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
posted on Tuesday, 16th June 2020
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Well, we finally got there. The 10-year follow up paper on
the CAPP2 study is now published in the
Lancet (13th June 2020)*. It may seem a long
time since the
2011 CAPP2 paper but we wanted to extend the analysis to
include the second decade for those who started earliest. Our aim
was to see if the protective effect seen in our 2011 analysis
persisted for more than the average of 5 years since starting in
the trial.
The important take home message is that the effect was even
clearer than in 2011, the protective effect of aspirin against
colorectal cancer has persisted in this long-term follow up, for up
to 20 years. The gold standard test in any randomised trial
is to demonstrate a significant difference on "Intention to
Treat". This means that everyone who started in the aspirin
part of the trial is included, whether or not they stuck with the
treatment. This is a very hard test and the result did not
reach the necessary levels of statistical significance last time in
2011, but this time it did, providing convincing evidence that the
effect is due to an overall cancer preventative property of
aspirin.
When asking how big the difference was, known as "efficacy", it
still is sensible to look at all the cancers in the LS folk who
took the treatment for the planned two years at least. We
judged this as people who had taken a total of 1400 trial tablets
over that time period. The statistical analysis of this group
showed there were half as many colon cancers in those who took
aspirin regularly during the trial. Obviously, many may have
taken aspirin in the subsequent years after completing the CAPP2
trial but this might apply to all the participants. The only
difference between the two groups was the couple of years on the
trial when one group had real aspirin tablets and the other had
placebo tablets.
For those of you who like the real numbers, here they are:
427 people took aspirin and 40 of them got colon cancer. Two
of them got colon cancer twice, so there were 42 bowel cancers over
an average of 10 years follow up. 434 people were in the
placebo group and 58 of them got colon cancer, some more than once
making a total of 71 bowel cancers, that's 29 more than the aspirin
group.
The
UK National Institute for Healthcare and Clinical Excellence
(NICE) announced in January 2020, based on the evidence from
the 2011 CAPP2 paper, that aspirin should be recommended to all
adults with Lynch syndrome. NICE noted that the CaPP3 study
would provide information on the optimal dose but in the meantime
supported a lower dose. We are recommending 150mg daily for
people of average size, less if you are of small build and more if
you are heavier. This is based on the
recent work of Peter Rothwell reanalysing the old trial data
and,
on our paper, looking at the higher cancer risk in LS people
who were overweight. The Australian authorities have
now endorsed use of aspirin in LS and our European survey organised
by the European Hereditary Tumour Group has just been accepted for
publication and shows general professional support. It is
still a recommendation and we need to get cancer prevention listed
for aspirin in the British National Formulary.
The other big news is, of course, theCovid-19 pandemic. We
are aware that some participants in CaPP3 stopped their aspirin
after newspaper reports that non-steroidal anti-inflammatory drugs
might make the illness worse. We now know this is not
true. In fact, a couple of Covid-19 trials have now started
including aspirin as a treatment because it has been shown that
excessive clotting is part of the illness. We are planning an
aspirin trial in early Covid-19 cases in Newcastle too. The
take home message is thatIT'S OK TO TAKE ASPIRIN! People in
CaPP3 can return to their prescribed aspirin. As follow up
appointments are arranged, we will need to know who stopped taking
their aspirin and for how long, so we can include this in the final
CaPP3 analysis in 2024.
If you have Lynch syndrome and are not on the trial, then this
blog and the CAPP2 Lancet paper will support discussions with your
doctor to discuss regularly taking aspirin. Make sure your
blood pressure is normal and that you don't have a treatable
Helicobacter pylori infection in your stomach, as many people still
do. If clear, then take some aspirin to reduce your colon
cancer risk.
Thanks again to all the people who are taking part in CaPP3. And
a special thank you to the CaPP3 participants who have completed
the five years of study aspirin. You will be receiving a personal
thank you letter from the study (once approved by the ethics
committee). The CaPP3 study will keep in contact with you annually
after your Year 5 contact. As we have shown in CAPP2, your
participation in these trials is essential if we are to change
clinical practice. We still need to know the best dose, so if you
are in CaPP3, please keep taking the study aspirin.
John Burn
16th June 2020
*Additional links
https://www.ncl.ac.uk/press/articles/latest/2020/06/10yearaspirinstudy/
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30973-9/fulltext#.XuOQnsE_khU.twitter