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Selective adenosine agonists and myocardial perfusion imaging

  • Review Article
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Journal of Nuclear Cardiology Aims and scope

Abstract

Selective adenosine receptor agonists have several advantages for use as stress agents in conjunction with myocardial perfusion imaging compared to the non selective agents such as adenosine and dipyridamole. This review will summarize the pre-clinical and clinical data on the selective adenosine agonist stress agents regadenoson (Lexiscan®), binodenoson (CorVue™) and apadenoson (Stedivaze™) that have been studied so far with focus on regadenoson that has the most clinical data published so far. The article will review the adenosine receptor types and properties. It will also review the various attributes of the selective adenosine agonists including their pharmacology, pharmacokinetics and pharmacodynamics, their coronary vasodilatory and hemodynamic effects, their safety and side effects, their interactions with other drugs and their use with myocardial perfusion imaging. The landmark trials of the selective adenosine agonists will be reviewed as well as their use in special patient populations undergoing stress myocardial perfusion imaging.

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References

  1. Orlandi C. Pharmacology of coronary vasodilation: A brief review. J Nucl Cardiol 1996;3:S27-30.

    Article  PubMed  CAS  Google Scholar 

  2. Kaul S. The role of capillaries in determining coronary blood flow reserve: Implications for stress-induced reversible perfusion defects. J Nucl Cardiol 2001;8:694-700.

    Article  PubMed  CAS  Google Scholar 

  3. Wacker CM, Bauer WR. Myocardial microcirculation in humans—new approaches using MRI. Herz 2003;28:74-81.

    Article  PubMed  Google Scholar 

  4. Zoghbi GJ, Iskandrian AE. Pharmacological stress testing. In: Garcia EV, Iskandrian AE, editors. Nuclear cardiac imaging: Principles and applications. New York: Oxford University Press; 2008. p. 293-315.

    Google Scholar 

  5. Gemignani AS, Abbott BG. The emerging role of the selective A2A agonist in pharmacologic stress testing. J Nucl Cardiol 2010;17:494-7.

    Article  PubMed  Google Scholar 

  6. Olah ME, Stiles GL. Adenosine receptor subtypes: Characterization and therapeutic regulation. Annu Rev Pharmacol Toxicol 1995;35:581-606.

    Article  PubMed  CAS  Google Scholar 

  7. Hendel RC, Jamil T, Glover DK. Pharmacologic stress testing: New methods and new agents. J Nucl Cardiol 2003;10:197-204.

    Article  PubMed  Google Scholar 

  8. Sato A, Terata K, Miura H, Toyama K, Loberiza FR Jr, Hatoum OA, et al. Mechanism of vasodilation to adenosine in coronary arterioles from patients with heart disease. Am J Physiol Heart Circ Physiol 2005;288:H1633-40.

    Article  PubMed  CAS  Google Scholar 

  9. Muller CE, Jacobson KA. Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim Biophys Acta 2010;1808:1290-308.

    PubMed  Google Scholar 

  10. Al Jaroudi W, Iskandrian AE. Regadenoson: A new myocardial stress agent. J Am Coll Cardiol 2009;54:1123-30.

    Article  PubMed  CAS  Google Scholar 

  11. Lieu HD, Shryock JC, von Mering GO, Gordi T, Blackburn B, Olmsted AW, et al. Regadenoson, a selective A2A adenosine receptor agonist, causes dose-dependent increases in coronary blood flow velocity in humans. J Nucl Cardiol 2007;14:514-20.

    Article  PubMed  Google Scholar 

  12. Gordi T, Frohna P, Sun HL, Wolff A, Belardinelli L, Lieu H. A population pharmacokinetic/pharmacodynamic analysis of regadenoson, an adenosine A2A-receptor agonist, in healthy male volunteers. Clin Pharmacokinet 2006;45:1201-12.

    Article  PubMed  CAS  Google Scholar 

  13. Gordi T, Blackburn B, Lieu H. Regadenoson pharmacokinetics and tolerability in subjects with impaired renal function. J Clin Pharmacol 2007;47:825-33.

    Article  PubMed  CAS  Google Scholar 

  14. Barrett RJ, Lamson MJ, Johnson J, Smith WB. Pharmacokinetics and safety of binodenoson after intravenous dose escalation in healthy volunteers. J Nucl Cardiol 2005;12:166-71.

    Article  PubMed  Google Scholar 

  15. Glover DK, Ruiz M, Takehana K, Petruzella FD, Riou LM, Rieger JM, et al. Pharmacological stress myocardial perfusion imaging with the potent and selective A(2A) adenosine receptor agonists ATL193 and ATL146e administered by either intravenous infusion or bolus injection. Circulation 2001;104:1181-7.

