posted on Monday, 16th March 2020
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Urgent CaPPtain's Blog: Covid-19
On 13th March, the French Health minister, who is also a qualified
doctor, advised people to use paracetamol to treat fever associated
with Covid-19 infection as it was possible that anti-inflammatory
drugs like ibuprofen and aspirin might prolong the disease but
diminish the immune response. No evidence has yet been published
and this opinion seems to be based on observations in other
infections.
In contrast, there is speculation that the severe lung problems
sometimes associated with the new coronavirus are the result of an
over-reaction of the immune system, a process known as a cytokine
storm. There have been rapid publications exploring use of a
variety of drugs used to suppress inflammation. A new formulation
of aspirin which is combined with a short chain fatty acid called
triacetin to make it soluble is going to be tested as a treatment
in people with a Covid-19 infection.
While more information is gathered, my proposal is that people
on CaPP3 can continue to take their aspirin but should stop if they
develop symptoms and restart once they recover. If, however, the
mixed messages cause concern, it is, of course, acceptable for
anyone to temporarily suspend their treatment until the emergency
subsides. A three-month period would seem reasonable.
John Burn
16th March 2020
posted on Thursday, 27th February 2020
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I saw my first daffodils this week. Spring is coming soon
and with it good news.
The first event of note is the completion of the
NICE*
approval of aspirin as a preventive agent in Lynch
syndrome. This guidance became official in January,
complementing the decision of the British Society of
Gastroenterology to make the same
recommendation and international endorsement via the formal
voting system among members of the European Hereditary Tumour
Group. Aspirin is still not formally licensed for cancer
prevention in the UK but we are working on that too.
Meanwhile doctors can prescribe aspirin, if they agree with this
guidance.
The NICE endorsement will, hopefully, be stronger following the
imminent publication by the Lancet of our latest paper documenting
the planned CAPP2 trial 10 year follow up, supplemented by registry
data in England, Wales and Finland for the second decade. The
bottom line is that the effect of aspirin (600mg daily) on
colorectal cancers (CRC) is even more secure, with a significant
reduction with the rigorous method of Hazard Ratio on the basis of
Intention to Treat. In plain English, this means that even when we
count only the first colon cancer and include all the people
allocated to the aspirin group, even if they dropped out early,
there are significantly fewer cancers in the people in the aspirin
group. When we focus on people who actually took the two
aspirins a day for two years and including all their primary
colorectal cancers in the analysis, the relative risk is 0.50. That
means they had half as many colorectal cancers over an average of
ten years.
There were also fewer non-CRC Lynch syndrome cancers but
overall, the statistical significance was lost by 10 years.
This probably means that the effect is not as long lasting and may
not apply to all types of cancer. We do, however, have new
information on resistant starch, the diet supplement in
CAPP2. Those of you who follow me on twitter (@CaPP3) will have
seen that I reported to the recent Clinical Genetics Society
meeting in Cambridge that the non-CRC Lynch cancers were reduced in
the people who were given the active diet supplement compared to
the placebo group.
CaPP3 is still on course and has become even more important as
NICE recognise the importance of our ongoing trial. They
endorsed our suggestion that while we await the result of CaPP3 the
"best guess" is that people should take 150mg (two "cardio"
aspirins) if they are below 70kg (11 stone) and 300mg (a standard
aspirin) if they are over that weight. This is based on our
overall reading of the literature. I hope people who are in
CaPP3 will continue for the five years, as planned on their study
dose so that we can see if the different doses do have a different
effect. The first recruit to the trial, Nick from Newcastle,
has now completed his five years along will several more early
participants while the last recruit will complete the 2 year
"blind" phase next spring. That means we still have four
years to wait but it will be worth it. Some
experimental work by Rick Boland and colleagues in America has
supported the CaPP3 plan; they simulated the three doses using
cancer cells in the laboratory and saw a bigger effect with the
higher doses. On the other hand, of course, we expect more
side effects with the higher doses so there will need to be a
careful assessment of the pros and cons at the end of the
trial. If you are still in CaPP3, thanks again! Please keep
in touch. We are always keen to hear from you.
*NICE stands for the National Institute for Health and Care
Excellence
John Burn
27th February 2020