Journal of Nuclear Cardiology

, Volume 22, Issue 2, pp 248–261 | Cite as

Regadenoson provides perfusion results comparable to adenosine in heterogeneous patient populations: A quantitative analysis from the ADVANCE MPI trials

  • John J. Mahmarian
  • Leif E. Peterson
  • Jiaqiong Xu
  • Manuel D. Cerqueira
  • Ami E. Iskandrian
  • Timothy M. Bateman
  • Gregory S. Thomas
  • Faisal Nabi
Original Article



Total and reversible left ventricular (LV) perfusion defect size (PDS) predict patient outcome. Limited data exist as to whether regadenoson induces similar perfusion abnormalities as observed with adenosine. We sought to determine whether regadenoson induces a similar LV PDS as seen with adenosine across varying patient populations.

Methods and Results

ADVANCE MPI were prospective, double-blind randomized trials comparing regadenoson to standard adenosine myocardial perfusion tomography (SPECT). Following an initial adenosine SPECT, patients were randomized to either regadenoson (N = 1284) or a second adenosine study (N = 660). SPECT quantification was performed blinded to randomization and image sequence. Propensity analysis was used to define comparability of regadenoson and adenosine perfusion results. Baseline clinical and SPECT results were similar in the two randomized groups. There was a close correlation between adenosine and regadenoson-induced total (r 2 = 0.98, P < .001) and reversible (r 2 = 0.92, P < .001) PDS. Serial differences in total (0.00 ± 3.51 vs −0.11 ± 3.46, P = .51) and reversible (0.15 ± 3.79 vs 0.07 ± 3.33, P = .65) PDS were also comparable in patients randomized to regadenoson vs adenosine, respectively, and irrespective of age, gender, diabetic status, body mass index, or prior cardiovascular history. By propensity analysis, regadenoson-induced total PDS was significantly larger than observed with adenosine.


This is the first study to show that regadenoson induces similar, if not larger, perfusion defects than those observed with adenosine across different patient populations and demonstrates the value of quantitative analysis for defining serial changes in SPECT perfusion results. Regadenoson should provide comparable diagnostic and prognostic SPECT information to that obtained with adenosine.


A2A adenosine receptor agonists myocardial perfusion imaging: SPECT vasodilator stress 



Drs Mahmarian, Cerqueira, and Thomas are consultants and on the Speakers Bureau for Astellas Pharma, Inc. Dr Bateman has served on Astellas Advisory Boards and has received grant research support from Astellas. The other authors have no conflict of interest.