    Article  PubMed  CAS  Google Scholar 

  16. Gao Z, Li Z, Baker SP, Lasley RD, Meyer S, Elzein E, et al. Novel short-acting A2A adenosine receptor agonists for coronary vasodilation: Inverse relationship between affinity and duration of action of A2A agonists. J Pharmacol Exp Ther 2001;298:209-18.

    PubMed  CAS  Google Scholar 

  17. Cerqueira MD. The future of pharmacologic stress: Selective A2A adenosine receptor agonists. Am J Cardiol 2004;94:33D-40D. discussion 40D-42D.

    Article  PubMed  CAS  Google Scholar 

  18. Trochu JN, Zhao G, Post H, Xu X, Belardinelli L, Belloni FL, et al. Selective A2A adenosine receptor agonist as a coronary vasodilator in conscious dogs: Potential for use in myocardial perfusion imaging. J Cardiovasc Pharmacol 2003;41:132-9.

    Article  PubMed  CAS  Google Scholar 

  19. Zhao G, Linke A, Xu X, Ochoa M, Belloni F, Belardinelli L, et al. Comparative profile of vasodilation by CVT-3146, a novel A2A receptor agonist, and adenosine in conscious dogs. J Pharmacol Exp Ther 2003;307:182-9.

    Article  PubMed  CAS  Google Scholar 

  20. Mekkaoui C, Jadbabaie F, Dione DP, Meoli DF, Purushothaman K, Belardinelli L, et al. Effects of adenosine and a selective A2A adenosine receptor agonist on hemodynamic and thallium-201 and technetium-99m-sestaMIBI biodistribution and kinetics. JACC Cardiovasc Imaging 2009;2:1198-208.

    Article  PubMed  Google Scholar 

  21. Glover DK, Ruiz M, Yang JY, Koplan BA, Allen TR, Smith WH, et al. Pharmacological stress thallium scintigraphy with 2-cyclohexylmethylidenehydrazinoadenosine (WRC-0470). A novel, short-acting adenosine A2A receptor agonist. Circulation 1996;94:1726-32.

    PubMed  CAS  Google Scholar 

  22. Dhalla AK, Wong MY, Wang WQ, Biaggioni I, Belardinelli L. Tachycardia caused by A2A adenosine receptor agonists is mediated by direct sympathoexcitation in awake rats. J Pharmacol Exp Ther 2006;316:695-702.

    Article  PubMed  CAS  Google Scholar 

  23. Zhao G, Serpllion S, Shryock J, Messina E, Xu X, Ochoa M, et al. Regadenoson, a novel pharmacologic stress agent for use in myocardial perfusion imaging, does not have a direct effect on the QT interval in conscious dogs. J Cardiovasc Pharmacol 2008;52:467-73.

    Article  PubMed  CAS  Google Scholar 

  24. Zhao G, Messina E, Xu X, Ochoa M, Sun HL, Leung K, et al. Caffeine attenuates the duration of coronary vasodilation and changes in hemodynamics induced by regadenoson (CVT-3146), a novel adenosine A2A receptor agonist. J Cardiovasc Pharmacol 2007;49:369-75.

    Article  PubMed  CAS  Google Scholar 

  25. Hodgson JM, Dib N, Kern MJ, Bach RG, Barrett RJ. Coronary circulation responses to binodenoson, a selective adenosine A2A receptor agonist. Am J Cardiol 2007;99:1507-12.

    Article  PubMed  CAS  Google Scholar 

  26. Kern MJ, Hodgson JM, Dib N, Mittleman RS, Crane PD. Effects of apadenoson, a selective adenosine A2a receptor agonis for myocardial perfusion imaging, on coronary blood flow velocity in conscious patients. Circulation 2006;114:582. (Abstract).

    Article  Google Scholar 

  27. Hendel RC, Bateman TM, Cerqueira MD, Iskandrian AE, Leppo JA, Blackburn B, et al. Initial clinical experience with regadenoson, a novel selective A2A agonist for pharmacologic stress single-photon emission computed tomography myocardial perfusion imaging. J Am Coll Cardiol 2005;46:2069-75.

    Article  PubMed  CAS  Google Scholar 

  28. Iskandrian AE, Bateman TM, Belardinelli L, Blackburn B, Cerqueira MD, Hendel RC, et al. Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: Results of the ADVANCE phase 3 multicenter international trial. J Nucl Cardiol 2007;14:645-58.

    Article  PubMed  Google Scholar 

  29. Hage FG, Heo J, Franks B, Belardinelli L, Blackburn B, Wang W, et al. Differences in heart rate response to adenosine and regadenoson in patients with and without diabetes mellitus. Am Heart J 2009;157:771-6.

    Article  PubMed  CAS  Google Scholar 

  30. Hage FG, Perry G, Heo J, Iskandrian AE. Blunting of the heart rate response to adenosine and regadenoson in relation to hyperglycemia and the metabolic syndrome. Am J Cardiol 2010;105:839-43.

