Marc Laine1, Corinne Frere2, Thomas Cuisset3, Franck Paganelli4, Pierre-Emmanuel Morange5, Francoise Dignat-George2, Julie Berbis6, Laurence Camoin-Jau7, Laurent Bonello8. 1. Service de cardiologie, Centre hospitalo-universitaire, Aix-Marseille université, Assistance-Publique Hôpitaux de Marseille, Marseille, France; MARS cardio, Mediterranean Association for Research and Studies in Cardiology, Hôpital Nord, Marseille, France. 2. Aix-Marseille Université, INSERM UMR-S 1076, Vascular Research Center of Marseille, Marseille, France; Service d'hématologie Biologique, Centre hospitalo-universitaire Timone, Assistance-Publique Hôpitaux de Marseille, Marseille, France. 3. Département de cardiologie, Centre hospitalo-universitaire Timone, Assistance-Publique Hôpitaux de Marseille, Marseille, France; Aix-Marseille Université, INSERM UMR1062, INRA UMR1260, Nutrition, Obesity and Risk of Thrombosis, Marseille, France. 4. Service de cardiologie, Centre hospitalo-universitaire, Aix-Marseille université, Assistance-Publique Hôpitaux de Marseille, Marseille, France. 5. Service d'hématologie Biologique, Centre hospitalo-universitaire Timone, Assistance-Publique Hôpitaux de Marseille, Marseille, France; Aix-Marseille Université, INSERM UMR1062, INRA UMR1260, Nutrition, Obesity and Risk of Thrombosis, Marseille, France. 6. Aix-Marseille Université, Department of Biostatistics, Marseille, France. 7. Service d'hématologie Biologique, Centre hospitalo-universitaire Timone, Assistance-Publique Hôpitaux de Marseille, Marseille, France. 8. Service de cardiologie, Centre hospitalo-universitaire, Aix-Marseille université, Assistance-Publique Hôpitaux de Marseille, Marseille, France; MARS cardio, Mediterranean Association for Research and Studies in Cardiology, Hôpital Nord, Marseille, France; Service d'hématologie Biologique, Centre hospitalo-universitaire Timone, Assistance-Publique Hôpitaux de Marseille, Marseille, France. Electronic address: laurentbonello@yahoo.fr.
Abstract
BACKGROUND: Clinical trials have demonstrated an excess of acute stent thrombosis (AST) in acute coronary syndromes patients (ACS) undergoing percutaneous coronary intervention (PCI) withbivalirudin compared to heparin. We aimed to investigate the potential mechanisms responsible for thrombus formation under bivalirudin. METHODS: We compared heparin and bivalirudin during PCI for ACS in a prospective monocentre randomized study. Twenty patients were included aftercoronary angiography and received a loading dose (LD) of 180mg of ticagrelor at the time of PCI. They were randomly assigned to heparin (70UI/kg) intra-venous (IV) bolus or bivalirudin IV bolus of 0.75mg/kg followed by an infusion of 1.75mg/kg/h until the end of the PCI. The VASP index and thrombin generation test were used to assess the course of platelet reactivity (PR) and thrombin generation. RESULTS:Thrombin generation and PR were identical in both groups at baseline. There was no difference in the course of PR following the LD over time. An optimal PR inhibition was reached 4h after the LD of ticagrelor. Heparin and bivalirudin infusion effectively inhibited thrombin generation during PCI. However, 4h after the end of bivalirudin infusion, thrombin generation had returned to its baseline value whereas in the heparin group it remained significantly inhibited compared to baseline and to the bivalirudin group 4h after the end of the infusion (p<0.01 and p<0.02 respectively). CONCLUSIONS: The present study suggests that the short half-life of bivalirudin and the quick restoration of thrombin activity at a time when optimal PR is not reached may be responsible for acute stent thrombosis. Clinicaltrial.gov: NCT02428725.
RCT Entities:
BACKGROUND: Clinical trials have demonstrated an excess of acute stent thrombosis (AST) in acute coronary syndromespatients (ACS) undergoing percutaneous coronary intervention (PCI) with bivalirudin compared to heparin. We aimed to investigate the potential mechanisms responsible for thrombus formation under bivalirudin. METHODS: We compared heparin and bivalirudin during PCI for ACS in a prospective monocentre randomized study. Twenty patients were included after coronary angiography and received a loading dose (LD) of 180mg of ticagrelor at the time of PCI. They were randomly assigned to heparin (70UI/kg) intra-venous (IV) bolus or bivalirudin IV bolus of 0.75mg/kg followed by an infusion of 1.75mg/kg/h until the end of the PCI. The VASP index and thrombin generation test were used to assess the course of platelet reactivity (PR) and thrombin generation. RESULTS:Thrombin generation and PR were identical in both groups at baseline. There was no difference in the course of PR following the LD over time. An optimal PR inhibition was reached 4h after the LD of ticagrelor. Heparin and bivalirudin infusion effectively inhibited thrombin generation during PCI. However, 4h after the end of bivalirudin infusion, thrombin generation had returned to its baseline value whereas in the heparin group it remained significantly inhibited compared to baseline and to the bivalirudin group 4h after the end of the infusion (p<0.01 and p<0.02 respectively). CONCLUSIONS: The present study suggests that the short half-life of bivalirudin and the quick restoration of thrombin activity at a time when optimal PR is not reached may be responsible for acute stent thrombosis. Clinicaltrial.gov: NCT02428725.
Authors: Nso Nso; Mahmoud Nassar; Milana Zirkiyeva; Yolanda Mbome; Anthony Lyonga Ngonge; Solomon O Badejoko; Shahzad Akbar; Atika Azhar; Sofia Lakhdar; Laura M Guzman Perez; Yousef Abdalazeem; Vincent Rizzo; Most Munira Journal: Cureus Date: 2022-04-09
Authors: Flávia B B Arantes; Fernando R Menezes; Andre Franci; Carlos J D G Barbosa; Talia F Dalçoquio; Carlos A K Nakashima; Luciano M Baracioli; Remo H M Furtado; Quintiliano S S Nomelini; José A F Ramires; Roberto Kalil Filho; José C Nicolau Journal: Adv Ther Date: 2019-11-22 Impact factor: 3.845