Aspirin Alone for the Prevention of Atherothrombotic Events. N Engl Download full-text
J Med 2006;354:1706-17.
22. Frelinger AL III, Furman MI, Linden MD, Li Y, Fox ML, Barnar MR,
et al. Residual arachidonic acid-induced platelet activation via an
cyclooxygenase-2-independant pathway. A 700-patient study of
aspirin resistance. Circulation 2006;113:2888-96.
Submitted Dec 14, 2006; accepted Jan 24, 2007.
Thomas G. Lynch, MD and Iraklis I. Pipinos, MD, Omaha, Neb
The authors’ manuscript reflects an area of growing interest in
other specialties and should serve to stimulate research opportuni-
ties in vascular surgery. Articles relating to aspirin resistance have
been published in the stroke and cardiology literature, where an
increasing number of studies have shown an association between
the incidence of adverse thrombotic events and aspirin resistance.
The subject, however, has not been widely addressed in the vascu-
While important, the manuscript must be taken in context. As
noted by the authors, aspirin resistance is not yet clearly defined,
and can be characterized by laboratory measures or adverse clinical
events. Laboratory measures of platelet function can include in
vivo testing, such as bleeding time. Ex vivo tests include the
measurement of arachidonic acid metabolites, such as urinary
11-dehydro TXB2; measures of platelet-platelet interaction, such
as optical or impedance aggregometry; point of care cartridge
based analyzers, such as the PFA-100; and whole blood flow
cytometry, which measures activation dependent changes on the
platelet surface (such as CD62p, p-selectin; activated GPIIb/IIIa;
leukocyte platelet aggregates), activation dependent signaling, and
activation dependent release from platelets. Of concern, however,
the reported incidence of aspirin resistance is variable, even using
etry has ranged from 0.4% to 9%, and using the PFA-100 from 9%
Clinical studies have demonstrated a higher incidence of aspi-
rin resistance among patients with a prior history of transient
ischemic attack or stroke; high risk patients with a history of
coronary artery disease have increased odds of being aspirin resis-
tant.2 Mueller et al.3 followed 100 patients with intermittent
after balloon angioplasty. Only 40% of male patients showed the
expected effect of aspirin using in vitro platelet aggregation. All
reocclusions at the site of angioplasty occurred in this group.
Higher vascular event rates have also been correlated with mea-
etry, urinary 11-dehydro TXB2levels, and the PFA-100 have been
used to assess platelet function. Interestingly, results from the
PFA-100 did not correlate with aggregometry and did not corre-
late with vascular events.1
The current study uses two techniques to assess laboratory
evidence of aspirin resistance in patients on chronic aspirin therapy
and illustrates the caution that must be exercised in interpreting
results. Measurement of arachidonic acid induced expression of
CD62p (P-selectin), using flow cytometry, demonstrates that all
patients receiving aspirin show an aspirin effect, while PFA-100
closure times indicate 16% of patients taking aspirin show no effect
of aspirin. The PFA-100 can be influenced by multiple variables,
including platelet count, platelet function, red blood cells, and von
Willebrand factor; and the outcome can be effected by variables,
such as von Willebrand factor, that are not influenced by aspirin.
None-the-less, the current study is a very nice introduction to the
concept of aspirin resistance and provides an example of its appli-
cation in vascular surgery. While the study demonstrates evidence
of laboratory resistance, it has failed to exclude patient noncom-
resistance with clinical evidence of adverse events. The study also
demonstrates that laboratory measures can influence the extent
randomize aspirin therapy and laboratory adjusted aspirin therapy,
based on identified resistance; verification of compliance and doc-
umentation of clinical outcomes should be incorporated.
1. Dalen JE. Aspirin resistance: Is it real? Is it clinically significant? Am J
2. Mason PJ, Jacobs AK, Freedman JE. Aspirin resistance and atherothrom-
botic disease. J Am Coll Cardiol 2005;46:986-93.
3. Mueller MR, Salat A, Stangl P, Murabito M, Pulaki S, Boehm D, et
al.Variable platelet response to low-dose ASA and the risk of limb
deterioration in patients submitted to peripheral arterial angioplasty.
Thromb Haemost 1997;78:1003-7.
JOURNAL OF VASCULAR SURGERY
Volume 45, Number 6
Lynch and Pipinos 1147