Sex-Related Differences in On-Treatment Platelet Reactivity in Patients with Acute Coronary Syndrome

<b>Background:</b> Dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor is recommended for patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI). On-treatment platelet reactivity has been associated with ischemic endpoints and may vary between male and female patients. We, therefore, investigated sex-related differences in on-treatment platelet reactivity in ACS patients receiving ticagrelor or prasugrel. <b>Methods:</b> Maximal platelet aggregation by light-transmission aggregometry (LTA) and platelet surface P-selectin expression in response to arachidonic acid (AA), ADP, collagen, TRAP (a protease-activated receptor [PAR-1] agonist), and AYPGKF (a PAR-4 agonist) were assessed in 80 prasugrel- and 77 ticagrelor-treated patients 3 days after PCI. <b>Results:</b> In the overall study population (n = 157), women were older and had lower serum creatinine, hemoglobin, and hematocrit levels than men (all <i>p</i> < 0.05). Women exhibited higher ADP-inducible platelet aggregation in response to both 10 μM and 5 μM of ADP (both <i>p</i> < 0.05), while no sex-related differences were observed for AA-, TRAP-, collagen-, or AYPGKF-inducible platelet aggregation and agonist-inducible platelet surface P-selectin expression. In prasugrel-treated patients, women had higher ADP-inducible platelet aggregation and P-selectin expression compared with men (both <i>p</i> < 0.05), whereas no sex-related differences were found in ticagrelor-treated patients. In the multivariate linear regression analyses, female sex remained an independent predictor of higher platelet aggregation in response to 5 μM of ADP in prasugrel-treated patients (<i>p</i> < 0.05). High on-treatment residual platelet reactivity (HRPR) in response to AA was detected in four patients, and HRPR ADP was seen in seven patients, with no significant differences between female and male ACS patients (both <i>p</i> > 0.05). Low on-treatment residual platelet reactivity (LRPR) in response to AA was identified in 153 patients and LRPR ADP was present in 80 patients, with a higher prevalence of LRPR ADP in men (<i>p</i> = 0.01). <b>Conclusions:</b> Female ACS patients on prasugrel exhibited higher ADP-inducible platelet aggregation than male patients, while no sex-related differences were observed in patients on ticagrelor.