title: Ticagrelor enhances adenosine-induced coronary vasodilatory responses in humans.
abstract: OBJECTIVE
  This study was undertaken to determine if ticagrelor augments adenosine-induced coronary blood flow and the sensation of dyspnea in human subjects.
  
  
  BACKGROUND
  Ticagrelor is a P2Y(12) receptor antagonist that showed superior clinical benefit versus clopidogrel in a phase III trial (PLATO [Platelet Inhibition and Patient Outcomes]). Ticagrelor has been shown to inhibit cell uptake of adenosine and enhance adenosine-mediated hyperemia responses in a dog model.
  
  
  METHODS
  In this double-blind, placebo-controlled study, 40 healthy male subjects were randomized to receive a single dose of ticagrelor (180 mg) or placebo in a crossover fashion. Coronary blood flow velocity (CBFV) was measured by using transthoracic Doppler echocardiography at rest after multiple stepwise adenosine infusions given before and after study drug, and again after the infusion of theophylline.
  
  
  RESULTS
  Ticagrelor significantly increased the area under the curve of CBFV versus the adenosine dose compared with placebo (p = 0.008). There was a significant correlation between ticagrelor plasma concentrations and increases in the area under the curve (p < 0.001). In both treatment groups, the adenosine-induced increase in CBFV was significantly attenuated by theophylline, with no significant differences between subjects receiving ticagrelor or placebo (p = 0.39). Furthermore, ticagrelor significantly enhanced the sensation of dyspnea during adenosine infusion, and the effects were diminished by theophylline.
  
  
  CONCLUSIONS
  Ticagrelor enhanced adenosine-induced CBFV and the sensation of dyspnea in these healthy male subjects via an adenosine-mediated mechanism. (Study to Assess the Effect of Ticagrelor on Coronary Blood Flow in Healthy Male Subjects; NCT01226602).
authors: Department of Clinical and Molecular Medicine, Institution of Medicine, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
authors: Ann
authors: A
authors: Wittfeldt
authors: Håkan
authors: H
authors: Emanuelsson
authors: Gunnar
authors: G
authors: Brandrup-Wognsen
authors: J J J
authors: JJ
authors: van Giezen
authors: Jenny
authors: J
authors: Jonasson
authors: Sven
authors: S
authors: Nylander
authors: Li-Ming
authors: LM
authors: Gan
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects* / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D006801:Humans; D008297:Male; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D000077486:Ticagrelor; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine