin in the reduction of age associated cognitive decline, and any information relating only to this endpoint will be headed with the title: Cognitive decline endpoint
The aim of this endpoint is to determine whether low dose aspirin treatment over a five-year period reduces cognitive decline in subjects at high risk of cardiovascular disease.
Ethics approval
AAA Trial:
1. Lanarkshire Research Ethics Committee: date of approval 22/04/1997 (ref: ER/4/97/8)
2. Greater Glasgow Community/Primary Care Local Research Ethics Committee: date of approval 14/06/1999 (ref: 45A/99)
3. Lothian Research Ethics Committee: date of approval 31/05/1999 (ref: 1702/99/3/23)
Cognitive Study:
1. Lanarkshire Research Ethics Committee: date of approval 26/10/1999 (ref: ER/49/10/99)
2. Greater Glasgow Community/Primary Care Local Research Ethics Committee: details as for AAA Trial (see above)
3. Lothian Research Ethics Committee: amendment to AAA Trial made and approved on 11/10/1999
Study design
Randomised, placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Cardiovascular disease, cognitive decline
Intervention
100 mg enteric-coated aspirin daily for five years or placebo daily for five years
The trials were initially designed to end simultaneously, but follow-up in the AAA Trial has been extended (with corresponding supplementary funding from BHF and CSO) to obtain the required number of major cardiovascular endpoints. Similar power considerations were not necessary for the cognitive decline endpoint; therefore the end date for the cognitive decline endpoint is 31st April 2006.
Public contact for the cognitive decline endpoint:
Dr Jackie Price
Community Health Sciences
University of Edinburgh Medical School
Teviot Place
Edinburgh
EH8 9AG
United Kingdom
Tel: +44 (0)131 650 3240
Fax: +44 (0)131 650 6904
Email: Jackie.Price@ed.ac.uk
Intervention type
Drug
Phase
Not Applicable
Drug names
Aspirin
Primary outcome measures
Myocardial infarction and stroke (fatal and non-fatal) or revascularisation
Cognitive decline endpoint:
A detailed battery of tests was administered to assess a broad range of the participants cognitive functions. The test battery was administered in a quiet room either in the clinic or at the patients home by a trained researcher. The order of tests in the battery was predetermined. The Mini Mental State Examination (MMSE) was included as a general mental assessment and as a screen for dementia. Executive function was assessed with use of the Verbal Fluency Test, which requires participants to generate as many words as possible with a specified initial letter (C, F and L).
As a measure of non-verbal reasoning, participants were asked to work through all five sets (A to E) of the Ravens Progressive Matrices, and were scored according to the number of items they completed correctly within 20 minutes. Immediate and delayed memory was assessed using a participants total score on the first five trials (I through V) of the Auditory Verbal Learning Test.
As a measure of mental flexibility, the Trail Making Test was administered and the time taken to complete part B was used in the subsequent analysis. In the Digit Symbol Test, used as a measure of speed of information processing, the number of symbols matched correctly to their corresponding numbers in 90 seconds was recorded.
The Hospital Anxiety and Depression Scale (HAD A and HAD D) was also used for the assessment of mood states, as these can affect performance on the tests, and the National Adult Reading Test (NART) was used to estimate Intelligence Quotient (IQ).
Secondary outcome measures
1. Total cardiovascular mortality
2. All cause mortality
3. Angina
4. Intermittent claudication
5. Transient ischaemic attack
6. Side effects/adverse events
Overall trial start date
01/04/1998
Overall trial end date
31/12/2009
Reason abandoned
Eligibility
Participant inclusion criteria
1. Men and women aged between 50 and 80 years
2. Ankle brachial pressure index 0.95 or less in at least one limb
3. Living in central Scotland (Lothian, Greater Glasgow and Lanarkshire)
4. No history of clinical cardiovascular disease
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
3350 (recruitment ended as of 1st February 2002)
Participant exclusion criteria
1. Receiving aspirin and/or other anticoagulants
2. Contraindication to aspirin therapy
Recruitment start date
01/04/1998
Recruitment end date
31/12/2009
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Wolfson Unit for Prevention of Peripheral Vascular Diseases
Edinburgh
EH8 9AG
United Kingdom
Sponsor information
Organisation
University of Edinburgh (UK)
Sponsor details
ACCORD Office
The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
British Heart Foundation (UK) (ref: RG/97006)
Alternative name(s)
BHF
Funding Body Type
private sector organisation
Funding Body Subtype
foundation
Location
United Kingdom
Funder name
Chief Scientist Office (CSO) (UK) (ref: K/OPR/2/2/D320)
Alternative name(s)
CSO
Funding Body Type
government organisation
Funding Body Subtype
government non-federal
Location
United Kingdom
Funder name
Cognitive decline endpoint:
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The Wellcome Trust (UK) (grant ref: 057762)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
1. 2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18762476
2. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20197530
3. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21223551
Publication citations
-
Results
Price JF, Stewart MC, Deary IJ, Murray GD, Sandercock P, Butcher I, Fowkes FG, , Low dose aspirin and cognitive function in middle aged to elderly adults: randomised controlled trial., BMJ, 2008, 337, a1198.
-
Results
Fowkes FG, Price JF, Stewart MC, Butcher I, Leng GC, Pell AC, Sandercock PA, Fox KA, Lowe GD, Murray GD, , Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial., JAMA, 2010, 303, 9, 841-848, doi: 10.1001/jama.2010.221.
-
Results
Eborall HC, Stewart MC, Cunningham-Burley S, Price JF, Fowkes FG, Accrual and drop out in a primary prevention randomised controlled trial: qualitative study., Trials, 2011, 12, 7, doi: 10.1186/1745-6215-12-7.