CaPPtain's Blog: John Burn, May 2021

CaPPtain's Blog: Taking aspirin and getting old

Two papers have been published recently based on the ASPREE trial^1,2; ASPirin in Reducing Events in the Elderly recruited 19,114 people aged 70 and over in Australia and the USA (65 and over for US minorities) to receive 100mg aspirin or an identical placebo.  They have now been followed for an average of 4.7 years.  The papers are a follow up analysis of the earlier trial report in 2018³. 

Given the extensive evidence, gathered over 30 years, that regular aspirin use reduces the burden of  colorectal and other cancers, the original ASPREE report was a surprise as it suggested there might be more cancers in the people randomised to receive aspirin.  This new information shows that, so far, the overall number of cancers in the two groups is about the same.  However, the people in the aspirin group who developed cancer did less well.  There were more cases of cancers that had spread and more deaths in the aspirin group. In both cases, there were about 5 in the aspirin group for every 4 in the placebo group. 

Back in the 90's, when a long series of studies reported aspirin was probably protective, a study led by  Dr Paganini-Hill based on older people in residential care homes, reported a higher cancer risk in the over 80s⁴.

As expected in the ASPREE trial, there were more cases of bleeding events.  The main difference was due to ulcers in and around the stomach with about 8 cases in the aspirin group for every 5 in the placebo group, though the only two who died were in the placebo group.  There was a wide variation in bleeding risks across the people who took part; for example the chance of a bleed in a fit 70 year old was about 1 in 400 over five years whereas the risk in an 80 year old with risk factors was 1 in 20 over five years.  The main risk factors apart from age were smoking, being significantly overweight and having kidney disease or high blood pressure.

What are we to make of this new information? The first thing to say is that it doesn't change the overall plan in CaPP3.  The protection against cancer in CAPP2 was very clear and there was no difference between the two groups when it came to major side effects.  This was because the average age of the people in the study was only 45 when they joined.  The risk of bleeds caused by aspirin rises sharply from about 65 years of age onwards.  It's also probably worse in someone who starts aspirin at this older age, as people who have been on aspirin a long time seem to have fewer bleeds at any given age.

As for the effect on cancer, again the result wasn't a complete surprise.  Given the observations by Paganini-Hill and colleagues, there was already a suggestion that starting people on aspirin after the age of 70 might not be as successful in preventing cancers.  It's also important to remember that all studies have suggested that it takes about 5 years before the preventive effect of aspirin becomes apparent, and in the Women's Health Study where participants took a 100mg of aspirin every other day, the benefit didn't appear until 10 years after starting the trial, so there is still time for the ASPREE trial to show long term benefit.  It is possible, though, that the effects of getting older may make aspirin become less effective as we age.  Our group is now collaborating with Dr Laura Greaves, an expert in mitochondrial genetics and ageing, at Newcastle University to explore this possible link. 

Finally, some definite good news.  The American Society of Clinical Oncology ASCO has declared our CAPP2 paper last year as the most significant advance in cancer prevention of 2020⁵.

John Burn
May 2021

References:

1.     McNeil JJ, Gibbs P, Orchard SG, et al. Effect of Aspirin on Cancer Incidence and
Mortality in Older Adults.Journal of the National Cancer
Institute.2021;113(3):258-265.

2.     Mahady SE, Margolis KL, Chan A, et al. Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial.Gut.2021;70(4):717-724.

3.     McNeil JJ, Nelson MR, Woods RL, et al. Effect of Aspirin on All-Cause Mortality in the Healthy Elderly.New England Journal of Medicine.2018;379(16):1519-1528.

4.     Paganini-Hill A. Aspirin and colorectal cancer: the Leisure World cohort revisited.Prev Med.1995;24(2):113-115.

5.     Smith SM, Wachter K, III HAB, et al. Clinical Cancer Advances 2021: ASCO's Report on Progress Against Cancer.JClinOncol.2021;39(10):1165-1184.