Академический Документы
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S756
DOSING
Considerable progress has been made
toward optimal dosing of aspirin, as an
outgrowth of many recent trials. Although
the trials have not randomly assessed the
dose of aspirin, the striking feature has
been the established framework for a
bleeding hazard gradient as the dose is
increased from 75 mg to 325 mg daily. In
the past, this entire range was considered
low dose, but the Blockade of the
Glycoprotein IIb/IIIa Receptor to Avoid
Vascular Occlusion (BRAVO) and
Clopidogrel in Unstable Angina to
Prevent Recurrent Events (CURE) trials
and a large meta-analysis show at least a
doubling of major bleeding with higher
aspirin doses (>150 mg) compared with
the 75-mg to 81-mg doses.11-13 Most of the
bleeding excess is related to gastrointestinal hemorrhage. In combination with
clopidogrel, higher-dose aspirin (>81 mg)
results in a significantly increased bleeding hazard.
There have been no convincing data to
show a dropoff of efficacy in this dose
range. In the ATC analysis, the proportionate benefit in the 12 trials testing 75
mg to 150 mg of aspirin was at least as
high as any other dose category (53 trials).6 The only large-scale randomized trial
assessing aspirin dose was the Dutch
Transient Ischemic Attack trial, which
showed no reduction of efficacy for
aspirin dosing of 30 mg compared with
283 mg.14 The results of the BRAVO trial
raised the possibility that the higher dose
of aspirin (>150 mg) would be associated
with less mortality, but this was not a randomized trial, and these results have not
been replicated by similar analyses from
parallel projects.11
RESISTANCE AND
DRUG-DRUG INTERACTIONS
There are some important issues that
have emerged with respect to aspirin resistance and interactions with other medications. Aspirin resistance, defined by
persistent platelet aggregation to multiple
agonists, has been documented in a limited proportion of patients, and it remains
unclear whether higher doses of aspirin
Vol. 3 (8B)
August 2003
CVD PREVENTION
S757