Laurent Bonello1, Corinne Frere2, Sylvie Cointe2, Marc Laine3, Julien Mancini4, Franck Thuny3, François Kerbaul5, Gilles Lemesle6, Franck Paganelli3, Regis Guieu7, Laurent Arnaud8, Françoise Dignat-George8, Florence Sabatier8. 1. Service de Cardiologie, Centre Hospitalier Universitaire de Marseille, Hôpital NORD, Aix-Marseille Université, France; Vascular Research Center of Marseille, INSERM UMR-S 1076, Aix-Marseille Université, Marseille, France. Electronic address: laurentbonello@yahoo.fr. 2. Vascular Research Center of Marseille, INSERM UMR-S 1076, Aix-Marseille Université, Marseille, France. 3. Service de Cardiologie, Centre Hospitalier Universitaire de Marseille, Hôpital NORD, Aix-Marseille Université, France. 4. Assistance Publique-Hôpitaux de Marseille, Hôpital de la Timone, BiosTIC, France; Aix-Marseille Université, Inserm, IRD, UMR_S912, SESSTIM, Faculté de Médecine de Marseille, France. 5. Research Unit of Physiology and Pathophysiology in Extreme Oxygenation Conditions (UMR MD2), Faculty of Medicine, Aix-Marseille University, Marseille, France; Pole RUSH, Assistance-Publique Hôpitaux de Marseille, Marseille, France. 6. Service de Cardiologie, CHRU de Lille, Lille, France. 7. Research Unit of Physiology and Pathophysiology in Extreme Oxygenation Conditions (UMR MD2), Faculty of Medicine, Aix-Marseille University, Marseille, France. 8. Vascular Research Center of Marseille, INSERM UMR-S 1076, Aix-Marseille Université, Marseille, France; Laboratoire d'Hématologie et de Biologie Vasculaire, Assistance-Publique Hôpitaux de Marseille, Centre hospitalo-universitaire de la Conception, Marseille, France.
Abstract
BACKGROUND: The clinical benefit of ticagrelor compared to clopidogrel in ACS patients suggested off-target property. Such pleiotropic effect could be mediated by circulating endothelial progenitor cells (EPC) which are critical for vascular healing. We aimed to investigate the impact of ticagrelor on EPC in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). METHODS: We prospectively randomized 106 ACS patients toticagrelor or clopidogrel. Sub-populations of CD34+ circulating progenitor cells (PC) were analyzed by flow cytometry allowing one to determine the levels of CD34+ PC, CD34+CD45+ Hematopoietic PC, CD34+133+ immature PC and CD34+KDR+ EPC on admission and at 1 month. Changes in PC level were calculated as the difference between 1 month and baseline value. RESULTS: The 2 groups were similar regarding baseline characteristics including PC numbers on admission. The 2 groups had similar change in overall CD34+ PC and hematopoietic CD34+45+ PC level (p=0.2). On the contrary, when considering CD34+133+ PC and CD34+KDR+ EPC, we observed that patients treated by ticagrelor had a significantly higher increase in levels of these PC subtypes compared to those treated by clopidogrel (0.23 (-0.33; 0.79) vs 0.00 (-0.5; 0.34); p=0.04 and 0.01 (-0.04; 0.05) vs -0.01 (-0.06; 0.03); p=0.02). Changes in the level of CD34+CD133+ PC correlated with platelet activity measured by the VASP index (r=-0.30; p=0.008). By contrast the increase in the level of CD34+KDR+ EPC in the ticagrelor group was independent of platelet activity. CONCLUSIONS:Ticagrelor increases the number of EPC in ACS patients suggesting a benefit on endothelial regeneration that may participate in the pleiotropic property of the drug.
RCT Entities:
BACKGROUND: The clinical benefit of ticagrelor compared to clopidogrel in ACS patients suggested off-target property. Such pleiotropic effect could be mediated by circulating endothelial progenitor cells (EPC) which are critical for vascular healing. We aimed to investigate the impact of ticagrelor on EPC in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). METHODS: We prospectively randomized 106 ACS patients to ticagrelor or clopidogrel. Sub-populations of CD34+ circulating progenitor cells (PC) were analyzed by flow cytometry allowing one to determine the levels of CD34+ PC, CD34+CD45+ Hematopoietic PC, CD34+133+ immature PC and CD34+KDR+ EPC on admission and at 1 month. Changes in PC level were calculated as the difference between 1 month and baseline value. RESULTS: The 2 groups were similar regarding baseline characteristics including PC numbers on admission. The 2 groups had similar change in overall CD34+ PC and hematopoietic CD34+45+ PC level (p=0.2). On the contrary, when considering CD34+133+ PC and CD34+KDR+ EPC, we observed that patients treated by ticagrelor had a significantly higher increase in levels of these PC subtypes compared to those treated by clopidogrel (0.23 (-0.33; 0.79) vs 0.00 (-0.5; 0.34); p=0.04 and 0.01 (-0.04; 0.05) vs -0.01 (-0.06; 0.03); p=0.02). Changes in the level of CD34+CD133+ PC correlated with platelet activity measured by the VASP index (r=-0.30; p=0.008). By contrast the increase in the level of CD34+KDR+ EPC in the ticagrelor group was independent of platelet activity. CONCLUSIONS:Ticagrelor increases the number of EPC in ACS patients suggesting a benefit on endothelial regeneration that may participate in the pleiotropic property of the drug.
Authors: Michał J Kubisa; Mateusz P Jezewski; Aleksandra Gasecka; Jolanta M Siller-Matula; Marek Postuła Journal: Ther Clin Risk Manag Date: 2018-01-17 Impact factor: 2.423
Authors: Choongki Kim; Byeong Keuk Kim; Sung Jin Hong; Chul Min Ahn; Jung Sun Kim; Young Guk Ko; Donghoon Choi; Myeong Ki Hong; Yangsoo Jang Journal: Yonsei Med J Date: 2018-07 Impact factor: 2.759
Authors: Alejandro Diego-Nieto; Maria B Vidriales; Norberto Alonso-Orcajo; Jose C Moreno-Samos; Francisco Martin-Herrero; Raul Carbonell; Belen Cid; Ignacio Cruz-Gonzalez; Javier C Martin-Moreiras; Carlos Cuellas; Cristina Pascual; Maria Lopez-Benito; Pedro L Sanchez; Felipe Fernandez-Vazquez; Armando Perez de Prado Journal: J Am Heart Assoc Date: 2018-10-02 Impact factor: 5.501