Platelet reactivity inhibition following ticagrelor loading dose in patients undergoing percutaneous coronary intervention for acute coronary syndrome

Abstract

Background Ticagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared to clopidogrel. Although on‐clopidogrel PR was shown to correlate with ischemia and bleeding events, no study has investigated the relationship between on‐ticagrelor PR and outcome. Objectives We aimed to evaluate the relationship between on‐ticagrelor PR, assessed by the vasodilator‐stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI). Methods We performed a prospective, multicenter observational study on patients treated with PCI for ACS. The VASP index was used to assess PR after ticagrelor loading dose (LD). The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR. Results Among the 530 patients with ACS included, 183 (34.5%) were admitted for ST elevation myocardial infarction. We observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1% ± 16.6%). At 1 month, 21 (3.8%) MACE and 29 (5.5%) bleedings ≥ 2 according to the Bleedings Academic Research Consortium (BARC) scale were recorded. Neither MACE nor bleeding was associated with PR (P = .34 and P = .78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (P = .03). Platelet reactivity was the only factor associated with acute definite stent thrombosis. Conclusion In patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP did not predict MACE or bleeding, but it was significantly associated with the occurrence of definite acute stent thrombosis.

On-Ticagrelor Platelet Reactivity and Clinical Outcome in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome

“…PR was the only factor associated with early definite stent thrombosis at 1 month. 20 This link was not significant at 1 year (p ¼ 0.3). A landmark analysis considering only events occurring after the first month of follow-up confirmed that PR was not associated with BARC !2 or MACE (p ¼ 0.68 and p ¼ 0.71, respectively).…”

“…Despite this gap in evidence, PR has been commonly used as a surrogate endpoint in studies assessing the efficacy and safety of ticagrelor (17)(18)(19)(20). This study, representing an extension of follow up to 1 year of the previously published results at one month (21), aimed to investigate the relationship between on-ticagrelor PR and thrombotic and bleeding events in ACS patients undergoing PCI.…”

P2Y12 Inhibition beyond Thrombosis: Effects on Inflammation

“…This cAMP inhibition is not sufficient to induce platelet aggregation by itself but can promote it [36]. VASP phosphorylation state can be used to monitor the effects of anti P2Y 12 therapy [37,38]. Binding of ADP to P2Y 12 also induces an activation of two isoforms of phosphoinositide-3-kinase-(PI3K) -p110β and p110γ -through the recruitment of βγ subunits of Gi, which is critical for integrin αIIbβ3 (GpIIbIIIa) activation and stabilization of platelet aggregates, especially induced by thrombin or TXA2 [13,[39][40][41][42].…”

Prediction of residual ischemic risk in ticagrelor-treated patients with acute coronary syndrome

“…Compelling evidence from observational studies con rmed the contribution of platelet function tests to the prediction of ischemic events in patients with ACS (8-12). However, most of these studies were based on clopidogrel-treated patients, and the link between platelet reactivity and clinical events in ticagrelortreated patients remains uncertain (13,14). In addition, platelet reactivity with ticagrelor, assessed by the vasodilator-stimulated phosphoprotein (VASP) index, was not found to be associated with bleeding or thrombotic events in ACS patients undergoing percutaneous coronary intervention (PCI) (13).…”