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(Circulation. 2004;109:457-464.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Randomized, Controlled Dose-Ranging Study of the Selective Adenosine A_2A Receptor Agonist Binodenoson for Pharmacological Stress as an Adjunct to Myocardial Perfusion Imaging

James E. Udelson, MD; Gary V. Heller, MD, PhD; Frans J.Th. Wackers, MD; Andrew Chai, MD; David Hinchman, MD; Patrick S. Coleman, MD; Vasken Dilsizian, MD; Marcello DiCarli, MD; Rory Hachamovitch, MD; James R. Johnson, PhD; Richard J. Barrett, PhD; Raymond J. Gibbons, MD

From the Division of Cardiology, Tufts-New England Medical Center, Boston, Mass (J.E.U.); Henry Low Heart Center, Hartford Hospital, Hartford, Conn, and the University of Connecticut School of Medicine, Farmington (G.V.H.); Cardiovascular Division, Yale University School of Medicine, New Haven, Conn (F.J.T.W.); Idaho Cardiology Associates, Boise, Idaho (A.C., D.H.); Northern California Medical Associates, Santa Rosa, Calif (P.S.C.); Division of Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Md (V.D.); Division of Cardiology, University of Southern California Medical School, Los Angeles, Calif (R.H.); Division of Nuclear Medicine, Brigham and Women’s Hospital, Boston, Mass (M.D.); King Pharmaceuticals Research and Development, Cary, NC (J.R.J., R.J.B.); and Cardiovascular Division, Mayo Clinic, Rochester, Minn (R.J.G.).

Correspondence to James E. Udelson, MD, Division of Cardiology, Box 70, Tufts-New England Medical Center, 750 Washington St, Boston, MA 02111. E-mail judelson{at}tufts-nemc.org

Received September 18, 2003; de novo received October 29, 2003; revision received December 3, 2003; accepted December 5, 2003.

Background— Dipyridamole and adenosine cause frequent side effects as a result of nonspecific adenosine receptor stimulation. Selective agonism of the adenosine A_2A receptor should result in a similar degree of coronary vasodilation (and thus similar perfusion images) with fewer side effects.

Methods and 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 A_2A 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 (P0.01) 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 A_2A 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.

Key Words: scintigraphy • adenosine • imaging • nuclear medicine

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