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
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.
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