Aspirin for everyone older than 50?
BMJ 2005; 330 doi: https://doi.org/10.1136/bmj.330.7505.1440 (Published 16 June 2005) Cite this as: BMJ 2005;330:1440
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Ellen C G Grant notes in her Rapid Response of 22 June that ‘there is
some evidence of adverse effects of foods with a high salicylate content’,
as suggested by Dr Ben Feingold.
Perhaps I could bring personal experience to bear; I am allergic to
aspirin et al, and have life-threatening allergic responses to azo dyes,
coal tar dyes and benzoate preservatives. For obvious reasons I totally
exclude them from my diet, and have in the past tried excluding foods
naturally high in salicylates.
The difficulty is that salicylate levels vary hugely in plants
depending on a host of factors. The herbalist’s injunction, for example,
to harvest a specific plant by the light of the full moon, say, is not
mumbo jumbo; it really does make a difference. Excluding naturally
occurring salicylates is a great deal harder than it looks, and no
significant conclusions can be drawn from the various attempts to do so.
Incidentally, a much greater source of danger is the pharmaceutical
manufacturers’ insistence on dyeing their products in pretty colours, and
lacing them with large amounts of preservatives. I am unable to think of
any rational explanation of how they manage to persuade regulators that
these can be accurately described as inactive ingredients…
Stevie Gamble
Competing interests:
None declared
Competing interests: No competing interests
Editor,
On the one hand, Elwood et al. state that “Each person, not a doctor,
should evaluate the risks and benefits” whilst, on the other, that ”Health
promotion initiatives seem to achieve little behavioural change… health
education seems effective only in higher social classes.” [1] Not only
are these statements inconsistent, but the notion that the majority of
patients would be capable of weighing up the benefits and risks without
considerable guidance is fanciful.
Yet more problems arise on a closer examination of the argument used
by the authors to justify the use of aspirin in everyone over the age of
fifty years. This may be summarised as follows: more than half of all
individuals older than 50 years have a >3% five-year risk of a
cardiovascular event; adverse drug reactions due to low dose aspirin are
unusual and seldom serious; aspirin may have additional benefits including
reducing the risk of cancer and dementia; attempts to target high risk
groups have failed; therefore, all individuals over the age of 50 years
should be given aspirin.
This argument is, of course, flawed. Baigent, in the opposing
article, [2] provided ample reasons to dismiss the reliability of each of
the first three premises.
Indeed, Elwood et al. did themselves few favours by focusing on
epidemiological data that were more than 20 years old, by citing an
unconvincing paper in support of their claims about the side-effects of
aspirin, and by raising the issues of cancer and dementia, neither of
which are supported by robust data. However, even if all the premises are
accepted, they could not deliver the conclusion without any reference to
the benefits expected from aspirin therapy. There is, though, a ready
explanation for this ‘missing premise’. If Elwood et al. had specified a
risk reduction with aspirin, they would have had to relate this to the
type of patients studied; but, as soon as subgroups were introduced, the
evidence for the widespread use of aspirin would simply evaporate. No
wonder they remained silent on this matter.
To those who enthusiastically support the “polypill approach” to
medicine, the case made by Elwood et al. for the use of aspirin in all
patients over 50 years of age must be very disappointing. However, if this
is the best that can be done, then those who reject the medicalisation of
entire populations may breath a sigh of relief.
[1] Elwood P, Morgan G, Brown G, Pickering J. For and against:
Aspirin for everyone older than fifty? BMJ 2005;330;1440-1.
[2] Baigent C. For and against: Aspirin for everyone older than
fifty? BMJ 2005;330;1442-3.
Competing interests:
None declared
Competing interests: No competing interests
Herbalists may recommend intake of natural foods or herbs containing
saliclyate as a safer alternatives to aspirin.1 However, there is some
evidence of adverse effects of foods with a high salicylate content.
Feingold's hypothesis was that many hyperactive children are
hypersensitive to artificial colours and flavours and other chemical
additives and naturally occurring substances in foods. Feingold's additive
and salicylate-free Kaiser-Permenente diet for the treatment of
hyperactive children can be effective. An appropriate diet can reduce the
use of drug medications.2
Studies of irritable bowel syndrome identified adverse food reactions
to foods with a high salicylate or amine content when diarrhoea is
predominant.3 In a study of coeliac disease symptoms were especially
provoked by amine, salicylate and soy.4 Aromatic volatile ingredients in
food were found to elicit pseudoallergic reactions in chronic urticaria.
