Professor El-Omar has chosen Dr Suzanne Mahady, Gastroenterologist & Clinical Epidemiologist Senior Lecturer, School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia to do the next #GUTBlog.

The #GUTBlog focusses on the latest paper “Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial” which was published in paper copy in GUT in April 2021. Dr Mahady is the senior author on this paper.

Dr Mahady writes:

“Despite continuing advances in therapy, gastrointestinal bleeding remains a life-threatening condition. People who experience a serious bleeding event have an estimated mortality of around 10%, a figure that has remained stagnant for more than fifty years. Aspirin is well known to cause gastrointestinal bleeding and while the mechanisms are well understood, the exact risk has not been clearly quantified. This is particularly important in older people who have a higher risk of mortality and are more likely to be aspirin users.

Estimating the risk of an intervention like aspirin is particularly important when it is prophylactic i.e. started to prevent a future adverse event, in individuals who are perfectly well to begin with. The use of aspirin to prevent the first heart attack or stroke has been embraced enthusiastically by patients and physicians alike for many years, despite questionable evidence of benefit and little information on the harms.

Our ASPREE (Aspirin in Reducing Events in the Elderly) trial provided us with an ideal data set to quantify bleeding risk with aspirin in older people. This landmark trial set out to answer the question “Does aspirin promote healthy ageing in older people?” More than 19,000 older people living in the community in Australia and the United States were randomised to aspirin or placebo and followed for nearly 5 years for endpoints including death, disability and bleeding.

The findings? There was no overall benefit for aspirin in reducing death or disability in older people. This result essentially debunked decades of strongly held belief and prompted vigorous discussion globally and revision of guidelines on aspirin as primary prevention. Just as importantly, there was a clear signal of harm in aspirin users, with more serious bleeding events.

Using data from the ASPREE trial, we set out specifically in this paper published in GUT to quantify bleeding risk and identify other risk factors. We found that aspirin increased the risk of a major bleeding event requiring blood transfusion or hospitalisation by approximately 60%.  Furthermore, that risk was apparent as soon as people started taking aspirin and did not disappear over the course of the study, contradicting the long-held view that the stomach might ‘adapt’ to aspirin and the bleeding risk attenuate with time.

We identified age as the other key risk factor for serious bleeding. Compared to a well 70-year-old, the bleeding risk in those aged over 80 was more than threefold, and even higher when you add in smoking, kidney disease and use of other non-steroidal anti-inflammatory drugs. Somewhat surprisingly, there were only two fatal gastrointestinal bleeding events, both in the placebo group.

How can these data help? They provide robust and generalisable evidence of the exact risk of bleeding with prophylactic aspirin use in older people and should prompt discussions on the appropriateness of aspirin use. Other identified risk factors may provide modifiable targets to prevent a bleeding episode.

It is important to stress that our results do not apply to aspirin used for secondary prevention, that is, when a person has experienced an initial event like a heart attack or stroke. In secondary prevention, the benefit of aspirin clearly outweighs the risk.

Like all research, our results have prompted further questions. Next, we aim to follow our cohort for a further 5 years to evaluate the long-term impact of a serious gastrointestinal bleed and determine if people who have a bleeding event have different health outcomes to those who do not. Despite its frequency, there is still a lot to learn to prevent gastrointestinal bleeding and improve mortality outcomes.”

Dr Suzanne Mahady, Gastroenterologist & Clinical Epidemiologist Senior Lecturer, School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia