4. DISCUSSION
A true resistance to inhibition of thromboxane A2, i.e. the resistance
to the biochemical effects of aspirin is rare. On the other hand,
thrombotic events and poor clinical outcomes despite the use of aspirin
in patients could secondary to multiple mechanisms, but not limited to
the inhibition of the COX-1 enzyme.32 Hence, the term
“anitplatelet resistance” is not uniformly defined in the literature.
However, antiplatelet resistance demonstrated with in-vitro platelet
assays has been linked to adverse clinical outcomes in patients on
antiplatelet therapy.33–36
Studies reporting the antiplatelet resistance in cardiac surgery
patients have different cut-off values for measurement; even when they
used the same assessment method, let alone different measurement
methods. For example, using light aggregometry, aspirin resistance is
determined at platelet aggregation ≥20% in one
study13 but defined as >30% in other
studies.26,27
Different assessment methods also mean different results in assessing
antiplatelet resistance, making it non-interchangeable between
studies.11 A patient deemed antiplatelet resistant in
one study may not be equivalent to being antiplatelet resistant in
another study using a different assessment method. In addition,
different doses of aspirin used in individual studies might have had an
impact on aspirin resistance.
Furthermore, studies assessing antiplatelet resistance focused heavily
on the assessment of aspirin resistance, but scanty information is
available on the resistance of other antiplatelets, such as clopidogrel.
Most of the assessment methods offer the ability to test clopidogrel
resistance using ADP instead of arachidonic acid as a substrate, yet it
is not widely employed. Despite clopidogrel being used in many
studies15,16,23,24,28, only one study examined and
reported clopidogrel resistance.23
Previous studies in the non-cardiac surgery cohort demonstrated that
antiplatelet resistance is associated with higher rates of
cardiovascular thrombotic events and
mortality.35,37,38 Although there are a few randomised
controlled trials and observational studies which reported no
significant difference in adverse outcomes in patients undergoing
cardiac surgery, including mortality, stroke and myocardial infarction,
they did not investigate graft patency or patient
symptoms.20,21,28 No difference in adverse outcomes
may be because aspirin resistance could be transient in
nature.13,26,27 Aspirin resistance is associated with
less blood loss in the immediate postoperative
period,29 which could be loosely translated into a
pro-thrombotic feature when compared with the aspirin-sensitive
population.
The clinical outcomes were improved in a subset of younger
(<65 years) and obese patients with aspirin resistance when
dual antiplatelet therapy with clopidogrel is used.28Besides, all patients who died during the follow-up period were found to
have perioperative aspirin resistance initially.26,27Youn et al reported worse outcomes in patients undergoing cardiac
surgery with clopidogrel resistance.24 Assessment of
this patient cohort could be improved by using follow-up coronary
angiogram and/or computed tomography coronary angiography.
This systematic review is not without limitations. Most of the studies
included are observational cohort studies rather than randomised
controlled trials. Due to the applications of various assessment methods
for antiplatelet resistance and their diverse results, it is not
possible to carry out a meta-analysis. There is also a lack of
uniformity in the definition of Antiplatelet resistance using different
methods. Future research should aim to generate adequately powered
randomised controlled trials to demonstrate standardised results of
antiplatelet resistance, single agent or in combinations, including the
resistance of other antiplatelet agents, rather than being limited to
aspirin. The clinical relevance of resistance to antiplatelet medication
requires more imaging investigation by taking into consideration the
quality of the grafted coronary artery.