Ongoing Aspirin Studies | Aspirin Studies in Primary Prevention

As part of its ongoing commitment to working with the scientific community to further explore the benefits of Aspirin as a cornerstone of CVD prevention, Bayer is supporting additional clinical trials, that further the science of Aspirin. These independent, investigator-initiated trials are designed to increase understanding the lifesaving and preventive benefits of Aspirin in special populations, including patients with diabetes, asymptomatic atherosclerosis, venous thromboembolism (VTE), and the elderly. Summaries of six of the many ongoing studies of aspirin are presented below.

ASCEND – A Study of Cardiovascular Events in Diabetes

Jane M Armitage, BSc, MBBS, MRCP, FFPH, Principal Investigator, Clinical Trial Service Unit, University of Oxford

The ASCEND trial will evaluate whether low-dose, enteric-coated Aspirin, with or without omega-3 fatty acids, lowers the risk of CVD events in diabetic patients who do not yet have occlusive arterial disease. ASCEND will recruit 10,000 patients and follow them for up to five years. Men and women at least 40 years old with diabetes Type I or II will receive either Aspirin alone, Aspirin plus omega-3 fatty acid supplements, omega-3 supplements alone, or placebo (approximately 2,500 patients per treatment cohort). Primary study endpoints include incidence of serious CVD events (fatal or non-fatal MI or ischemic stroke). Additional analyses will include comparative incidences of serious vascular events or revascularizations, confirmed cerebral hemorrhage, all-cause mortality, total coronary events, non-hemorrhagic stroke, venous thromboembolism (VTE), total and site-specific cancers, and hospitalizations for various other causes.

POPADAD – Prevention of Progression of Asymptomatic Diabetic Arterial Disease

Prof Jill Belch, Department of Medicine, Ninewells Hospital & Medical School

The POPADAD trial has completed study activity and publication of trial results is expected in late 2007. POPADAD was a eight-year trial that evaluated whether low-dose, enteric-coated Aspirin, alone or in combination with antioxidant therapy, would reduce the incidence of CVD events in diabetic patients with asymptomatic peripheral arterial occlusive disease, and do so in a cost-effective manner. More than 1200 diabetic patients with reduced ankle brachial pressure index were recruited and randomized to Aspirin alone, Aspirin plus antioxidants, antioxidants alone, or placebo (approximately 300 patients per cohort). Two hierarchical primary endpoints are sought including 1) coronary heart disease and stroke death plus non-fatal MI and stroke, and above-ankle amputation; and 2) coronary heart disease and stroke death. Secondary endpoints include all-cause mortality, non-fatal MI, other vascular events, and cost-effectiveness of intervention.

J–PAD – Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes

Hisao Ogawa, MD, Kumamoto University, Kumamoto City, Japan

Yoshihiko Saito, MD, Nara Medical University, Nara, Japan

The J–PAD study is a multi-year evaluation of the safety and effectiveness of low-dose Aspirin in preventing initial CVD events in Japanese patients with Type II diabetes. Approximately 2,500 patients were randomized to receive low-dose Aspirin or placebo. The study continues until yearly statistical analysis determines a divergence in the risk of developing primary events. The primary study endpoint is cardiovascular death, directly or indirectly related to myocardial infarction or ischemic heart disease. Other CVD events are being evaluated as secondary endpoints, including non-fatal coronary events (non-fatal MI, angina, and silent MI), non-fatal cerebrovascular events (cerebral infarction, hemorrhage, or transient ischemic attack), and arteriosclerotic disease requiring treatment or surgery.

JPPP – Japanese Primary Prevention Project with Aspirin in Elderly Patients with One or More Risk Factors of Vascular Events

Yasuo Ikeda, MD, Principal Investigator, Keio University School of Medicine, Tokyo, Japan

The JPPP study is a four to five year study evaluating the ability of low-dose, enteric coated Aspirin to prevent CVD events in elderly Japanese patients with hypertension, hyperlipidemia, and/or diabetes. JPPP is a nationwide (Japan), centrally randomized, controlled trial comparing Aspirin and placebo in approximately 10,000 patients aged 60-85 years. Primary endpoints include a composite of CVD death, non-fatal cerebral stroke, and non-fatal MI. Additional study endpoints that will be evaluated include non-CVD deaths, angina pectoris, transient ischemic attacks, surgery or medical intervention for arteriosclerotic disease, and bleeding complications.

