Journal of Nuclear Cardiology

, Volume 18, Issue 4, pp 620–627 | Cite as

Effect of body mass index on the efficacy, side effect profile, and plasma concentration of fixed-dose regadenoson for myocardial perfusion imaging

  • Eliana Reyes
  • Peter Staehr
  • Ann Olmsted
  • Dewan Zeng
  • Brent Blackburn
  • Manuel D. Cerqueira
  • S. Richard Underwood
Original Article

Abstract

Background

There are limited data on the effect of body mass index (BMI) on the actions of fixed-dose regadenoson. The purpose of this study was to determine the effect of BMI on the efficacy, side effects, and plasma concentration of regadenoson for Myocardial Perfusion Imaging (MPI).

Methods and Results

The study included 2,015 subjects from the ADVANCE MPI trials. Initial adenosine MPI was followed by randomization to regadenoson (400-μg bolus injection) or adenosine (6-minute infusion) MPI. Subjects were classified according to BMI into six categories from underweight (<20 kg/m2) to extremely obese (≥40 kg/m2). PK modeling was used to predict the effect of BMI on plasma regadenoson concentration (PRC). Adenosine-regadenoson agreement rates for the presence and extent of reversibility were similar across BMI categories (P > .05). The incidence of side effects was also similar across BMIs (P ≥ .06). Subjects were less likely to feel very or extremely uncomfortable after regadenoson vs adenosine in all groups with BMI ≥ 25 kg/m2, but this trend was not statistically significant in subjects with BMI 20-24 kg/m2 (P > .05). PRC was inversely related to BMI with 19% higher PRC in the underweight and 36% lower PRC in the extremely obese compared with a normal weight subject.

Conclusions

BMI does not alter the efficacy of regadenoson MPI despite lower PRC in high BMI subjects, or its side effect profile despite higher PRC in low BMI subjects. Regadenoson is better tolerated than adenosine but this benefit seems to lose statistical significance in subjects with BMI < 25 kg/m2.

Keywords

Myocardial perfusion imaging regadenoson body mass index efficacy side effects tolerability 

Notes

Acknowledgments

Authors would like to thank Dr Jerling, a former employee of CV Therapeutics, Inc., Justus Bingham and the Metrum Research Group for conducting the population PK modeling and simulation of regadenoson.

Conflict of interest

Drs Staehr, Olmsted, Zeng, and Blackburn are current employees of Gilead Sciences, Inc/CV Therapeutics, which provided funding for this study. Dr Cerqueira has served as Consultant and on the Speakers Bureau for CV Therapeutics, Inc, and currently serves as Consultant and on the Speakers Bureau for Astellas Pharma US. Professor Underwood has served as member of the publications committee of ADVANCE MPI trials, which were sponsored by CV Therapeutics, Inc. The other authors report no conflicts.

References

  1. 1.
    Klocke FJ, Baird MG, Lorell BH, Bateman TM, Messer JV, Berman DS, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging—executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). J Am Coll Cardiol 2003;42:1318–33.PubMedCrossRefGoogle Scholar
  2. 2.
    Loong CY, Anagnostopoulos C. Diagnosis of coronary artery disease by radionuclide myocardial perfusion imaging. Heart 2004;90:v2–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Botvinick EH, Dae MW. Dipyridamole perfusion scintigraphy. Semin Nucl Med 1991;21:242–65.PubMedCrossRefGoogle Scholar
  4. 4.
    Cerqueira MD, Verani MS, Schwaiger M, Heo J, Iskandrian AS. Safety profile of adenosine stress perfusion imaging: Results from the Adenoscan Multicenter Trial Registry. J Am Coll Cardiol 1994;23:384–9.PubMedCrossRefGoogle Scholar
  5. 5.
    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.PubMedCrossRefGoogle Scholar
  6. 6.
    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
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    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
  9. 9.
    Cerqueira MD, Nguyen P, Staehr P, Underwood SR, Iskandrian AE, 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. JACC Cardiovasc Imaging 2008;1:307–16.PubMedCrossRefGoogle Scholar
  10. 10.
    Gordi T, Blackburn B, Lieu H. Regadenoson pharmacokinetics and tolerability in subjects with impaired renal function. J Clin Pharmacol 2007;47:825–33.PubMedCrossRefGoogle Scholar
  11. 11.
    Food and Drug Administration. Population pharmacokinetics. US Department of Health and Human Services Guidance for Industry 1999;1-31.Google Scholar
  12. 12.
    Beal S, Sheiner L, Oeckmann AJE. Icon Development Solutions. NONMEM Users Guides 2006.Google Scholar
  13. 13.
    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;8:959-68.Google Scholar
  14. 14.
    Thomas GS, Prill NV, Majmundar H, Fabrizi RR, Thomas JJ, Hayashida C, et al. Treadmill exercise during adenosine infusion is safe, results in fewer adverse reactions, and improves myocardial perfusion image quality. J Nucl Cardiol 2000;7:439–46.PubMedCrossRefGoogle Scholar
  15. 15.
    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.PubMedCrossRefGoogle Scholar
  16. 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.PubMedGoogle Scholar

Copyright information

© American Society of Nuclear Cardiology 2011

Authors and Affiliations

  • Eliana Reyes
    • 1
    • 2
  • Peter Staehr
    • 3
  • Ann Olmsted
    • 3
  • Dewan Zeng
    • 3
  • Brent Blackburn
    • 3
    • 4
  • Manuel D. Cerqueira
    • 5
  • S. Richard Underwood
    • 1
    • 2
  1. 1.National Heart and Lung InstituteImperial College LondonLondonUnited Kingdom
  2. 2.Nuclear Medicine DepartmentRoyal Brompton HospitalLondonUnited Kingdom
  3. 3.Gilead Sciences, Inc/CV TherapeuticsFoster CityUSA
  4. 4.Rapidscan Pharma Solutions, IncLos AltosUSA
  5. 5.Heart and Vascular Institute and Imaging Institute, Cleveland ClinicClevelandUSA

Personalised recommendations