Benefit of Switching Dual Antiplatelet Therapy After Acute Coronary Syndrome According to On-Treatment Platelet Reactivity: The TOPIC-VASP Pre-Specified Analysis of the TOPIC Randomized Study.

Pierre Deharo, Jacques Quilici, Laurence Camoin-Jau, Thomas W Johnson, Clémence Bassez, Guillaume Bonnet, Marianne Fernandez, Manal Ibrahim, Pierre Suchon, Valentine Verdier, Laurent Fourcade, Pierre Emmanuel Morange, Jean Louis Bonnet, Marie Christine Alessi, Thomas Cuisset

Journal: JACC. Cardiovascular interventions 2019;10(24):2560-2570

PMID: 29268886

Abstract

OBJECTIVES

This study sought to evaluate the impact of initial platelet reactivity on the benefit of switched strategy.

BACKGROUND

TOPIC (Timing Of Platelet Inhibition after acute Coronary Syndrome) study suggested that switched dual antiplatelet therapy (DAPT) could improve net clinical benefit after acute coronary syndrome by preventing bleeding.

METHODS

Acute coronary syndrome patients, 1 month after coronary stenting and event free, were randomly assigned to aspirin and clopidogrel (switched DAPT) or continuation of drug regimen (unchanged DAPT). All patients underwent platelet function testing at this time and were classified as low on-treatment platelet reactivity (LTPR) (platelet reactivity index vasodilator-stimulated phosphoprotein ≤20%) or non-LTPR (platelet reactivity index vasodilator-stimulated phosphoprotein >20%). The primary endpoint aimed to evaluate the impact of platelet reactivity on clinical outcomes and benefit of switched DAPT strategy.

RESULTS

A total of 645 patients were included, 305 (47%) of whom were classified as LTPR. LTPR patients were less often diabetic (p = 0.01), had lower body mass index (p < 0.01), and were more often on ticagrelor (p < 0.01). Patients defined as LTPR and randomized to unchanged DAPT were at the highest risk of primary endpoint occurrence (31%; p < 0.01). Conversely, in the switched arm, LTPR patients had no significant difference in primary outcome incidence compared with non-LTPR patients (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.40 to 1.49; p = 0.45). The switched strategy was associated with important reduction in primary endpoint incidence in LTPR patients (HR: 0.29; 95% CI: 0.17 to 0.51; p < 0.01) and only numerically lower incidence in non-LTPR patients (HR: 0.79; 95% CI: 0.46 to 1.35; p = 0.39).

CONCLUSIONS

Switched DAPT was superior regardless of initial platelet reactivity but the benefit was greater in LTPR patients. Indeed, the switched strategy was highly effective in this group, which had impaired prognosis with unchanged DAPT but similar prognosis after switching.

Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Address: Département de Cardiologie, CHU Timone, Marseille, France; "Nutrition, Obesity and Risk of Thrombosis," UMR1062, INSERM, Marseille, France; Faculté de Médecine, Aix-Marseille Université, Marseille, France.; Departement de Cardiologie, Centre Hospitalier de GAP, France.; Laboratoire d'Hématologie, CHU Timone, Marseille, France.; Interventional Cardiology Department, Bristol Heart Institute, Bristol, United Kingdom.; Département de Cardiologie, CHU Timone, Marseille, France; Faculté de Médecine, Aix-Marseille Université, Marseille, France.; Faculté de Médecine, Aix-Marseille Université, Marseille, France; Cardiologie, Hôpital Laveran, Marseille, France.; Faculté de Médecine, Aix-Marseille Université, Marseille, France; Research Unit, asistance publique des hopitaux de Marseille, Unité Médicale des Maladies Auto-Inflammatoires, Marseille, France.; Research Unit, asistance publique des hopitaux de Marseille, Unité Médicale des Maladies Auto-Inflammatoires, Marseille, France.; Cardiologie, Hôpital Laveran, Marseille, France.; "Nutrition, Obesity and Risk of Thrombosis," UMR1062, INSERM, Marseille, France; Faculté de Médecine, Aix-Marseille Université, Marseille, France; Laboratoire d'Hématologie, CHU Timone, Marseille, France; Department of Hematology, CHU Timone, asistance publique des hopitaux de Marseille, Marseille, France.; Département de Cardiologie, CHU Timone, Marseille, France; "Nutrition, Obesity and Risk of Thrombosis," UMR1062, INSERM, Marseille, France; Faculté de Médecine, Aix-Marseille Université, Marseille, France. Electronic address: [email protected].
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