Randomized, controlled dose-ranging study of the selective adenosine A2A receptor agonist binodenoson for pharmacological stress as an adjunct to myocardial perfusion imaging.
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.
Udelson
James E
JE
Division of Cardiology, Tufts-New England Medical Center, 750 Washington St, Boston, Mass 02111, USA. judelson@tufts-nemc.org
Heller
Gary V
GV
Wackers
Frans J Th
FJ
Chai
Andrew
A
Hinchman
David
D
Coleman
Patrick S
PS
Dilsizian
Vasken
V
DiCarli
Marcello
M
Hachamovitch
Rory
R
Johnson
James R
JR
Barrett
Richard J
RJ
Gibbons
Raymond J
RJ
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
D058908:Adenosine A2 Receptor Agonists; D014665:Vasodilator Agents; D000241:Adenosine; C101949:binodenoson