Impact of Platelet Reactivity in ACS Patients on Clinical Outcomes with Triple Antithrombotic Therapy.

Julia Gruttemeier,Noemie Resseguier,Maud Maza,Franck Paganelli,Hermann Yao,Laurent Bonello,Marianne Zeller,Marc Laine,Laurence Camoin-Jau,Emmanuel De Maistre,Yves Cottin

doi:10.3390/jcm10081565

Abstract

Optimal antithrombotic therapy after percutaneous coronary intervention (PCI) in patients on oral anticoagulants (OAC) remains a clinical conundrum. In fact, combining an OAC with dual antiplatelet therapy (triple antithrombotic therapy, TAT) increases the risk of bleeding. Clopidogrel is the only thienopyridine recommended in TAT patients. Whether its response plays a relevant role in this setting remains uncertain. We aimed to evaluate the level of platelet reactivity inhibition (PRI) achieved by oral TAT in Acute Coronary Syndrome (ACS) patients undergoing PCI and its relationship with outcomes. We performed a multicenter prospective observational study and assessed PRI by vasodilator-stimulated phosphoprotein (VASP) index following a loading dose of clopidogrel. The primary endpoint was the incidence of major adverse cerebral or cardiovascular events (MACCE) at six months based on High on Treatment Platelet Reactivity (HTPR, VASP > 50%). The secondary endpoint was the incidence of bleeding at six months based on Low on Treatment Platelet Reactivity (LTPR, VASP < 16%). 491 patients were followed up for six months: 7.7% experienced MACCE and 17.3% experienced bleeding. There was no significant relationship between HTPR and MACCE, neither between LTPR and bleeding. Vitamin-K antagonist (VKA) treatment was associated with more MACCE and bleeding events, and the majority of events occurred within the first months. VASP index failed to predict outcomes in post-ACS patients with TAT. We confirm that direct acting OAC should be prioritized over VKA in TAT regimen.

Highlights

IntroductionTriple antithrombotic therapy (TAT) (combination of oral anticoagulation, oral anticoagulants (OAC), and dual antiplatelet therapy, DAPT) in the setting of acute coronary syndrome (ACS) is increasingly prescribed because of frequent associated co-morbidities [1]
We aimed to investigate the inter-individual variability for platelet reactivity inhibition (PRI) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and receiving Triple antithrombotic therapy (TAT) regimen in order to identify sub-groups at higher risk populations for bleeding or ischemic events regarding High on-treatment platelet reactivity (HTPR) or
Withdrawn informed consent was found in 25 patients, 67 patients were lost to follow-up, PRI was not performed in 182 patients and these were excluded from the statistical analyses

Summary

Introduction

Triple antithrombotic therapy (TAT) (combination of oral anticoagulation, OAC, and dual antiplatelet therapy, DAPT) in the setting of acute coronary syndrome (ACS) is increasingly prescribed because of frequent associated co-morbidities [1]. These patients receive DAPT for the prevention of thrombotic or ischemic events, and oral OAC is recommended in patients with atrial fibrillation (AF), mechanical heart valves and venous thromboembolism [2,3,4,5]. Data from registries have shown that TAT was effective in reducing ischemic events, but with significantly increased risk of bleeding [3,6,7]. As the only thienopyridine recommended in recent guidelines for the TAT regimen, clopidogrel has been shown through platelet function assessment test (PFT) to have a high degree of inter-individual variability for platelet reactivity inhibition (PRI) [8]

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