Tackling heart disease: the Scottish aspirin trial

ISRCTN	ISRCTN66587262
DOI	https://doi.org/10.1186/ISRCTN66587262
Secondary identifying numbers	RG/97006; 057762

Submission date: 31/01/2002
Registration date: 31/01/2002
Last edited: 17/02/2015

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof FGR Fowkes
Scientific

Wolfson Unit for Prevention of Peripheral Vascular Diseases
University of Edinburgh
Teviot Place
Edinburgh
EH8 9AG
United Kingdom

Phone	+44 (0)131 650 3219
Email	Gerry.Fowkes@ed.ac.uk

Dr Jackie Price
Public

Community Health Sciences
University of Edinburgh Medical School
Teviot Place
Edinburgh
EH8 9AG
United Kingdom

Phone	+44 (0)131 650 3240
Email	Jackie.Price@ed.ac.uk

Study information

Study design	Randomised placebo-controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Other
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Randomised controlled trial of low dose Aspirin in the prevention of cardiovascular events and death in subjects with Asymptomatic Atherosclerosis
Study acronym	AAA Trial
Study objectives	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(s)	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
Health condition(s) or problem(s) studied	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 31/04/2006.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Aspirin
Primary outcome measure	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 patient's 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 Raven's 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 participant's 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 study start date	01/04/1998
Completion date	31/12/2009

Eligibility

Participant type(s)	Patient
Age group	Senior
Sex	Both
Target number of participants	3350
Key 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
Key exclusion criteria	1. Receiving aspirin and/or other anticoagulants 2. Contraindication to aspirin therapy
Date of first enrolment	01/04/1998
Date of final enrolment	01/02/2002

Locations

Countries of recruitment

Scotland
United Kingdom

Study participating centre

Wolfson Unit for Prevention of Peripheral Vascular Diseases

Edinburgh
EH8 9AG
United Kingdom

Sponsor information

University of Edinburgh (UK)
University/education

ACCORD Office
The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
Scotland
United Kingdom

Website	http://www.ed.ac.uk/
"ROR"	https://ror.org/01nrxwf90

Funders

Funder type

Charity

British Heart Foundation (UK) (ref: RG/97006)
Private sector organisation / Trusts, charities, foundations (both public and private)

Alternative name(s): the_bhf, The British Heart Foundation, BHF
Location: United Kingdom

Chief Scientist Office (CSO) (UK) (ref: K/OPR/2/2/D320)
Government organisation / Local government

Alternative name(s): CSO
Location: United Kingdom

Wellcome Trust
Private sector organisation / International organizations

Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Peer reviewed?	Patient-facing?
Results article	results	01/09/2008	Yes	No
Results article	results	03/03/2010	Yes	No
Results article	results	11/01/2011	Yes	No