title: Ticagrelor increases adenosine plasma concentration in patients with an acute coronary syndrome.
abstract: OBJECTIVE
  This study aimed to investigate the impact of ticagrelor on adenosine plasma concentration (APC) in acute coronary syndrome (ACS) patients.
  
  
  BACKGROUND
  Ticagrelor is a direct-acting P2Y12-adenosine diphosphate receptor blocker. The clinical benefit of ticagrelor compared with clopidogrel in ACS patients suggests that the drug has non-platelet-directed properties. Animal and in vitro models suggested that the "pleiotropic" properties of ticagrelor may be related to an interaction with adenosine metabolism.
  
  
  METHODS
  We prospectively randomized 60 ACS patients to receive ticagrelor or clopidogrel. The APC was measured by liquid chromatography. To assess the mechanism of APC variation, we measured adenosine deaminase concentration, adenosine uptake by red blood cells, and cyclic adenosine monophosphate production by cells overexpressing adenosine receptors. The P2Y12-adenosine diphosphate receptor blockade was assessed by the vasodilator-stimulated phosphoprotein index.
  
  
  RESULTS
  Patients receiving ticagrelor had significantly higher APC than patients receiving clopidogrel (1.5 μM [interquartile range: 0.98 to 1.7 μM] vs. 0.68 μM [interquartile range: 0.49 to 0.78 μM]; p < 0.01). The APC was not correlated with vasodilator-stimulated phosphoprotein (p = 0.16). Serum-containing ticagrelor inhibited adenosine uptake by red blood cells compared with clopidogrel or controls (p < 0.01 for both comparisons). Adenosine deaminase activity was similar in serum of patients receiving clopidogrel or ticagrelor (p = 0.1). Ticagrelor and clopidogrel had no direct impact on adenosine receptors (p = not significant).
  
  
  CONCLUSIONS
  Ticagrelor increases APC in ACS patients compared with clopidogrel by inhibiting adenosine uptake by red blood cells.
authors.affiliation: Département de Cardiologie, Hôpital Universitaire Nord de Marseille, Assistance-Publique Hôpitaux de Marseille, Marseille, France; INSERM UMRS 1076, Aix-Marseille University, Marseille, France. Electronic address: laurentbonello@yahoo.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bonello
authors.affiliation: Département de Cardiologie, Hôpital Universitaire Nord de Marseille, Assistance-Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Laine
authors.affiliation: Research Unit of Physiology and Dysoxia and suractivity, UMR MD2 and Institute of Biological Research, French Defense Ministry (IRBA), Marseille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kipson
authors.affiliation: Assistance Publique, Hôpitaux de Marseille, Hôpital de la Timone, SSPIM, France; Aix-Marseille Université, Faculté de Médecine de Marseille, LERTIM (EA 3283), Marseille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Mancini
authors.affiliation: Département de Cardiologie, Hôpital Universitaire Nord de Marseille, Assistance-Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Olfa
authors.initials: O
authors.lastname: Helal
authors.affiliation: Research Unit of Physiology and Dysoxia and suractivity, UMR MD2 and Institute of Biological Research, French Defense Ministry (IRBA), Marseille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Fromonot
authors.affiliation: Research Unit of Physiology and Dysoxia and suractivity, UMR MD2 and Institute of Biological Research, French Defense Ministry (IRBA), Marseille, France.
authors.forename: Vlad
authors.initials: V
authors.lastname: Gariboldi
authors.affiliation: Research Unit of Physiology and Dysoxia and suractivity, UMR MD2 and Institute of Biological Research, French Defense Ministry (IRBA), Marseille, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Condo
authors.affiliation: Département de Cardiologie, Hôpital Universitaire Nord de Marseille, Assistance-Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Thuny
authors.affiliation: INSERM UMRS 1076, Aix-Marseille University, Marseille, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Frere
authors.affiliation: INSERM UMRS 1076, Aix-Marseille University, Marseille, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Camoin-Jau
authors.affiliation: Département de Cardiologie, Hôpital Universitaire Nord de Marseille, Assistance-Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Paganelli
authors.affiliation: INSERM UMRS 1076, Aix-Marseille University, Marseille, France; Laboratoire d'Hématologie et de Biologie Vasculaire, Assistance-Publique Hôpitaux de Marseille, Centre Universitaire de la Conception, Marseille, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.affiliation: Research Unit of Physiology and Dysoxia and suractivity, UMR MD2 and Institute of Biological Research, French Defense Ministry (IRBA), Marseille, France; Laboratoire de Biochimie, Hôpital Universitaire Nord de Marseille, Assistance-Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Regis
authors.initials: R
authors.lastname: Guieu
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000188:drug therapy*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D000243:Adenosine Deaminase / Q000378:metabolism; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002853:Chromatography, Liquid; D000077144:Clopidogrel; D000242:Cyclic AMP / Q000097:blood; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D002097:C-Reactive Protein; D000077144:Clopidogrel; D000242:Cyclic AMP; D000243:Adenosine Deaminase; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: P2Y(12)-ADP receptor blockers; acute coronary syndromes; adenosine; clopidogrel; ticagrelor