ASPIRIN TRIALS

Add-Aspirin (A phase III double-blind placebo-controlled randomised trial assessing the addition of aspirin after standard primary therapy in early stage common solid tumours (Sponsor – University College London (UK))
Start date – May 2014

Status – Currently ongoing, expected publication date 2026

Study population: Approximately 10,000 cancer survivors who have had (or are currently having) treatment for an early stage cancer of the breast, bowel, stomach, oesophagus or prostate in the UK and India

Study Design: RCT of 100mg aspirin, 300mg aspirin or a placebo (dummy) tablet for five years                                                     Aim: To assess whether regular aspirin use after standard therapy, including surgery and neo-adjuvant/adjuvant chemotherapy and/or radiotherapy, can prevent recurrence and prolong survival in participants with common solid tumours

ASPREE (ASPirin in Reducing Events in the Elderly) Monash University, Berman Center for Clinical Research & Outcomes                   Funded by National Institute on Aging (National Institutes of Health (US)), National Health and Medical Research Council of Australia (NHMRC), Victorian Cancer Agency (VCA, Australia)
Start date – March 2010 – Jan 2018
Status – Completed, publication of main papers 2018

Study Population: 16,703 Australians aged ≥ 70 years and 2,411 Americans aged ≥ 65 years for minority populations (55% of US recruitment) and ≥ 70 years for non-minority. Participants are able-bodied and have no history of CVD or a contraindication to take aspirin or placebo.

Study design: Primary prevention, double-blinded, placebo-controlled RCT of 100 mg daily enteric-coated aspirin or a matching placebo for an average of 5 years. Clinical health measures are undertaken annually.
The primary objective is to determine whether low-dose aspirin prolongs life, or life free of dementia, or life free of significant, persistent physical disability in the healthy elderly. Secondary objectives relate to the effects of low-dose aspirin on the key outcome areas of death, cardiovascular disease, dementia and cognitive decline, cancer, physical disability, depression and major bleeding episodes.

ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events)
International Multi-Centre RCT
Sponsor – Bayer
Start date – September 2007
Status – Completed. Findings published 2018

Study population: Approximately 12,000 participants at moderate cardiovascular disease (CVD) risk (Germany, Italy, Spain, UK, and USA).

Men aged ≥ 55 years with 2 – 4 CVD risk factors*
Women aged ≥ 60 years with 3 or more risk factors*
*Please note – CVD risk factors refers to: elevated total LDL cholesterol and/or low HDL cholesterol, cigarette smoking, elevated blood pressure, current use of medication to treat high blood pressure, and a family history of early coronary heart disease (CHD).

Study design: Primary prevention, double-blind randomised control trial (RCT) of low-dose aspirin (100mg) versus placebo for approximately 5 years.
Aim: The ARRIVE study is aiming to demonstrate the efficacy and safety of low-dose aspirin in preventing initial events associated with CVD in individuals with no known history of CVD, but who are at moderate risk.
The primary outcome of ARRIVE is a composite CVD/cerebrovascular endpoint, where time to first occurrence of either non-fatal heart attack, non-fatal ischaemic stroke or CVD death (including fatal heart attack, fatal ischaemic stroke).

ASCEND (A Study of Cardiovascular Events iN Diabetes)
(Sponsor – University of Oxford Clinical Trial Service Unit, UK Jane M Armitage, BSc, MBBS, MRCP, FFPH, Principal Investigator, Clinical Trial Service Unit, University of Oxford)
Start date – March 2005
Status – Completed. Findings published 2018

Study population: 15,400 individuals with diabetes (Type 1 or Type 2), no known vascular disease, aged >= 40 years
Males or females with type 1 or type 2 diabetes mellitus.
Aged ≥ 40 years.
No previous history of vascular disease.

Study design: Primary prevention, double-blind RCT, 2 x 2 factorial design of low-dose, enteric-coated aspirin (100mg) versus placebo, and of omega-3 fatty acid supplementation versus placebo, once daily for an average of 5 years
Aim: To determine whether or not low-dose aspirin and/or omega-3 fatty acid supplementation helps to reduce the development of circulatory problems (e.g. heart attack, stroke) in people with diabetes.

