Suboptimal Antiplatelet Therapy Suggested By Platelet Aggregation Studies Does Not Correlate with a Change in Clinical Management
Authors: Gopalakrishnan Dharmesh , Rogers Heesun J , Elson Paul , McCrae Keith R. 
Published: October 2019

Abstract
Introduction: With the expanding repertoire of antiplatelet drug targets and therapies, quantifiable parameters to assess their efficacy can prove to be useful in clinical decision-making. In this retrospective analysis we examined patients who had platelet aggregation testing done at our center between August 2008 and August 2013, focusing on those who were on some form of antiplatelet therapy during testing. Our goal was to define the impact of platelet aggregation testing on decision-making regarding continuation or change in antiplatelet therapy.
Methods: Light transmission aggregometry (LTA) was used to assess efficacy of treatment with antiplatelet agents. Inhibition of platelet aggregation in response to ADP and arachidonic acid are reflective of the therapeutic effect of aspirin, while inhibition of platelet aggregation in response to ADP reflects the effect of P2Y12 receptor antagonists. As per parameters developed at our center, the combination of arachidonic acid aggregation <20 percent and ADP aggregation (at concentration of 5 uM) <70 percent is indicative of optimal therapeutic response to aspirin. Though not fully standardized, ADP aggregation < 40% is considered to be indicative of therapeutic response to clopidogrel. Descriptive statistics for frequency were used. Pearson coefficient was used to assess correlation.
Results: We studied results of platelet aggregometry in 117 patients who were on some form of antiplatelet therapy - 81 on a single agent (72 on aspirin alone, 9 receiving P2Y12 antagonist alone), 34 on dual therapy (33 on aspirin + P2Y12 antagonist, 1 on aspirin + cilostazol), and 2 patients on triple therapy (1 on aspirin + P2Y12 antagonist + cilostazol, 1 on aspirin + dipyridamole + cilostazol). None of our patients were on Gp IIb/IIIa inhibitors. In total, 108 patients were on aspirin therapy and 43 patients were on P2Y12 inhibitors. In 65 out of these 117 patients, the primary indication for platelet aggregation testing was to monitor the efficacy of antiplatelet therapy, while in the remaining 52, testing was done for other indications. Fifty-nine of these 65 patients were tested in the setting of a recent thrombotic event in the cerebral, coronary, peripheral, or other vascular bed. While 68 (58%) patients had optimal therapeutic response, 49 (42%) patients - 38 of the 108 (35%) patients on aspirin, and 14 of the 43 (32%) patients on a P2Y12 inhibitor - had evidence of suboptimal response to the respective agent. However, antiplatelet therapy was changed or adjusted in only 8 of these 49 patients following these sub-optimal test results, and only 3 had repeat testing following the change (all three of whom were shown to have complete response). Among the 108 patients on aspirin therapy, the total daily dose did not correlate either with the PFA-100 closure times (Collagen/ADP or Collagen/epinephrine) or with the degree of platelet aggregation in response to any of the agonists (ADP, arachidonic acid, collagen, epinephrine or ristocetin).
Conclusions: Most of the patients who underwent platelet aggregation testing to monitor the efficacy of antiplatelet therapy had a recent thrombotic event that prompted the test. Though 42% of patients on antiplatelet agent(s) had in vitro evidence of sub-optimal platelet inhibition, antiplatelet therapy was changed or adjusted in only 16% of these individuals, and only 6% had repeat testing following the change. This suggests that, though platelet aggregation testing was potentially useful in monitoring efficacy of platelet inhibition, clinical changes in antiplatelet therapy were guided more by other factors, casting uncertainty upon the cost effectiveness of platelet function testing in this population. No significant increment was found in the in vitro antiplatelet effect of aspirin with increasing daily doses, suggesting lack of a dose-response beyond 81 mg per day.

Disclosures
McCrae: Syntimmune: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees; Halozyme: Membership on an entity's Board of Directors or advisory committees; Momenta: Consultancy.