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Sex-Related Differences in On-Treatment Platelet Reactivity in Patients with Acute Coronary Syndrome
David Mutschlechner1,2,3, Anastasios Tsarouchas1, Maximilian Tscharre4,5,6
1Department of Internal Medicine I, Cardiology and Intensive Care Medicine, Landesklinikum Mistelbach-Gänserndorf, 2130 Mistelbach, Austria.
Insights
Female patients with acute coronary syndrome (ACS) on prasugrel showed higher ADP-induced platelet aggregation than males. No significant sex differences in platelet reactivity were found in ACS patients treated with ticagrelor.
Area of Science:
- Cardiology
- Pharmacology
- Hematology
Background:
- Dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor is standard for acute coronary syndrome (ACS) patients post-percutaneous coronary intervention (PCI).
- On-treatment platelet reactivity is linked to ischemic events and may differ between sexes.
- This study examined sex-based variations in platelet reactivity among ACS patients on ticagrelor or prasugrel.
Purpose of the Study:
- To investigate sex-related differences in on-treatment platelet reactivity.
- To compare ADP-inducible platelet aggregation and P-selectin expression between male and female ACS patients.
- To determine if these differences are drug-specific (ticagrelor vs. prasugrel).
Main Methods:
- Assessed maximal platelet aggregation using light-transmission aggregometry (LTA).
- Measured platelet surface P-selectin expression in response to various agonists (ADP, AA, collagen, TRAP, AYPGKF).
- Analyzed data from 157 ACS patients (80 prasugrel, 77 ticagrelor) 3 days post-PCI.
Main Results:
- Women were older with lower creatinine, hemoglobin, and hematocrit than men.
- Women exhibited higher ADP-inducible platelet aggregation (10 μM and 5 μM ADP) than men.
- In prasugrel users, women showed higher ADP-induced aggregation and P-selectin expression; no sex differences were seen with ticagrelor.
- Female sex independently predicted higher ADP-induced aggregation in prasugrel-treated patients.
- No significant sex differences in high on-treatment residual platelet reactivity (HRPR) for AA or ADP.
- Men had a higher prevalence of low on-treatment residual platelet reactivity (LRPR) for ADP.
Conclusions:
- Female ACS patients treated with prasugrel demonstrate increased ADP-inducible platelet aggregation compared to males.
- No significant sex-based differences in platelet reactivity were observed in ACS patients treated with ticagrelor.
- These findings suggest drug-specific sex differences in P2Y12 inhibitor efficacy.
Abstract:
Background: 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. Methods: 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. Results: In the overall study population (n = 157), women were older and had lower serum creatinine, hemoglobin, and hematocrit levels than men (all p < 0.05). Women exhibited higher ADP-inducible platelet aggregation in response to both 10 μM and 5 μM of ADP (both p < 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 p < 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 (p < 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 p > 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 (p = 0.01). Conclusions: 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.
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