Over the couple of
years, low dose aspirin (a nonsteroidal antiinflammatory
drug, NSAID) has been one of the most important drugs
for the treatment and prevention of cardiovascular
disease (CVD) including heart attack, stroke and
peripheral artery disease (poor circulation) in the
legs. Several large trials, primarily among men, have
demonstrated that aspirin prevents first heart attack in
people who have no signs or symptoms of cardiovascular
disease. It is often a life-saver for those with history
of heart attack, stable or unstable angina, coronary
bypass graft surgery or percutaneous coronary
intervention (angio-plasty) [1].
Even at low doses,
aspirin has analgesic (relieve minor aches and pains),
antipyretic (reduce fever) and anti-inflammatory
effects. It
also has an
antiplatelet effect by
inhibiting the production of
thromboxane, which
under normal circumstances binds
platelet molecules
together to create a patch over damage of the walls
within blood vessels. It thus
prevents the narrowing of arteries in coronary heart
disease as a blockage that is of longer duration can
result in a heart attack (myocardial infarction) [2].
Aspirin uncouples
oxidative phosphorylation
in cartilaginous (and hepatic) mitochondria, by
diffusing from the inner membrane space as a proton
carrier back into the mitochondrial matrix, where it
ionizes to release protons [3]. At high doses, it may
actually cause fever owing to the heat released from the
electron transport chain, as opposed to it antipyretic
action seen with lower doses. Aspirin is also known to
induce the formation of nitric oxide-radicals in the
body, which can reduce inflammation [4]. There is
evidence to suggest that salicylate and its derivatives
modulate signaling through
NF-κB (a
transcription factor
complex that plays a central role in many biological
processes including inflammation) [5].
Particularly at high doses, aspirin is known to be
associated with some undesirable effects especially
gastrointestinal
ulcers, stomach
bleeding, and
tinnitus. The
implication of the drug in
Reye's syndrome has
been the major reason why it is no longer recommended in
children and adolescents to control
flu-like symptoms or
the symptoms of
chickenpox or other
viral illnesses.
Although
the optimum dose of aspirin for preventing
cardiovascular disease events is unknown, primary
prevention trials have demonstrated benefits with
various regimens, including dosages of 75 and 100 mg per
day and 100 and 325 mg every other day. It does appear
that a dosage of approximately 75 mg per day appears is
as effective as higher dosages which often exposes
patients to higher risks of gastrointestinal bleeding
[6]. Recently, the potential harm of an increase in
gastrointestinal hemorrhage from low dose aspirin has
become a primary issue. Also, there
has been controversy as to whether it should be used in
patients with
chronic heart failure (CHF). While it
can prevent reinfarction in many patients with
underlying coronary disease, the benefit lessens after
the first 6 to 12 months after infarction and there is
evidence that in some cases, it may also worsen the
outcomes in CHF patients, possibly because it inhibits
prostaglandins, with resulting adverse hemodynamic and
renal effects [6].
While
aspirin will continue to be useful in managing some
cardiovascular diseases, the potential harm is
recommended to be weighed against the potential benefits
before it is recommended for any person. Men aged 45 to
79 years are encouraged to use aspirin when the
potential benefit of reduction in myocardial infarctions
outweighs the potential harm of an increase in
gastrointestinal bleeding. On the other hand,
women aged 55 to 79 years are encouraged to use it when
the potential benefit of reduction in ischemic strokes
outweighs the potential harm of an increase in
gastrointestinal hemorrhage. The use of aspirin in men
and women younger than 45 and 55 years, respectively is
not encouraged [7]. Although the incidence of
myocardial infarction and stroke is high in persons 80
years or older, and thus the potential benefit of
aspirin is large, there is no sufficient evidence to
encourage or discourage the use in this age group [7,8].
References
