Prevention - ASCEND

The clinical question

People who have had a heart attack or stroke are often prescribed a daily low dose of aspirin. This can help prevent the formation of blood clots that can cause these conditions. But aspirin can have side effects, such as an increased risk of bleeding. So it’s not usually recommended for preventing a heart attack or stroke happening in the first place, in generally healthy people (primary prevention). However, there has been some debate over whether aspirin should be prescribed as primary prevention for people with diabetes, who have a high risk of cardiovascular events.

Similarly, there is some evidence that oils rich in omega-3 fatty acids (such as fish oils) may reduce the chances of a second heart attack. But whether these oils could also help in the primary prevention of heart and circulatory complications in people with diabetes was unclear.

So Professor Jane Armitage, Professor Louise Bowman and their team at the University of Oxford designed the ASCEND trial (‘A study of cardiovascular events in diabetes’). This large trial aimed to test whether a daily aspirin tablet and/or a fish oil capsule could help to prevent heart attacks and strokes in people with diabetes. The BHF funded the trial over 14 years. 

What did the study involve?

Between 2005 and 2011, the trial recruited over 15,000 people with diabetes from around the UK who did not have problems with their heart or circulation at the time they joined the study. Participants were randomly assigned to:

• Take either 100 mg aspirin daily or a placebo tablet. 

• They were then randomly assigned again to receive either a capsule of omega-3 fatty acids daily or a placebo capsule containing olive oil. 

The participants were followed up every six months, for an average of 7 years:

• Participants completed questionnaires about their health. 

• The researchers also tracked the participants’ health records to flag if they suffered a ‘serious vascular event’, such as a heart attack or stroke, or a ‘serious side effect’, such as bleeding in their digestive system. 

Previous studies had suggested that aspirin might protect against the development of cancers in the gut, with the effects increasing over time. The team therefore expanded their analysis to track whether taking aspirin and/or fish oil affected the participants’ likelihood of developing cancer.

What did the study show?

• Taking a daily aspirin reduced the risk of having a serious heart or circulatory event (such as a heart attack or stroke) by about 12% in people with diabetes.

• This was outweighed by an increased risk of having a major bleed (increased by 29%). 

• Although taking an omega-3 supplement was safe, it seemed to offer no benefit to the participants.

• There were no differences in the rate of cancers developing across any of the groups.

Why is the study important?

This large trial provided conclusive evidence that doctors should not recommend taking a daily aspirin to reduce the risk of heart and circulatory conditions in people with diabetes as primary prevention. Professor Armitage explained the implications of the results at the 2018 European Society of Cardiology Conference in Munich: "Even though we showed clearly that aspirin reduces the risk of vascular events, it also increased the risk of major bleeds, mainly from the gastrointestinal tract, so overall there was no clear benefit. It had been suggested that low-dose aspirin might protect against cancer, but we saw no reduction in any cancers. We are continuing to follow the participants to see whether any benefits appear later."

In addition, the results of the trial suggest that taking a fish oil supplement does not benefit the cardiovascular health of people with diabetes. Professor Louise Bowman, who co-led the study, said:

People in the UK spend approximately £60 million a year on fish oil supplements, and the impact of its production on the environment is a current source of debate. The results of this study support the idea that people should instead focus on having a broadly healthy diet - including oily fish - to help protect their cardiovascular health.

Study details

"ASCEND: A Study of Cardiovascular Events in Diabetes" 
Award reference:  SP/14/3/31114, SP/08/010/25939, PG/05/013/18296, SP/03/002/15675
Principal Investigators: Professor Jane Armitage & Professor Louise Bowman, University of Oxford
Trial registration: NCT00135226

Publication details

Aspirin results - Bowman L, Mafham M, Wallendszus K, et al. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med. 2018;379(16):1529-1539.

n-3 fatty acid results - Bowman L, Mafham M, Wallendszus K, et al. Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus. N Engl J Med. 2018;379(16):1540-1550.