PO145 | KINETIC ASSESSMENT OF PLATELET REACTIVITY DURING DUAL ANTIPLATELET THERAPY IN ACUTE CORONARY SYNDROMES: PRELIMINARY RESULTS FROM AN ONGOING STUDY
Abstract
Background and aims. Dual antiplatelet therapy (DAPT) with aspirin and a P2Y₁₂ receptor inhibitor represents the gold standard for patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). Clopidogrel and prasugrel achieve irreversible P2Y₁₂ receptor inhibition, similarly to the irreversible action of aspirin on cyclooxygenase 1 (COX 1), whereas ticagrelor exerts reversible P2Y₁₂ blockade. Despite the irreversible nature of aspirin, accelerated recovery of COX 1 activity within 24 hours has been described in a subset of patients, resulting in suboptimal platelet inhibition and residual high on treatment platelet reactivity (HPR), possibly due to higher platelets turnover. The present study aimed to characterize the kinetics of platelet reactivity over the dosing interval during DAPT and to investigate whether a similar recovery of pharmacological target activity occurs for P2Y₁₂ inhibitors within 24 h, as observed for aspirin, using multiple platelet function assays. Methods. Patients with ACS undergoing PCI and treated with guideline‑recommended DAPT (aspirin plus clopidogrel, prasugrel or ticagrelor) were prospectively enrolled. Platelet function was assessed at two time points, T1 (10 h after drug intake) and T2 (12 h for ticagrelor and 24 h for prasugrel and clopidogrel), to evaluate platelet inhibition across the dosing interval. P2Y₁₂ inhibition was assessed by light transmission aggregometry (LTA), VerifyNow P2Y₁₂ and VASP phosphorylation. Changes in target recovery rate were quantified by the T1–T2 slope (T2‑T1/14). Recruitment is ongoing and this is an interim analysis. Results. Platelet reactivity kinetics differed according to the P2Y₁₂ inhibitor used. In patients treated with clopidogrel, VerifyNow P2Y₁₂ reaction units (PRU) were consistently higher at both T1 and T2 compared with patients receiving ticagrelor or prasugrel (p < 0.05), indicating greater residual P2Y₁₂ dependent HPR over the dosing interval. In addition, the increase in PRU slope was greater in clopidogrel treated patients compared with those treated with ticagrelor (p= 0.0226) (A). Consequently, platelet reactivity index (PRI) values measured by VASP were higher at both time points in clopidogrel treated patients compared with those receiving ticagrelor or prasugrel (p < 0.05) (B). Likewise, ADP induced platelet aggregation at all tested concentrations (2, 5 and 10 µM) was greater in clopidogrel treated patients than in ticagrelor treated patients (C). Recovery of P2Y₁₂ dependent platelet reactivity was further modulated by biological factors. Regardless of the drugs, the slope of PRI was significantly higher in men (Rho = 0.466; p = 0.001) (D), and a comparable sex related effect was observed for ADP induced LTA at low agonist concentration (2 µM; Rho = 0.384; p = 0.015) (E). Conclusions. In this preliminary analysis, variability in the recovery rate of platelet reactivity over the dosing interval, previously described for aspirin, also occurs for the P2Y₁₂ pathway. Despite irreversible receptor inhibition, patients treated with clopidogrel exhibit greater residual and P2Y₁₂ dependent platelet reactivity compared with those receiving ticagrelor and prasugrel over the dosing interval. This recovery seems to be sex-influenced and suggests that pharmacodynamic recovery of platelet function represents an additional mechanism, beyond impaired bioactivation, contributing to suboptimal response to clopidogrel.
