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.