    Article  PubMed  CAS  Google Scholar 

  31. Udelson JE, Heller GV, Wackers FJ, Chai A, Hinchman D, Coleman PS, et al. Randomized, controlled dose-ranging study of the selective adenosine A2A receptor agonist binodenoson for pharmacological stress as an adjunct to myocardial perfusion imaging. Circulation 2004;109:457-64.

    Article  PubMed  CAS  Google Scholar 

  32. Gaemperli O, Schepis T, Koepfli P, Siegrist PT, Fleischman S, Nguyen P, et al. Interaction of caffeine with regadenoson-induced hyperemic myocardial blood flow as measured by positron emission tomography: A randomized, double-blind, placebo-controlled crossover trial. J Am Coll Cardiol 2008;51:328-9.

    Article  PubMed  Google Scholar 

  33. Mahmarian JJ, Cerqueira MD, Iskandrian AE, Bateman TM, Thomas GS, Hendel RC, et al. Regadenoson induces comparable left ventricular perfusion defects as adenosine: A quantitative analysis from the ADVANCE MPI 2 trial. JACC Cardiovasc Imaging 2009;2:959-68.

    Article  PubMed  Google Scholar 

  34. Cerqueira MD, Nguyen P, Staehr P, Underwood SR, Iskandrian AE. Effects of age, gender, obesity, and diabetes on the efficacy and safety of the selective A2A agonist regadenoson versus adenosine in myocardial perfusion imaging integrated ADVANCE-MPI trial results. JACC Cardiovasc Imaging 2008;1:307-16.

    Article  PubMed  Google Scholar 

  35. Leaker BR, O’Connor B, Hansel TT, Barnes PJ, Meng L, Mathur VS, et al. Safety of regadenoson, an adenosine A2A receptor agonist for myocardial perfusion imaging, in mild asthma and moderate asthma patients: A randomized, double-blind, placebo-controlled trial. J Nucl Cardiol 2008;15:329-36.

    Article  PubMed  Google Scholar 

  36. Thomas GS, Tammelin BR, Schiffman GL, Marquez R, Rice DL, Milikien D, et al. Safety of regadenoson, a selective adenosine A2A agonist, in patients with chronic obstructive pulmonary disease: A randomized, double-blind, placebo-controlled trial (RegCOPD trial). J Nucl Cardiol 2008;15:319-28.

    Article  PubMed  Google Scholar 

  37. Murray JJ, Weiler JM, Schwartz LB, Busse WW, Katial RK, Lockey RF, et al. Safety of binodenoson, a selective adenosine A2A receptor agonist vasodilator pharmacological stress agent, in healthy subjects with mild intermittent asthma. Circ Cardiovasc Imaging 2009;2:492-8.

    Article  PubMed  Google Scholar 

  38. Aljaroudi W, Hermann D, Hage F, Heo J, Iskandrian AE. Safety of regadenoson in patients with end-stage renal disease. Am J Cardiol 2009;105:133-5.

    Article  PubMed  Google Scholar 

  39. Aljaroudi W, Iqbal F, Koneru J, Bhambhvani P, Heo J, Iskandrian AE. Safety of regadenoson in patients with end-stage liver disease. J Nucl Cardiol 2011;18:90-5.

    Article  PubMed  Google Scholar 

  40. Thomas GS, Thompson RC, Miyamoto MI, Ip TK, Rice DL, Milikien D, et al. The RegEx trial: A randomized, double-blind, placebo- and active-controlled pilot study combining regadenoson, a selective A(2A) adenosine agonist, with low-level exercise, in patients undergoing myocardial perfusion imaging. J Nucl Cardiol 2009;16:63-72.

    Article  PubMed  Google Scholar 

  41. Kwon DH, Cerqueira MD, Young R, Houghtaling P, Lieber E, Menon V, et al. Lessons from regadenoson and low-level treadmill/regadenoson myocardial perfusion imaging: Initial clinical experience in 1263 patients. J Nucl Cardiol 2010;17:853-7.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Cardiovascular Disease, The University of Alabama at Birmingham, FOT 920, 1960 6th Avenue South, Birmingham, AL, 35294, USA

    Gilbert J. Zoghbi MD & Ami E. Iskandrian MD

  2. Birmingham VA Medical Center, Birmingham, AL, USA

    Gilbert J. Zoghbi MD

Authors
  1. Gilbert J. Zoghbi MD
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  2. Ami E. Iskandrian MD
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Correspondence to Gilbert J. Zoghbi MD.

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Zoghbi, G.J., Iskandrian, A.E. Selective adenosine agonists and myocardial perfusion imaging. J. Nucl. Cardiol. 19, 126–141 (2012). https://doi.org/10.1007/s12350-011-9474-9

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  • DOI: https://doi.org/10.1007/s12350-011-9474-9

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