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BibTeX
@article{marco2026po145,
title = {{PO145 | KINETIC ASSESSMENT OF PLATELET REACTIVITY DURING DUAL ANTIPLATELET THERAPY IN ACUTE CORONARY SYNDROMES: PRELIMINARY RESULTS FROM AN ONGOING STUDY}},
author = {Beatrice Di Marco},
journal = {Bleeding, Thrombosis and Vascular Biology},
year = {2026},
month = oct,
url = {https://www.btvb.org/btvb/article/view/961},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - PO145 | KINETIC ASSESSMENT OF PLATELET REACTIVITY DURING DUAL ANTIPLATELET THERAPY IN ACUTE CORONARY SYNDROMES: PRELIMINARY RESULTS FROM AN ONGOING STUDY
AU - Beatrice Di Marco
PY - 2026
DA - 2026/10/26
JO - Bleeding, Thrombosis and Vascular Biology
UR - https://www.btvb.org/btvb/article/view/961
AB - Background and aims. Dual antiplatelet therapy (DAPT) with aspirin and a P2Y₁₂ receptor inhibitor represents the gold standard for patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). Clopidogrel and prasugrel achieve irreversible P2Y₁₂ receptor inhibition, similarly to the irreversible action of aspirin on cyclooxygenase 1 (COX 1), whereas ticagrelor exerts reversible P2Y₁₂ blockade. Despite the irreversible nature of aspirin, accelerated recovery of COX 1 activity within 24 hours has been described in a subset of patients, resulting in suboptimal platelet inhibition and residual high on treatment platelet reactivity (HPR), possibly due to higher platelets turnover. The present study aimed to characterize the kinetics of platelet reactivity over the dosing interval during DAPT and to investigate whether a similar recovery of pharmacological target activity occurs for P2Y₁₂ inhibitors within 24 h, as observed for aspirin, using multiple platelet function assays. Methods. Patients with ACS undergoing PCI and treated with guideline‑recommended DAPT (aspirin plus clopidogrel, prasugrel or ticagrelor) were prospectively enrolled. Platelet function was assessed at two time points, T1 (10 h after drug intake) and T2 (12 h for ticagrelor and 24 h for prasugrel and clopidogrel), to evaluate platelet inhibition across the dosing interval. P2Y₁₂ inhibition was assessed by light transmission aggregometry (LTA), VerifyNow P2Y₁₂ and VASP phosphorylation. Changes in target recovery rate were quantified by the T1–T2 slope (T2‑T1/14). Recruitment is ongoing and this is an interim analysis. Results. Platelet reactivity kinetics differed according to the P2Y₁₂ inhibitor used. In patients treated with clopidogrel, VerifyNow P2Y₁₂ reaction units (PRU) were consistently higher at both T1 and T2 compared with patients receiving ticagrelor or prasugrel (p < 0.05), indicating greater residual P2Y₁₂ dependent HPR over the dosing interval. In addition, the increase in PRU slope was greater in clopidogrel treated patients compared with those treated with ticagrelor (p= 0.0226) (A). Consequently, platelet reactivity index (PRI) values measured by VASP were higher at both time points in clopidogrel treated patients compared with those receiving ticagrelor or prasugrel (p < 0.05) (B). Likewise, ADP induced platelet aggregation at all tested concentrations (2, 5 and 10 µM) was greater in clopidogrel treated patients than in ticagrelor treated patients (C). Recovery of P2Y₁₂ dependent platelet reactivity was further modulated by biological factors. Regardless of the drugs, the slope of PRI was significantly higher in men (Rho = 0.466; p = 0.001) (D), and a comparable sex related effect was observed for ADP induced LTA at low agonist concentration (2 µM; Rho = 0.384; p = 0.015) (E). Conclusions. In this preliminary analysis, variability in the recovery rate of platelet reactivity over the dosing interval, previously described for aspirin, also occurs for the P2Y₁₂ pathway. Despite irreversible receptor inhibition, patients treated with clopidogrel exhibit greater residual and P2Y₁₂ dependent platelet reactivity compared with those receiving ticagrelor and prasugrel over the dosing interval. This recovery seems to be sex-influenced and suggests that pharmacodynamic recovery of platelet function represents an additional mechanism, beyond impaired bioactivation, contributing to suboptimal response to clopidogrel.
SN - 2785-5309
ER -