CaPPtain's Blog

  • CaPPtain's Blog: John Burn, May 2021

    posted on Thursday, 27th May 2021

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    CaPPtain's Blog: Taking aspirin and getting old

    Two papers have been published recently based on the ASPREE trial1,2; 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


    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

    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.

  • CaPPtain's Blog: John Burn, December 2020

    posted on Monday, 4th January 2021

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    As a challenging year draws to a close, I'm pleased to report that CaPP3 has been able to continue operating almost as normal. Some clinic appointments have been delayed but we have been able to maintain the core operation and issue prescriptions across the system.

    In May 2021 we will reach a major trial milestone as the last recruits reach the end of the two years on blinded treatment. From then on, all people still in the trial will know what aspirin dose they have been allocated. You will remember the main purpose of this trial is to see if lower doses of aspirin are as protective as the 600mg dose we proved was effective in CAPP2. This is important because the side effects of aspirin increase with bigger doses. The two years of blinded treatment at the start are designed to collect reliable information about side effects on the three doses (600, 300 & 100mg aspirin), without any bias.

    The main endpoint is counting how many colon and other cancers develop over the five years and beyond. In the meantime, the National Institute of Clinical and Care Excellence -  NICE NG151, has now recommended that everyone diagnosed with Lynch syndrome is advised by their doctors that aspirin is recommended to reduce the risk of cancer. This guidance has also gone out from NHS England to the Cancer Alliances across the country. The NICE guidance recognises that we don't know the best dose yet and that our CaPP3 trial will provide that answer. I am now recommending that people under 70kg take 150mg a day (a half standard tablet or two cardio aspirins) and people over that weight take 300mg or one standard aspirin a day until our intrepid CaPP3 community provide the answer in 2024.

    Meanwhile, as we prepare for another Covid-19 shadowed year, I am pleased to say that there is now evidence that aspirin protects people from some of the worst effects of the virus. This is probably a combination of its anti-inflammatory effect and prevention of blood clotting. One of the surprising discoveries earlier this year was that Covid-19 patients have "sticky" blood which was blocking small blood vessels. You may recall that there were claims in the Spring that aspirin like drugs may cause a problem with Covid-19. I am now even more sure that it was "fake news" and people on CaPP3 can be reassured that staying in the trial is not a cause for concern.

    The UK led RECOVERY trial now has an aspirin arm, investigating aspirin as a possible treatment for Covid-19. Also a scientific report* from Baltimore looked at whether people were taking aspirin when they were admitted to hospital with Covid-19, and compared their outcomes to those who were not. The people on aspirin did better. This is not as good as a proper randomised trial but it's encouraging. I've added the details of the paper by Jonathan Chow and colleagues at the end if you would like to read the paper.

    I updated the virtual UK Cancer Genetics Group meeting last week about CaPP3, where I was able to thank colleagues across the UK and beyond for their continued support. May I take this opportunity to thank again all the people who have been in or are still taking part in the CaPP3 trial as well as all the study teams in the UK and internationally. Without your help we could never solve the problem of choosing the best dose of aspirin to prevent cancer in Lynch syndrome.

    Enjoy the festive season as best you can, keep safe and all best wishes for 2021!

    John Burn

    18th December 2020

    *Anesthesia & Analgesia Journal      Jonathan H. Chow et al 2020
    Aspirin Use is Associated with Decreased Mechanical Ventilation, ICU Admission, and In- Hospital Mortality in Hospitalized Patients with COVID-19 DOI: 10.1213/ANE.0000000000005292

Latest News

  • 17



    Last Newcastle Recruit

    posted on Wednesday, 17th April 2024
    Last Newcastle Recruit

    "Delighted to see Robin, our last Newcastle recruit to CaPP3 for his five year follow up" - Professor Sir John Burn

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  • 04



    Lynch Choices website: now inviting patients to complete digital feedback surveys

    posted on Thursday, 4th April 2024

    Lynch Choices have started sharing the beta version of the Lynch Choices patient decision support website, containing information including personalised cancer risks via a link to the Prospective Lynch Syndrome Database, patients stories and signposting to resources and charities, to complement shared-decision making with healthcare professionals. 

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