Abstract 17453: In vitro Aspirin Responsiveness Can Predict Platelet Hyperreactivity and Cardiovascular Risk

Abstract

Background: While antiplatelet therapy decreases cardiovascular events, insufficient platelet aggregation suppression by antiplatelet therapy is associated with an increased risk of cardiovascular events. In this study, we developed a diagnostic tool to establish an individual’s “aspirin (ASA) responsiveness” in vitro and investigated its association with other metrics of platelet activity and cardiovascular risk. Methods: In 115 subjects off all antiplatelet therapy, platelet aggregation in response to high-dose of arachidonic acid (AA; 1.5 mM) with and without incubation of platelet-rich plasma with ASA (3 mM) was measured by light transmission aggregometry (LTA). ASA responsiveness was defined as ([% aggregation to AA - % aggregation to AA + ASA] / % aggregation to AA) x 100. Next, we correlated ASA responsiveness with other metrics of platelet activity. Finally, we evaluated its clinical significance in a cohort of patients undergoing lower extremity revascularization (LER) followed longitudinally for cardiovascular events. Results: Among 115 participants (mean age 50.3 years old, 65% female, and 43.5% underrepresented minorities, off all antiplatelet therapy), mean % aggregation to high-dose AA was 89.5% ± 3.5. In vitro ASA responsiveness was variable, mean 73.72% ± 15 (range: 13.7% to 97.6%). ASA responsiveness was lower in older (P<0.05) and female participants (P<0.05) and was not associated with race/ethnicity, diabetes, or platelet count. Lower ASA responsiveness was associated with a significant increase in platelet aggregation to epinephrine (0.4 μM, P=0.0004), ADP (1.0 μM, P=8.89x10 -9 ), and collagen (0.2 μg/mL, P=1.16x10 -9 ). In an independent cohort of 67 patients undergoing LER, lower in vitro ASA responsiveness (e.g. a reduced platelet-inhibiting effect), was associated with a significantly increased risk of major adverse cardiac and limb events (1 st tertile-63.6%, 2 nd tertile-50.0% and 3 rd tertile-27.3%; P=0.016 for trend). Conclusions: Reduced ASA responsiveness is associated with increased platelet activity and a higher risk of cardiovascular events. We propose that this rapid, relatively simple assay may be used preclinically for ASA testing and to identify individuals at high cardiovascular risk.