However, histamine, salicylate, and a direct mast-cell histamine release
were not found to be involved in this type of reactivity to naturally
occurring pseudoallergens.5
Reye's syndrome, a severe sepsis-like disease thought to be caused by
a hypersensitivity to salicylate in children with mild viral infections,
has virtually disappeared from much of the world after the use of
salicylate in febrile children was successfully discouraged.6
At what age does aspirin suddenly become safe to be used? How does
use in pregnancy affect the foetus? Is the child sensitised to salicylate
and more likely to become hyperactive?
The lack of safety of aspirin use in adults may be why there is no
overall mortality benefit in population trials.
1 McMullen MK. Are we medicating a nutritional deficiency?
http://bmj.com/cgi/eletters/330/7505/0-c#110006, 19 Jun 2005
2 Carter CM, Urbanowicz M, Hemley R, et al. Effects of few food diet
in attention deficit disorder. Arch Dis Child 1993: 69:564-8.
3 Niec AM, Frankum B, Talley NJ. Are adverse food reactions linked to
irritable bowel syndrome? Am J Gastroenterol. 1998; 93: 2184-90.
4 Faulkner-Hogg KB, Selby WS, Loblay RH. Dietary analysis in
symptomatic patients with coeliac disease on a gluten-free diet: the role
of trace amounts of gluten and non-gluten food intolerances. Scand J
Gastroenterol. 1999; 34: 784-9.
5 Zuberbier T, Pfrommer C, Specht K, et al. Aromatic components of
food as novel eliciting factors of pseudoallergic reactions in chronic
urticaria. J Allergy Clin Immunol. 2002 Feb;109(2):343-8.
6 Clark I, Whitten R, Molyneux M, Taylor T. Salicylates, nitric
oxide, malaria, and Reye's syndrome. Lancet. 2001; 357: 625-7.
Competing interests:
None declared
Competing interests: No competing interests
Dear Editor
Garlic may indeed be the answer [1] but we shouldn't fall into the
trap of thinking that it is entirely free from adverse effects because it
is a natural product.
The MHRA (as of January last year) had received 5 adverse reaction
reports of 11 reactions to Allium sativum. [2] Worryingly 3 of these
concerned suspected drug interactions. Many reports of adverse reactions
to garlic will also go unreported.
References
1. Gibbon NK. Garlic may be the answer. Available at
http://bmj.bmjjournals.com/cgi/eletters?lookup=by_date&days=1#110159
(Accessed 23/6/05)
2. MHRA. Adverse drug reactions online information tracking - Drug
analysis print. Available at
http://www.yellowcard.gov.uk/dapdocs/allium_sativum.pdf (Accessed 23/6/05)
Competing interests:
None declared
Competing interests: No competing interests
Recommending aspirin for everyone over 50 has overlooked a dose that
looks at the ratio of benefit to risk, considering an individual still has
at least a third of life span remaining, and older hypertensives are
susceptible to haemorrhagic stroke. The debate of how low is low has gone
on long enough with no definite answer beyond 75mg to over 4 times its
multiple at 325mg for secondary prevention of cardio and cerebrovascular
thrombotic disease.
Aspirin across the board for primary prevention may be considered in
patients with a 10% risk of coronary heart disease and demands looking at
the risk-benefit balance between the number of myocardial infarctions that
can be prevented versus the risk of hemorrhagic stroke and gastro-
intestinal bleeds.
Bandolier has looked at randomnised controlled trials in patients at
low risk of CVD and failed to find sufficient evidence of benefit (1). A
metanalysis of subjects at moderate risk indicates the risk of thrombotic
stroke is overemphasised and overpowers the risk of major bleeds even from
low dose aspirin (2).
Cost is often a limiting factor in Trinidad and Tobago where enteric-
coated or slow release preparations are not available in the public sector
and not many patients can afford these preparations which may reduce the
incidence of gastrointestinal blood loss. Patients must take
responsibility for their health, but if they are also expected to make
their choice of therapy, why need a physician at all?
The evidence of benefit of using aspirin as primary prevention to
influence cardiovascular outcomes is still awaited and till it is
generated: avoid the possible harm.
1.http://www.jr2.ox.ac.uk/bandolier/band105/b105-5.html
2.Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of
randomised trials of antiplatelet therapy for prevention of death,
myocardial infarction, and stroke in high risk patients. BMJ 2002;324: 71-
86
Competing interests:
None declared
Competing interests: No competing interests
I am surprised that this article, which only elaborates what is
already known,finds a place in BMJ.