  1. 1.
    Zoghbi GJ, Iskandrian AE. Coronary artery disease detection: pharmacologic stress. In: Zaret BL, Beller GA, editors. Clinical nuclear cardiology: State of the art and future directions. 3rd ed. Philadelphia: Elsevier Mosby; 2005. p. 233-53.Google Scholar
  2. 2.
    Shaw LJ, Iskandrian AE. Prognostic value of gated myocardial perfusion SPECT. J Nucl Cardiol 2004;11:171-85.PubMedCrossRefGoogle Scholar
  3. 3.
    Mahmarian JJ, Shaw LJ, Filipchuk NG, Dakik HA, Iskander SS, Ruddy TD, et al. A multinational study to establish the value of early adenosine technetium-99m sestamibi myocardial perfusion imaging in identifying a low-risk group for early hospital discharge after acute myocardial infarction. J Am Coll Cardiol 2006;48:2448-57.PubMedCrossRefGoogle Scholar
  4. 4.
    Nabi F, Chang SM, Xu J, Gigliotti E, Mahmarian JJ. Assessing risk in acute chest pain: The value of stress myocardial perfusion imaging in patients admitted through the emergency department. J Nucl Cardiol 2012;19:233-43.PubMedCrossRefGoogle Scholar
  5. 5.
    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. J Am Coll Cardiol CV Imaging 2009;2:959-68.Google Scholar
  6. 6.
    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.PubMedCrossRefGoogle Scholar
  7. 7.
    Hansen CL, Goldstein RA, Akinboboye OO, Berman DS, Botvinick EH, Churchwell KB, et al. Myocardial perfusion and function: single photon emission computed tomography. J Nucl Cardiol 2007;14:e39-60.PubMedCrossRefGoogle Scholar
  8. 8.
    Ficaro EP, Lee BC, Kritzman JN, Corbett JR, Corridor DM. The Michigan method for quantitative nuclear cardiology. J Nucl Cardiol 2007;14:455-65.PubMedCrossRefGoogle Scholar
  9. 9.
    Mahmarian JJ, Moye LA, Verani MS, Bloom MF, Pratt CM. High reproducibility of myocardial perfusion defects in patients undergoing serial exercise thallium-201 tomography. Am J Cardiol 1994;75:1116-9.CrossRefGoogle Scholar
  10. 10.
    Shaw LJ, Berman DS, Maron DJ, Mancini GB, Hayes SW, Hartigan PM, et al. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation 2008;117:1283-91.PubMedCrossRefGoogle Scholar
  11. 11.
    Mahmarian JJ, Dakik HA, Filipchuk NG, Shaw LJ, Iskander SS, Ruddy TD, et al. An initial strategy of intensive medical therapy is comparable to that of coronary revascularization for suppression of scintigraphic ischemia in high-risk but stable survivors of acute myocardial infarction. J Am Coll Cardiol 2006;48:2458-67.PubMedCrossRefGoogle Scholar
  12. 12.
    Mahmarian JJ. Monitoring Medical Therapy: The role of noninvasive imaging. In: Dilsizian V, Narula J, Braunwald E, editors. Atlas of nuclear cardiology. 2nd ed. Philadelphia, PA: Current Medicine; 2006. p. 191-210.Google Scholar
  13. 13.
    Iqbal FM, Hage FG, Ahmed A, Dean PJ, Raslan S, Heo J, et al. Comparison of the prognostic value of normal regadenoson with normal adenosine myocardial perfusion imaging with propensity score matching. J Am Coll Cardiol Imaging 2012;5:1014-21.CrossRefGoogle Scholar
  14. 14.
    Bhatti S, Hakeem A, Dhanalakota S, Palani G, Husain Z, Jacobsen G, et al. Prognostic value of regadenoson myocardial single-photon emission computed tomography in patients with different degrees of renal dysfunction. Eur Heart J Cardiovasc Imaging 2014;15:933-40.PubMedCrossRefGoogle Scholar
  15. 15.
    Wilson RF, Wyche K, Christensen BV, Zimmer S, Laxson DD. Effects of adenosine on human coronary arterial circulation. Circulation 1990;82:1595-606.PubMedCrossRefGoogle Scholar
  16. 16.
    Belardinelli L, Shryock JC, Snowdy S, Zhang Y, Monopoli A, Lozza G, et al. The A2A adenosine receptor mediates coronary vasodilation. J Pharmacol Exp Ther 1998;284:1066-73.PubMedGoogle Scholar
  17. 17.
    Cerqueira MD. The future of pharmacologic stress: Selective A2A adenosine receptor agonists. Am J Cardiol 2004;94:33D-42D.PubMedCrossRefGoogle Scholar
  18. 18.
    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.PubMedCrossRefGoogle Scholar
  19. 19.
    Kaul S, Jayaweera AR. Coronary and myocardial blood volumes. Non-invasive tools to assess the coronary microcirculation? Circulation 1996;96:719-24.Google Scholar
  20. 20.
    Cerqueira MD, Nguyen P, Staehr P, Underwood SR, Iskandrian AE, On Behalf of the ADVANCE-MPI Trial Investigators. 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. J Am Coll Cardiol CV Imaging 2008;1:307-16.Google Scholar
  21. 21.
    Xu Y, Hayes S, Ali I, Ruddy TD, Wells RG, Berman DS, et al. Automatic and visual reproducibility of perfusion and function measures for myocardial perfusion SPECT. J Nucl Cardiol 2010;17:1050-7.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Prenner BM, Bukofzer S, Behm S, Feaheny K, McNutt BE. A randomized, double-blind, placebo-controlled study assessing the safety and tolerability of regadenoson in subjects with asthma or chronic obstructive pulmonary disease. J Nucl Cardiol 2012;19:681-92.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Ananthrasubramaniam K, Weiss R, McNutt B, Klauke B, Feaheny K, Bukofzer S. A randomized, double-blind, placebo-controlled study of the safety and tolerance of regadenoson in subjects with stage 3 or 4 chronic kidney disease. J Nucl Cardiol 2012;19:319-29.CrossRefGoogle Scholar
  24. 24.
    Rosenblatt J, Mooney D, Dunn T, Cohen M. Asystole following regadenoson infusion in stable outpatients. J Nucl Cardiol 2014. doi: 10.1007/s12350-014-9898-0.

Copyright information

© American Society of Nuclear Cardiology 2014

Authors and Affiliations

  • John J. Mahmarian
    • 1
  • Leif E. Peterson
    • 2
  • Jiaqiong Xu
    • 2
  • Manuel D. Cerqueira
    • 3
  • Ami E. Iskandrian
    • 4
  • Timothy M. Bateman
    • 5
  • Gregory S. Thomas
    • 6
  • Faisal Nabi
    • 1
  1. 1.Houston Methodist DeBakey Heart & Vascular CenterHouston MethodistHoustonUSA
  2. 2.Houston Methodist Research InstituteHouston MethodistHoustonUSA
  3. 3.Cleveland ClinicClevelandUSA
  4. 4.University of Alabama at BirminghamBirminghamUSA
  5. 5.Mid America Heart Institute of Saint Luke’s HospitalKansas CityUSA
  6. 6.Long Beach Memorial Medical Center and University of California, IrvineOrangeUSA

Personalised recommendations