title: Ticagrelor increases endothelial progenitor cell level compared to clopidogrel in acute coronary syndromes: A prospective randomized study.
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 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.affiliation: 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.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bonello
authors.affiliation: Vascular Research Center of Marseille, INSERM UMR-S 1076, Aix-Marseille Université, Marseille, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Frere
authors.affiliation: Vascular Research Center of Marseille, INSERM UMR-S 1076, Aix-Marseille Université, Marseille, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Cointe
authors.affiliation: Service de Cardiologie, Centre Hospitalier Universitaire de Marseille, Hôpital NORD, Aix-Marseille Université, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Laine
authors.affiliation: 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.
authors.forename: Julien
authors.initials: J
authors.lastname: Mancini
authors.affiliation: Service de Cardiologie, Centre Hospitalier Universitaire de Marseille, Hôpital NORD, Aix-Marseille Université, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Thuny
authors.affiliation: 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.
authors.forename: François
authors.initials: F
authors.lastname: Kerbaul
authors.affiliation: Service de Cardiologie, CHRU de Lille, Lille, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Lemesle
authors.affiliation: Service de Cardiologie, Centre Hospitalier Universitaire de Marseille, Hôpital NORD, Aix-Marseille Université, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Paganelli
authors.affiliation: Research Unit of Physiology and Pathophysiology in Extreme Oxygenation Conditions (UMR MD2), Faculty of Medicine, Aix-Marseille University, Marseille, France.
authors.forename: Regis
authors.initials: R
authors.lastname: Guieu
authors.affiliation: 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.
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnaud
authors.affiliation: 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.
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.affiliation: 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.
authors.forename: Florence
authors.initials: F
authors.lastname: Sabatier
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D018952:Antigens, CD34 / Q000096:biosynthesis; D015992:Body Mass Index; D000077144:Clopidogrel; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000379:methods; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D018952:Antigens, CD34; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: Endothelial; P2Y12-ADP receptor; Pleiotropic; Progenitor cells; Vascular healing