This should have been more expressive some more research should have
gone into it.References to data and research over the last 30 years
alongwith the benefits or otherwise over the years should have been added
to it.What it adds as benefits (reduced risk of cancer and dementia)are
also not proven.
This could have been published 30 years ago and nobody would have
been able to tell the difference.
Competing interests:
None declared
Competing interests: No competing interests
Instead of worrying over the side- effects of aspirin,why do we not
promote garlic which has similar anti-platelet properties and many more
vascular advantages as well without the risk of adverse reactions?(There
is plenty of evidence for this in the literature which includes double-
blind clinical trials using aged garlic which is odourless).
Eight years ago, I had a quadruple coronary bypass operation. I
refused to take aspirin post-operatively as I have a bad history of peptic
ulcer. Clopidogral resulted in several haemoptyses and,having researched
the literature (very carefully!) I opted for Kyolic Aged Garlic, mg 600
b.d. Now aged 86,I have had no reason to regret this decision.
Competing interests:
None declared
Competing interests: No competing interests
I am quite surprised that the authors have wily nily let the
profession off the hook vis-a-vis the risks of aspirin prophylaxis for
myocardial infarction. To leave the onus of decision taking on the
patient, instead of being an informed mentor in the fight against vascular
disease, is in my view, alarming.
How can (I quote from the article),'each person, not a doctor, should
evaluate the risks and benefits' be of much value to decison making in a
patient unaware of drugs and pharmacotherapeutics?
In the same article later,the authors advice that,'they (the patients) are
likely to accept a small increased risk of bleed or other side effect in
exchange for a reduced risk of a heart attack or stroke' is if anything,an
indirectly offered 'medical advice' from doctors.
Passing the buck is impossible when the buck stops here, in the
consultating room
Competing interests:
None declared
Competing interests: No competing interests
It is surprising that neither author involved in the debate for and
against the prescribing of aspirin for those over 50 mentions the growing
notion of aspirin resistance. This term is used to describe not only an
absence of the expected pharmacologic effects of aspirin on platelets, but
also poorer than expected clinical outcomes. Thus there are two
definitions of this condition - biochemical aspirin resistance, in which
the in vitro activation of platelets is persistent or clinical aspirin
resistance where there are recurrent vascular events in individuals
already on aspirin.
Several authors have now documented that a substantial minority of
individuals may have either total or partial aspirin resistance. These
studies have been summarised elsewhere (1). Whilst these studies may have
methodological differences, they suggest that between 5% and 55% of
treated individuals may have some degree of aspirin resistance. Recent
data suggests that even in individuals who are at potentially greater risk
of cardiovascular events than a normal population, a substantial
proportion have insulin resistance (2).
An increased level of complexity with this argument is that it has
yet to been shown whether aspirin related side effects are less common in
aspirin resistant individuals. If they are not, then universal aspirin
administration may be associated with an increase in side effects with no
concurrent decrease in cardiovascular events.
Until these issues have been further investigated, it seems unwise to
recommend aspirin for everyone over 50 years old.
(1) Sanderson S, Emery J, Baglin T, Kinmouth A. Aspirin resistance
and its clinical implications. Ann.Intern.Med. 2005;142:370-80.
(2) Fateh-Moghadam S, Plöckinger U, Htun P, Reuter T, Ersel S, Gawaz M et
al. Prevalence of aspirin resistance in patients with type 2 diabetes.
Acta Diabetol. 2005;42:99-103.
Competing interests:
None declared
Competing interests: No competing interests
Sins of commission and omission
I believe that there is an important difference between causing harm
by commiting an act (in this case, prescribing aspirin)and by failing to
do so (not prescribing). To put it another way, the person who is
persuaded, or chooses, to take aspirin for the theoretical benefit of
prevention of stroke or cardiac event, but who then goes on to suffer a
serious haemorrhagic event is quite rightly going to blame the aspirin and
the prescriber(or themselves, if they have made the decision without
medical advice). If, however, they choose not to take aspirin but go on
to have a thrombolic event, there is much less cause to attribute this to
failure to prescribe aspirin, which after all only reduces the relative
risk and does not abolish it altogether. Last year an elderly patient of
mine suffered a major G-I bleed while on aspirin (she had controlled
hypertension); a fortnight later, after the aspirin had been stopped, she
died of a stroke. I feel much more responsible for the first event than
the second. I'm not sure if this is rational, but I think most people
would feel the same.
Competing interests:
None declared
Competing interests: No competing interests