Effect of body mass index on the efficacy, side effect profile, and plasma concentration of fixed-dose regadenoson for myocardial perfusion imaging
- 220 Downloads
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.
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.
KeywordsMyocardial perfusion imaging regadenoson body mass index efficacy side effects tolerability
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.
- 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
- 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
- 11.Food and Drug Administration. Population pharmacokinetics. US Department of Health and Human Services Guidance for Industry 1999;1-31.Google Scholar
- 12.Beal S, Sheiner L, Oeckmann AJE. Icon Development Solutions. NONMEM Users Guides 2006.Google Scholar
- 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
- 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