CaPPtain's Blog: John Burn, August 2019

Well it has taken three decades but we now have an official recommendation that doctors should offer aspirin for at least two years to people with Lynch syndrome. The good news is that the National Institute for Healthcare and Clinical Excellence (NICE), has responded to our submission in 2017 with this recommendation that is now out for public review over the coming month (see web links below). We will reinforce the decision with a response to say that our new data based on double the length of follow up used in the CAPP2 2011 paper, shows continued protection. We are in the process of submitting the CAPP2 10 year follow up for publication.

The downside is that doctors have a relatively negative view of aspirin due to the side effects. These can include life threatening bleeds from ulcers. It has become increasingly clear that these side effects are much more common in old and frail people so we need to consider stopping or greatly reducing aspirin intake once we get past pension age. The problems experienced in Australia and USA among the over 70s in the recently reported ASPREE trial, who were randomised to receive aspirin versus placebo, were made worse by the fact that many had not taken aspirin before. The side effects tend to decrease as people get used to the aspirin. Side effects can also be reduced by taking an acid blocker and by getting rid of Helicobacter pylori, a common stomach infection.

However, we can't get away from the fact that there is a small but significant chance of side effects if people take aspirin, so the benefits need to be clear. In the case of people with Lynch syndrome, the risk of colorectal cancer is much higher than the general population so the "risk benefit ratio" is clearly in favour of taking the tablets.

The big question is 'what is the best dose of aspirin?' To answer this we are relying on the 1882 people who signed up to CaPP3, which is comparing the effect of three different doses of aspirin. It's vital that we keep in touch with these volunteers over the coming years. Our first recruit started in 2014 and reaches the five-year mark in October of this year. We will continue to follow their progress, as we will all the people who joined up unless they actively tell us to stop. This is because the experts put great store in the analysis of all the people who started, not just the people who stay in to the end of the study. This so-called "intention to treat" analysis is the most robust way of comparing the groups. We hope that people who signed up for CaPP3 will stick with us to the end of the five years but even if they don't, we need to know what happened next. If we lose contact, the trial is weakened and we will be left guessing what the optimal dose is for the future. This is where the CaPP3 teams, both national and international, are key to gathering this follow up data and entering the data on to MACRO. It is essential to the study that all follow up and contact information is entered on to MACRO for study analysis. Do let us know if you are having problems contacting study participants and/or data entry.

We are now being asked, 'what should people do once they have completed the CaPP3 study?' The obvious answer is to continue taking aspirin. A low dose aspirin (75-100mg) may be enough but two low dose aspirin or half a standard (300mg) aspirin morning and night is a good guide for people between 25 and 65. NICE state 'a commonly used dose in current practice is either 150mg (75mg x 2) or 300mg, sometimes depending on other gastrointestinal risk factors.' Both CAPP2 and CaPP3 have used enteric coated aspirin. It's important to remember that this is a best guess. It may be that we find that the people on the bigger dose of two aspirins a day (600mg) will do the best in CaPP3. It's also important to remember that the people who took that dose of aspirin in CAPP2 did not have significantly more side effects than the people on placebo tablets, probably because they were younger than the people who usually turn up at the hospital with aspirin side effects.

Thanks again to all the people taking part in CaPP3 and to the army of doctors, nurses and scientists who make it possible.

John Burn
6th August 2019

Web links:

https://www.nice.org.uk/news/article/offer-daily-aspirin-to-those-with-inherited-genetic-condition-to-reduce-the-risk-of-colorectal-cancer

https://www.cancerresearchuk.org/about-us/cancer-news/news-report/2019-08-02-daily-aspirin-reduces-bowel-cancer-risk-in-people-with-lynch-syndrome-says-nice

http://www.pharmatimes.com/news/aspirin_should_be_offered_to_lynch_syndrome_patients_1296182

https://www.telegraph.co.uk/science/2019/08/01/prescribe-aspirin-prevent-common-cancers-doctors-told/?fbclid=IwAR1DpbYrzfvGKyQtNyJ8G5HdonC39T80j2cpSjE8RF85P9LN92Y9FiHUV2E