Research Article: ASCEND: A Study of Cardiovascular Events iN Diabetes: Characteristics of a randomized trial of aspirin and of omega-3 fatty acid supplementation in 15,480 people with diabetes

Date Published: April 1, 2018

Publisher: Mosby

Author(s): Louise Bowman, Marion Mafham, William Stevens, Richard Haynes, Theingi Aung, Fang Chen, Georgina Buck, Rory Collins, Jane Armitage.


The use of aspirin for the secondary prevention of cardiovascular disease (CVD) is firmly established, and the proportional reductions in heart attacks and strokes appear to be similar in people with and without diabetes. Uncertainty remains about the role of antiplatelet treatments for primary prevention of CVD, and guidelines vary in their recommendations. It has also been hypothesized that long-term aspirin can prevent gastro-intestinal and other cancers.

Between 2005 and 2011, using mail-based methods, 15,480 people with diabetes were randomized to aspirin versus placebo and, in a factorial design, to omega-3 FA supplementation versus placebo. Blood and urine samples were collected to allow baseline stratification by biochemical prognostic variables (e.g. HbA1c, blood lipids). Follow-up is for a median of at least 7 years.

Demonstrating that prophylactic aspirin safely reduces the risk of CVD or cancer in the primary prevention setting, or that omega-3 FA supplementation prevents CVD, would be relevant to hundreds of millions of people worldwide who are currently not receiving such therapies. The results of ASCEND will be reported in 2018.

Partial Text

The Anti-Thrombotic Trialists’ Collaboration (ATTC) demonstrated conclusively that antiplatelet therapy (chiefly aspirin) reduces the risk of myocardial infarction (MI), stroke or cardiovascular death by about one-quarter in people with occlusive vascular disease, including among those who have diabetes.1 However, most of the 3 million people with diabetes in the UK, and the estimated 400 million worldwide,2 do not have manifest vascular disease. The 2009 ATTC individual-patient-data meta-analysis of 95,000 patients in 6 primary prevention trials found that allocation to aspirin yielded a 12% (95% CI, 6%-18%) proportional reduction in occlusive vascular events, mainly due to a reduction in non-fatal MI of about one fifth.3 However, given the approximate 50% proportional increase in the risk of bleeding with aspirin, on average the bleeding hazard counterbalanced much of the benefit in these low-risk primary prevention patients. Among the participants in these primary prevention trials, only about 4% had diabetes and the relative risk reduction among them was similar to that observed in those without diabetes. Consequently, since people with diabetes are generally at 2- to 3-fold higher risk of vascular events than those without it,4 the absolute risk reduction with aspirin is likely to be greater than for healthy volunteers. However, the ATTC analyses also found that people with diabetes had a higher risk of both major extra-cranial bleeds (rate ratio [RR], 1.55; 95% CI 1.13–2.14) and of hemorrhagic stroke (RR, 1.74; 95% CI, 0.95-3.17, respectively) compared to those who did not have diabetes irrespective of aspirin allocation.3

There remains continuing clinical uncertainty about whether or not aspirin should be recommended for the primary prevention of cardiovascular events in people with diabetes.13 This is reflected in the differing and changing recommendations in cardiovascular prevention guidelines. When ASCEND was designed, the American Diabetes Association recommended aspirin use for primary prevention in people with diabetes with one additional risk factor28 but, at that time, the UK and European guidelines were more circumspect.29., 30. More recently, both the 2015 UK National Institute for Health and Care Excellence (NICE) guideline for type 2 diabetes31 and the 2016 European Guidelines32 have advised not offering antiplatelet therapy for adults with type 2 diabetes but without cardiovascular disease. By contrast, the US Preventive Services Task Force now recommends low-dose aspirin for the primary prevention of cardiovascular disease and colorectal cancer in adults aged 50–59 years who have a 10-year cardiovascular risk of at least 10% and are not considered at increased risk for bleeding, irrespective of their diabetes status.33

The current global epidemic of diabetes makes robust evidence about the effects of low-cost prophylactic interventions especially important. For example, demonstrating that primary prevention with aspirin prevents cardiovascular events or cancers, and that the benefits outweigh the risks of bleeding, would be relevant to some hundreds of millions of people worldwide who are at risk of such events but are currently not taking low-dose aspirin. On the other hand, if the risks of serious bleeding outweigh any benefits then these risks could be avoided by the very large numbers of people who are currently using aspirin for primary prevention.




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