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The RegEx trial: a randomized, double-blind, placebo- and active-controlled pilot study combining regadenoson, a selective A2A adenosine agonist, with low-level exercise, in patients undergoing myocardial perfusion imaging

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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Although vasodilator stress myocardial perfusion imaging (MPI) is increasingly performed with exercise, adenosine A2A receptor agonists have not been studied with exercise.

Objectives

To determine the safety of administering regadenoson during exercise and, secondarily, to evaluate image quality, patient acceptance, and detection of perfusion defects.

Methods

Patients requiring pharmacologic MPI received a standard adenosine-supine protocol (AdenoSup, n = 60) and were then randomized (2:1) in a double-blind manner to low-level exercise with bolus intravenous injection of regadenoson (RegEx, n = 39) or placebo (PlcEx, n = 21).

Results

Adverse events occurred in 95%, 77%, and 33% of patients receiving AdenoSup, RegEx, and PlcEx, respectively. Peak heart rate was 13 beats per minute (bpm) and 21 bpm greater following RegEx compared to that following PlcEx and AdenoSup, respectively (P = .006 and <.001). Change from baseline in mean systolic blood pressure (SBP), change from baseline to nadir SBP, and percentage of patients with a decline in SBP by ≥20 mm Hg showed no important differences between RegEx and PlcEx. No occurrences of 2nd degree or higher AV block were observed following RegEx or PlcEx; one patient developed 2nd degree AV block following AdenoSup. The mean heart-to-liver and heart-to-gut ratios were improved on RegEx vs AdenoSup: 0.85 (0.34) vs 0.65 (0.26), P < .001 and 1.1 (0.36) vs 0.97 (0.34), P < .001, respectively. Compared to AdenoSup, 70% of patients felt RegEx was much or somewhat better.

Conclusions

Combining regadenoson with low-level exercise is feasible, well tolerated, and associated with fewer side effects compared to AdenoSup.

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Acknowledgments

The authors would like to acknowledge and thank Raymond Taillefer for his leadership of the nuclear core lab, Kim A. Williams, MD, Diwakar Jain, MD and Ronald G. Schwartz, MD, MS, independent interpreters of the nuclear images at the core lab and Mahesh P. Shah for his contribution of 7 subjects into the trial. We would also like to thank all the study research team and especially the subjects who graciously volunteered to participate in the study.

Drs Thomas, Thompson, Miyamoto, and Ip received research funding from CV Therapeutics. Dr Thomas additionally serves as a consultant to Astellas Pharma and is a past consultant to CV Therapeutics. He receives grant support from General Electric and Molecular Insights Pharmaceuticals and is on the speakers’ bureau for Astellas Pharma. Dr Mathur and Doug Milikien are current and former consultants to CV Therapeutics, respectively, and Dr Lieu is a former employee of CV Therapeutics.

Source of Financial Assistance: CV Therapeutics, Inc.

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Authors and Affiliations

  1. Cardiology Division, Mission Internal Medical Group, 26800 Crown Valley Pkwy, Suite 120, Mission Viejo, CA, 92691-6331, USA

    Gregory S. Thomas MD, MPH, FACC, FACP, FASNC, Michael I. Miyamoto MD, MS, FACC, Tze K. Ip MD, PhD & Deborah L. Rice RN

  2. Cardiology Division, University of California, Irvine, Irvine, CA, USA

    Gregory S. Thomas MD, MPH, FACC, FACP, FASNC

  3. Mid America Heart Institute, Kansas City, MO, USA

    Randall C. Thompson MD, FACC, FASNC

  4. Biostatistics, CV Therapeutics, Inc., Palo Alto, CA, USA

    Douglas Milikien MS

  5. Clinical Research, CV Therapeutics, Inc., Palo Alto, CA, USA

    Hsiao D. Lieu MD, FACC & Vandana S. Mathur MD, FASN

Authors
  1. Gregory S. Thomas MD, MPH, FACC, FACP, FASNC
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  2. Randall C. Thompson MD, FACC, FASNC
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  3. Michael I. Miyamoto MD, MS, FACC
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  4. Tze K. Ip MD, PhD
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  5. Deborah L. Rice RN
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  6. Douglas Milikien MS
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  7. Hsiao D. Lieu MD, FACC
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  8. Vandana S. Mathur MD, FASN
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Corresponding author

Correspondence to Gregory S. Thomas MD, MPH, FACC, FACP, FASNC.

Additional information

Presented, in part, at American College of Cardiology 56th Annual Scientific Session, New Orleans LA, March 25, 2007.

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Thomas, G.S., Thompson, R.C., Miyamoto, M.I. et al. The RegEx trial: a randomized, double-blind, placebo- and active-controlled pilot study combining regadenoson, a selective A2A adenosine agonist, with low-level exercise, in patients undergoing myocardial perfusion imaging. J. Nucl. Cardiol. 16, 63–72 (2009). https://doi.org/10.1007/s12350-008-9001-9

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  • DOI: https://doi.org/10.1007/s12350-008-9001-9

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