JPPP (Japanese Primary Prevention Project)

Keio University School of Medicine, Japan,
(Sponsors – Japan Heart Foundation & Bayer)
Start date – March 2005
Status – Prematurely terminated after a median follow-up of 5.02 years due to likely futility

Study population: 14,400 participants with asymptomatic atherosclerosis (ABI <= 0.95), no evidence of previous CV events, aged 60 – 85 years diagnosed with one or more of these conditions: hypertension, hyperlipidemia or diabetes

Study design: Primary prevention, open-label, randomised, parallel-group trial of low-dose, enteric-coated aspirin (100mg) versus control, once daily for an average of 8 years
Aim: To determine whether treatment of individuals with asymptomatic atherosclerosis using low-dose aspirin for 8 years prevents cardiovascular events (heart attack, stroke).

Conclusion: The study found once-daily, low-dose aspirin did not significantly reduce the risk of the composite outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction among Japanese patients 60 years or older with atherosclerotic risk factors. (Ikeda Y, Shimada K, Teramoto T et al. Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Japanese Patients 60 Years or Older With Atherosclerotic Risk Factors: A Randomized Clinical Trial. JAMA. 2014;312(23):2510-2520. doi:10.1001/jama.2014.15690.)

ACCEPT-D (Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes)
Consorzio Mario Negri Sud, Italy (Sponsor – Italian Ministry of Health (Italy))

Study population: 5,170 individuals with diabetes (Type 1 or 2), currently taking or candidate for statin treatment (i.e. LDL cholesterol ≥ 100 mg/dL persisting after 3 months of dietary advice), no history of CVD, aged ≥ 50 years.

Study design: Primary prevention, open-label RCT of low-dose aspirin (100mg) + simvastatin (starting at 20mg/day) versus simvastatin alone, for approximately 5 years
Aim: To evaluate whether, in a setting of controlled LDL cholesterol levels (through treatment with simvastatin), low-dose aspirin is effective in the primary prevention of major cardiovascular events in patients with diabetes.
The primary outcome is a composite endpoint of CV death, non-fatal heart attack, non-fatal stroke, and hospital admission for cardiovascular causes.

PHS (Physicians’ Health Study)

Collaborators: Harvard University, Brigham and Women’s Hospital
Funded by: National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)

Start date – September 1981
Status – Completed December 1996

Study population: 22,071 male American physicians between 40-84 years of age (mean = 53 +/- 9.5 years at enrolment), without a history of CVD or cancer (other than non-melanoma skin cancers), renal or liver disease or having a contraindication to take aspirin or beta-carotene.

Study design: Primary prevention, 2X2 factorial designed RCT (double-blind, placebo-controlled) of 325mg aspirin and 50mg beta-carotene versus placebo on alternate days, provided four possible arms: active aspirin and active beta-carotene, active aspirin and beta-carotene placebo, aspirin placebo and active beta-carotene, or aspirin placebo and beta-carotene placebo. Compliance and health outcomes were measured by questionnaires. Primary endpoints included total cancer, prostate cancer, CVD and eye disease
Aim: To assess the effect on cardiovascular mortality of alternate-day consumption of 325 mg of aspirin and, secondarily, the effect on cancer incidence of alternate-day consumption of 50 mg of beta-carotene.

Conclusion: The aspirin arm was stopped early as aspirin was shown to significantly reduced the risk of a first myocardial infarction (1989. New England Journal of Medicine), although the effect on stroke was inconclusive. Results from the beta-carotene arm did not show harm or benefit. (1996. New England Journal). It is estimated more than 400 papers have been written on findings from this trial.

WHS (Women’s Health Study) Brigham and Women’s Hospital
Collaborators: Brigham and Women’s Hospital. Funded by: National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)

Collaborators: Harvard University, Brigham and Women’s Hospital
Funded by: National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)

Start date – September 1992
Status – Completed February 2005, currently participants are being followed on an observational basis (annual questionnaires)

Study population: 39,876 health professional women aged 45 years and over without a history of cancer or CVD

Study design: Primary prevention, double-blind RCT of alternate day Vitamin E (600 IU every other day) or placebo; and to aspirin (100 mg every other day) or placebo.low-dose aspirin (100mg) versus placebo. Compliance was measured by questionnaires. The primary outcome is a composite endpoint of CV death, non-fatal heart attack, non-fatal stroke, and malignant neoplasms of epithelial cell origin.

Aim: To evaluate the effects of low-dose aspirin and vitamin E in primary prevention of cardiovascular disease and cancer in apparently healthy women aged 45 years and over.

Conclusion: The study showed that aspirin lowered the risk of stroke, but had no effect on the risk of AMI (Ridker PM 2005 NEJM) or cancer (2005 Cook NR et al, JAMA). WHS researchers estimate 400 reports on the study have been published since it began.