title: Randomized, controlled dose-ranging study of the selective adenosine A2A receptor agonist binodenoson for pharmacological stress as an adjunct to myocardial perfusion imaging.
abstract: BACKGROUND
  Dipyridamole and adenosine cause frequent side effects as a result of nonspecific adenosine receptor stimulation. Selective agonism of the adenosine A2A receptor should result in a similar degree of coronary vasodilation (and thus similar perfusion images) with fewer side effects.
  
  
  RESULTS
  In a multicenter, randomized, single-blind, 2-arm crossover trial, 240 patients underwent 2 single photon emission computed tomographic (SPECT) imaging studies in random order, first after pharmacological stress with adenosine and a second study with the selective adenosine A2A receptor agonist binodenoson, using 1 of 4 dosing regimens. Safety, tolerability, and SPECT image concordance between the 2 agents were examined. Exact categorical agreement in the extent and severity of reversible perfusion defects ranged from 79% to 87%, with kappa values from 0.69 to 0.85, indicating very good to excellent agreement between binodenoson and adenosine. The risk of any safety event/side effect was significantly lower with any dose of binodenoson than with adenosine (P< or =0.01) because of a dose-related reduction in subjective side effects, as objective events were infrequent. There was a reduction in the severity of chest pain, dyspnea, and flushing in all binodenoson doses compared with adenosine (P<0.01), and the magnitude of severity reduction was dose-related.
  
  
  CONCLUSIONS
  The selective adenosine A2A receptor agonist binodenoson results in an extent and severity of reversible perfusion defects on SPECT imaging similar to nonselective adenosine receptor stimulation, accompanied by a dose-related reduction in the incidence and severity of side effects.
authors.affiliation: Division of Cardiology, Tufts-New England Medical Center, 750 Washington St, Boston, Mass 02111, USA. judelson@tufts-nemc.org
authors.forename: James E
authors.initials: JE
authors.lastname: Udelson
authors.forename: Gary V
authors.initials: GV
authors.lastname: Heller
authors.forename: Frans J Th
authors.initials: FJ
authors.lastname: Wackers
authors.forename: Andrew
authors.initials: A
authors.lastname: Chai
authors.forename: David
authors.initials: D
authors.lastname: Hinchman
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Coleman
authors.forename: Vasken
authors.initials: V
authors.lastname: Dilsizian
authors.forename: Marcello
authors.initials: M
authors.lastname: DiCarli
authors.forename: Rory
authors.initials: R
authors.lastname: Hachamovitch
authors.forename: James R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Barrett
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Gibbons
mesh_terms: D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives; D058908:Adenosine A2 Receptor Agonists; D000368:Aged; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging*; D003326:Coronary Circulation; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D010477:Perfusion / Q000379:methods; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014665:Vasodilator Agents / Q000009:adverse effects
chemical_list: D058908:Adenosine A2 Receptor Agonists; D014665:Vasodilator Agents; D000241:Adenosine; C101949:binodenoson