Recruitment

Participants were recruited for ASPREE through two methods: general practice-based recruitment and community-based recruitment.

General Practitioner Recruitment

In Australia recruitment was carried out predominantly through general practices with general practitioners (GPs) registered as ASPREE co-investigators. GPs' clinical databases were searched by inclusion/exclusion criteria and a mailing list was created. After GP review, a final list of potential participants was used to generate invitation letters, sent by ASPREE on behalf of the GP. The letter directed the participant to respond to a toll free telephone number and, upon calling the number, interested participants were screened again and suitable persons invited to Visit 1 (week zero) at the GP’s clinic or a community venue. After an interim GP visit to discuss the study and check suitability again, participants returned at week four for Visit 2. Futher information about Australian recruitment has been published elsewhere.

In the US recruitment was community-based utilising a range of methods such as clinic-based, mailing lists, media advertisements, pre-existing registries and electronic medical records. Select sites in the US recruited Caucasians with a special focus on enriching the group with minority groups (African Americans, Hispanics, Native Americans and others). African American and Hispanic groups had a lower age criterion due to a higher burden of disease and a survival disadvantage. Minority recruitment was challenging due to a lower number of minorities without previous cardiovascular events, disability or dementia, who are not taking aspirin, and a reluctance to cease aspirin if not clinically indicated. In addition, after an NIH moratorium on recruiting US Caucasians was enacted in 2011, there was increased hesitancy expressed by minorities regarding why ASPREE was only recruiting minorities. This, at least in part, is why US recruitment numbers are lower compared to Australia.

Inclusion and Exclusion Criteria

Inclusion criteria:

  • Non-minority men and women 70 years of age and older;
  • US minority (African American and Hispanic) 65 years of age and older;
  • Willing and able to provide informed consent.

Exclusion criteria:

  • A history of a diagnosed CVD event defined as myocardial infarction (MI), heart failure, angina pectoris, stroke, transient ischemic attack, 50% carotid stenosis or previous carotid endarterectomy or stenting, coronary artery angioplasty or stenting, coronary artery bypass grafting, or abdominal aortic aneurysm;
  • A clinical diagnosis of atrial fibrillation;
  • Serious illness likely to cause death within the next five years;
  • A current or recurrent condition with a high risk of major bleeding;
  • Anaemia (haemoglobin < 12 g/dl males, < 11 g/dl females);
  • An absolute contraindication or allergy to aspirin;
  • Current participation in an ongoing clinical trial;
  • Current use of aspirin for secondary prevention;
  • Current continuous use of other antiplatelet drug or anticoagulant;
  • A systolic blood pressure ≥180 mmHg and/or a diastolic blood pressure ≥105 mmHg;
  • A history of dementia or a Modified Mini-Mental State Examination (3MS) score ≤77;
  • Severe difficulty or an inability to perform any one of the six Katz activities of daily living (ADLS);
  • Pill-taking compliance ≤80% during a four week placebo run-in phase.

People who were currently using aspirin for reasons other than secondary prevention entered the trial after agreeing to discontinue aspirin. Chronic use of non-steroidal anti-inflammatory drugs was not an exclusion criterion. During a four week run-in phase participants took placebo for compliance checking. Participants were initially instructed to take their study drug half an hour prior to any morning medication to minimise drug interactions. This instruction was subsequently rescinded.

Randomisation and Intervention

Participants were randomised remotely via AWARD-Data according to a computer-generated randomisation schedule, in a ratio of 1:1 to active or placebo therapy. Randomisation was stratified by general practice in Australia, by regional site in the USA and by age in both countries (65–69 years, 70–79 years, 80 years+). Randomisation was blocked within strata and utilised variable sized blocks of two, four, or six.

Participants in the study were allocated to one of two treatments ASA 100 mg enteric-coated unscored white tablet (Bayer Pharma AG (Germany)) or placebo enteric-coated unscored white tablet with identical appearance.

The study’s intervention phase concluded in June 2017. Study medication administration was ceased immediately and medication bottles were retrieved from all participants by mail or at in-person visits.

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