AAAT – Aspirin Asymptomatic Atherosclerosis Trial

Gerry Fowkes, Ph.D., FRCPE, FFPHM, The University of Edinburgh, United Kingdom

The AAAT study will evaluate the ability of low-dose, enteric-coated Aspirin to prevent initial CVD events in patients with asymptomatic atherosclerosis as determined by decreased ankle brachial pressure index. The eight-year trial expects to randomize more than 3,000 patients, including men and women 50-79 years of age to Aspirin or placebo. The primary study endpoints are myocardial infarction and stroke, both fatal and non-fatal. Secondary endpoints for AAAT are occurrence of angina, intermittent claudication, and all-cause mortality.

ASPREE – Aspirin in Reducing Events in the Elderly

Mark R Nelson, Monash University, Melbourne, Australia

Bayer is conducting the ASPREE trial to determine the safety and effectiveness of low-dose, enteric-coated Aspirin for preventing primary CVD events in elderly men and women, aged 70 or older. Eligible patients will enter a baseline period to confirm their compliance with dosing instructions, then those demonstrating 85-104% compliance rates will be randomized to either Aspirin or placebo and followed for up to five years. Approximately 20,000 patients will be randomized between Aspirin and placebo. Primary study endpoints are occurrences of major CVD events (fatal and non-fatal). Secondary and tertiary endpoints include all-cause dementia, cognitive decline, clinically significant bleeding, total mortality, fatal and non-fatal cancers, transient ischemic attacks, hemorrhagic stroke, hospitalizations for various causes, and quality of life and cost-effectiveness assessments.

SILENCE – Silent Infarction Longitudinal Evaluation on New Cardiovascular Events

Vittorio Di Piero, Ph.D., Stroke Unit and Headache Clinical, University of Rome, Italy

The SILENCE study is being carried out in Italy assessing the ability of low-dose, enteric-coated Aspirin to safely prevent appearance of new silent cerebrovascular lesions, as well as the occurrence of strokes and transient ischemic attacks. Men and women aged 45 or older with at least one silent cerebral infarction (MRI evidence) will be recruited into the study. A total of approximately 350 patients will be randomized to receive either Aspirin or placebo and will be followed for up to four years. The primary study endpoint is the combined incidence of ischemic stroke, TIA, and new silent infarctions as assessed by MRI. Secondary endpoints to be evaluated are incidence of new occurrences of cognitive decline and combined CVD events (total mortality, CV mortality, non-fatal MI and non-fatal stroke).

ASPIRE – Aspirin to Prevent Recurrent Venous Thromboembolism (VTE)

John Simes, MD, MSc, NHMRC Clinical Trials Centre, Sydney, Australia

Timothy Brighton, MBBS, FRCPA, FRACP, MD, St George Hospital, Sydney, Australia

John Eikelboom, MBBS, Royal Perth Hospital, Australia

The ASPIRE trial will examine the ability of low-dose, enteric-coated Aspirin to prevent recurrent symptoms in patients with VTE who have been treated with warfarin for a period of three to12 months. The multinational study plans to enroll 3000 patients, to be randomized equally to Aspirin or placebo, and followed for an average of three years. The primary study endpoint is objectively diagnosed symptomatic VTE or fatal pulmonary embolism. In addition, bleeding events, all-cause mortality, and a composite of symptomatic VTE, myocardial infarction, stroke, or CVD death will be evaluated as secondary endpoints. Sub-study analyses will include incidence of postphlebitic syndrome, and cost effectiveness measurements.

WARFASA – Warfarin and ASA: Aspirin after six Months of Oral Anticoagulants for the Prevention of Recurrent VTE and CV Events in Patients with Idiopathic VTE

Giancarlo Agnelli, MD, University of Perugia, Italy

The WARFASA trial seeks to determine whether low-dose, enteric-coated Aspirin prevents recurrent symptomatic VTE and CVD events when given over a two-year period following initial six months of warfarin therapy. This European multinational trial will recruit approximately 1400 patients randomized to either placebo or Aspirin, and followed for a minimum of two years. The primary study endpoint is comprised of combined CVD events and recurrence of VTE (i.e., the sum of confirmed recurrent symptomatic VTE, fatal pulmonary embolism, non-fatal myocardial infarction, CVD death, and sudden otherwise unexplained death). Secondary endpoints will be bleeding events, all-cause mortality, and newly diagnosed cancer. Exploratory analyses will include individual parameters of the combined primary endpoint.

Aspirin is approved for varying indications in varying countries by varying regulatory bodies. Bayer is not promoting any unapproved use for Aspirin^®.
Please check the approved labeling in your country.