|
We do not know who
should be given what dose and for how long
As a result of the findings of the aspirin
study discussed in another newsletter article this week (An
Aspirin a Day May Not Keep the Doctor Away) and editorial
appeared in the same issue of the British Medical Journal
(BMJ), with the same title and subtitle as above. Dr. Martin
R Tramèr of Geneva University Hospital in Switzerland
discusses the issue of aspirin use at some length, even including
some historical facts, such as:
- The active ingredient in aspirin (salicylic acid)
has been used to relieve pain and fever as far back as 2,000 years ago
by the Greeks.
- At the end of the 19th century acetyl salicylic
acid (aspirin) started being produced on an industrial scale and aspirin
soon became a widely used painkiller.
- In the late 1960s it was found that a single
dose of aspirin irreversibly inhibits the normal aggregation of platelets
by suppressing the production of a substance known as thromboxane A2.
This effect of aspirin persists until newly formed platelets have been
released. The biological lifespan of a platelet is about nine days.
Thromboxanes are a group of substances known as
eicosanoids that are produced from arachidonic acid by the action of an
enzyme known as cyclooxygenase. Thromboxane A2 is powerful aggregator
of platelets and also a vasoconstrictor.
Dr. Tramèr notes that this "blood
thinning" or antithrombotic effect of aspirin is actually an adverse
reaction of the drug.
He notes that beginning with a 1991 report in the
Archives of Internal Medicine, it has been suggested that aspirin should
be given to all men aged 50 years or older and to all women after the
menopause. However, Dr. Tramèr notes two reasons
why this "enthusiasm needs to be dampened":
Firstly, aspirin, through its ability to block
the synthesis of prostaglandins, may damage the gastrointestinal mucosa.
Erosions may be trivial, but they may progress to ulcers, which in turn
may bleed or perforate, and may even
kill. This happens more often than many doctors like to believe.
Secondly, reduced thrombus formation results
in a greater tendency to bleed. Thus, in a patient who is taking aspirin
any ulcer that may arise may bleed even more extensively.
In light of these potential dangers, therefore,
many physicians have logically aimed to use the minimum dose of aspirin
that inhibits thrombus formation, on the assumption that this would also
minimize the risk of gastrointestinal complications. This is the rationale
behind the use of daily low dose aspirin to prevent heart disease.
However, Dr. Tramèr notes that the latest
systemic review published by the BMJ provides strong evidence that
these previous assumptions may have been incorrect. He notes that the
study found "no evidence of dose responsiveness over a wide range
of doses (50 to 1500 mg/day)."
Dr. Tramèr notes that in the physician's
health study, a large randomised trial of 11,037 patients given aspirin
325 mg every other day for 60 months, as many as 3.6%
had symptoms of hematemesis (the vomiting of blood) or melena (blood in
the stools).
Referring to the current study, Dr. Tramèr
states that "the most important message in Derry and Loke's paper
is that there is no gain without pain."
Unfortunately, the study leaves more questions than
answers, such as "Who should be given what dose of aspirin, and for
how long?" to which he tries to shed some light:
- "In patients with a history of stroke or
transient ischemic attack, the minimal effective dose of aspirin to
prevent further vascular accidents remains unknown."
- "Nor do we know how long patients have to
take aspirin."
- "In the prevention of recurrent stroke aspirin
seems to be of benefit independent of the patient's age."
- "However, in elderly patients with atrial
fibrillation the benefit of prophylactic aspirin to prevent strokes
is unproved."
- "Also the risk of both gastrointestinal
complications and perhaps congestive heart failure with non-steroidal
anti-inflammatory drugs may increase with increasing age."
In the light of the results from the current study, "it
may be more appropriate for some people to eat an apple rather than an aspirin
a day," notes Dr. Tramèr.
British Medical
Journal November 11, 2000; 321: 1170-1171
|