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Additional Topics: Large Randomized Clinical Trials
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Low-Dose
Aspirin Inhibits Arachidonic Acid-Precipitated
Platelet Aggregation, but not Collagen-Precipitated
Platelet Aggregation.
Roehm E.,
Am J Cardio 1995; 76:637-638. The
article by Dabaghi et al documents the effect of varying doses of aspirin
on platelet aggregation in response
to arachidonic acid. Whether small, single doses of aspirin are effective
in adequately inhibiting platelet
aggregation is an important clinical consideration. When aspirin is given
as a single, acute dose before emergency coronary angioplasty, it is
important to give a dose that is adequate
to provide the full effect of aspirin inhibition on platelet aggregation.
A prior randomized study has
documented a fourfold reduction in
myocardial infarction with high dose
aspirin (330 mg administered 3 times daily) in patients undergoing routine
percutaneous transluminal coronary angioplasty. Dabaghi
et all document that platelet
aggregation is fully inhibited
by a single dose of aspirin when arachidonic acid is used as the stimulating agent, regardless of whether
81,
162, or 324 mg is given. They also document
that low doses of aspirin effectively inhibit thromboxane B2 metabolism. These results are However, when viewed in
the context of
previously published reports, Dabaghi et all do not show that an 80 mg dose of aspirin gives
the
full potential effect of aspirin inhibition
on platelet aggregation when other agents are used to induce platelet aggregation. Collagen is a potent
stimulus
of platelet aggregation. Kuster
and Frolich3 showed that 24 hours after the ingestion of
100 mg of aspirin, less than half of
aspirin's inhibitory effect on
platelet aggregation is achieved
when compared with a 500 mg single,
acute dose of aspirin. The only other
investigators looking at the acute
effects of low-dose aspirin with collagen
stimulation were Paccioretti and
Block.4 However,
this study did not have adequate numbers
for any definitive evaluation. The
dose of 81 mg was studied in 7
subjects, and 162 mg was studied in 3
subjects when a collagen stimulus was
used. Four of the total 10 tests,
using either 81 or 162 mg of aspirin,
showed no inhibition of platelet
aggregation using a collagen stimulus
in the study by Paccioretti and Block.
This is equal to a total of 4 of 4
tests showing platelet aggregation inhibition when >200 mg of There
is an additional study by Mehta
et al5 on the acute effects of a
single dose of aspirin, which compares
the effect of different doses of aspirin
on platelet aggregation; this was incorrectly represented in the study by Dabaghi et al.' Mehta et al
showed
that 40 mg of aspirin produced
a modest decrease in platelet aggregation
with epinephrine stimulation at 1 hour. Mehta et al state that "the magnitude of the inhibition of platelet
aggregation by 325 mg and 650 mg doses was similar." However, they did not say that the 40 mg
dosage
of aspirin had the same effect on
platelet aggregation as
higher doses of
aspirin. Their data suggest a
difference in the extent of platelet aggregation with an epinephrine stimulus
when a 40 mg dose is compared
with either a 325 or 650 mg aspirin
dose. Thus,
a review of the study by Dabaghi
et all and of previous studies gives the following information: Thromboxane metabolism is inhibited
by a single, low dose of aspirin. Low
dose
aspirin in the 80 to 100 mg range gives the full inhibitory effect on platelet aggregation possible when
arachidonic
acid is used as a platelet aggregation stimulus. Kuster and Frolich,3
in an outstanding study in which
the effect of a collagen stimulus
on platelet aggregation was evaluated,
showed that a greater degree of inhibition of platelet aggregation
was achieved with a single 500
mg dose of aspirin compared with
a single 100 mg dose of aspirin. As noted by Dabaghi et al,' the clinical setting provoking interest in the acute effects of a single dose of aspirin results from patients with an acute ischemic syndrome undergoing either acute angioplasty or receiving thrombolytic therapy. Because there is a strong stimulus to thrombosis in these clinical settings, it is important to consider more intense potentiators of platelet aggregation such as collagen and epinephrine, in addition to the more easily inhibited arachidonic acid precipitated platelet aggregation. A ruptured plaque has the potential for adenosine phosphate, collagen, and epinephrine-induced platelet aggregation. Hence, though aspirin can achieve only partial inhibition of collagen-precipitated platelet aggregation, it is clinically relevant that a single low dose of aspirin achieves less inhibition of platelet aggregation than a higher dose of aspirin. The therapeutic goal of the cardiologist caring for a patient with a disrupted atherosclerotic plaque in the setting of an acute ischemic syndrome, is to achieve the fullest platelet inhibition possible with aspirin (and not to achieve selective inhibition of arachidonic acid induced platelet aggregation) . |