Skip to main content
SpringerLink
Log in

The safety and tolerability of regadenoson in patients with end-stage renal disease: The first prospective evaluation

  • Original Article
  • Published:
Journal of Nuclear Cardiology Aims and scope

Abstract

Background

There has not been any prospective evaluation of the safety and tolerability of regadenoson (REG)-stress in patients with end-stage renal disease (ESRD).

Methods

From the pooled database of two identically designed randomized, double-blinded, placebo-controlled clinical trials, ASSUAGE and ASSUAGE-CKD (IV-aminophylline vs placebo following REG-stress), we extracted the placebo-treated subjects to form 2 study groups: ESRD (dialysis or GFR < 15 mL/minute/1.73 m2) and control (GFR ≥ 30). The incidence of REG adverse effects and the hemodynamic and ECG responses to REG-stress were compared.

Results

We identified 146 ESRD subjects and 97 controls. There was no significant difference in the incidence of the composite of any REG adverse effect [ESRD 108 (74%) vs control 73 (75%), P = .82]. ESRD patients seem to have excess incidences of diarrhea [42 (29%) vs 14 (14%), P = .009] and fewer events of dizziness [28 (19%) vs 43 (44%), P < .001]. There were no serious adverse events in either group. There was no significant difference in the incidence of ST-segment deviation, tachyarrhythmias, atrioventricular block, or hypotension.

Conclusion

This is the first prospective study to confirm the safety and tolerability of REG in patients with ESRD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. 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 

  2. 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 

  3. Garnock-Jones KP, Curran MP. Regadenoson. Am J Cardiovasc Drugs 2010;10:65-71.

    Article  PubMed  CAS  Google Scholar 

  4. Hendel RC, Bateman TM, Cerqueira MD, Iskandrian AE, Leppo JA, Blackburn B, et al. Initial clinical experience with regadenoson, a novel selective A(2A) 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 

  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. JACC Cardiovasc Imaging 2009;2:959-68.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  7. 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 

  8. 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 

  9. 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 

  10. Ananthasubramaniam 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.

    Article  PubMed  Google Scholar 

  11. Palani G, Husain Z, Salinas RC, Karthikeyan V, Karthikeyan AS, Ananthasubramaniam K. Safety of regadenoson as a pharmacologic stress agent for myocardial perfusion imaging in chronic kidney disease patients not on hemodialysis. J Nucl Cardiol 2011;18:605-11.

    Article  PubMed  Google Scholar 

  12. Aljaroudi W, Hermann D, Hage F, Heo J, Iskandrian AE. Safety of regadenoson in patients with end-stage renal disease. Am J Cardiol 2010;105:133-5.

    Article  PubMed  CAS  Google Scholar 

  13. Venkataraman R, Hage FG, Dorfman T, Heo J, Aqel RA, de Mattos AM, et al. Role of myocardial perfusion imaging in patients with end-stage renal disease undergoing coronary angiography. Am J Cardiol 2008;102:1451-6.

    Article  PubMed  Google Scholar 

  14. Doukky R. Morales Demori R, Jain S, Kiriakos R, Mwansa V, Calvin JE. Attenuation of the side effect profile of regadenoson: a randomized double-blinded placebo-controlled study with aminophylline in patients undergoing myocardial perfusion imaging. “The ASSUAGE trial”. J Nucl Cardiol 2012;19:448-57.

    Article  PubMed  Google Scholar 

  15. Doukky R, Rangel MO, Dick R, Wassouf M, Alqaid A, Margeta B. Attenuation of the side effect profile of regadenoson: a randomized double-blind placebo-controlled study with aminophylline in patients undergoing myocardial perfusion imaging and have severe chronic kidney disease. “The ASSUAGE-CKD trial”. Int J Cardiovasc Imaging 2012 (in press).

  16. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41.

    Article  PubMed  CAS  Google Scholar 

  17. Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol 1997;32:920-4.

    Article  PubMed  CAS  Google Scholar 

  18. Henzlova MJ, Cerqueira MD, Mahmarian JJ, Yao SS. Stress protocols and tracers. J Nucl Cardiol 2006;13:e80-90.

    Article  PubMed  Google Scholar 

  19. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 2002;105:539-42.

    Article  PubMed  Google Scholar 

  20. 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 

  21. 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 

  22. 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 

  23. Laighold S, Druz R. Initial clinical experience with a selective A2A receptor agonist, regadenoson, in a patient with end-stage renal disease on hemodialysis. J Nucl Cardiol 2009;16:478-80.

    Article  PubMed  Google Scholar 

  24. Kimura K, Tabei K, Asano Y, Hosoda S. Cardiac arrhythmias in hemodialysis patients. A study of incidence and contributory factors. Nephron 1989;53:201-7.

    Article  PubMed  CAS  Google Scholar 

  25. Abe S, Yoshizawa M, Nakanishi N, Yazawa T, Yokota K, Honda M, et al. Electrocardiographic abnormalities in patients receiving hemodialysis. Am Heart J 1996;131:1137-44.

    Article  PubMed  CAS  Google Scholar 

  26. Bozbas H, Atar I, Yildirir A, Ozgul A, Uyar M, Ozdemir N, et al. Prevalence and predictors of arrhythmia in end stage renal disease patients on hemodialysis. Ren Fail 2007;29:331-9.

    Article  PubMed  Google Scholar 

  27. Palmer Alves T, Lewis J. Racial differences in chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the United States: A social and economic dilemma. Clin Nephrol 2010;2010:S72-7.

    Google Scholar 

Download references

Conflicts of interest

Rami Doukky received research support from Astellas Pharma, none of which was used to fund this investigation. No conflicts of interest to be reported by other authors.

Author information

Authors and Affiliations

  1. Section of Cardiology, Rush University Medical Center, 1653 W. Congress Pkwy, Chicago, IL, 60612, USA

    Rami Doukky MD, MSc, FACC, FASNC, Maria Octavia Rangel MD, Marwan Wassouf MD, Rizcallah Dick MD, Ammar Alqaid MD & Raysa Morales Demori MD

Authors
  1. Rami Doukky MD, MSc, FACC, FASNC
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Octavia Rangel MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marwan Wassouf MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rizcallah Dick MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ammar Alqaid MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Raysa Morales Demori MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rami Doukky MD, MSc, FACC, FASNC.

Additional information

Rami Doukky and Maria Octavia Rangel contributed equally to the manuscript and should be treated as co-first authors.

See related editorial, doi: 10.1007/s12350-012-9658-y

Rights and permissions

Reprints and permissions

About this article

Cite this article

Doukky, R., Rangel, M.O., Wassouf, M. et al. The safety and tolerability of regadenoson in patients with end-stage renal disease: The first prospective evaluation. J. Nucl. Cardiol. 20, 205–213 (2013). https://doi.org/10.1007/s12350-012-9654-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12350-012-9654-2

Keywords

Search

Navigation