Journal of Nuclear Cardiology

, Volume 14, Issue 5, pp 645–658 | Cite as

Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: Results of the ADVANCE phase 3 multicenter international trial

  • Ami E. IskandrianEmail author
  • Timothy M. Bateman
  • Luiz Belardinelli
  • Brent Blackburn
  • Manuel D. Cerqueira
  • Robert C. Hendel
  • Hsiao Lieu
  • John J. Mahmarian
  • Ann Olmsted
  • S. Richard Underwood
  • João Vitola
  • Whedy Wang
  • the ADVANCE MPI Investigators
Original Articles



Earlier phase 1 and 2 studies have shown that regadenoson has desirable features as a stress agent for myocardial perfusion imaging.

Methods and Results

This multicenter, double-blinded phase 3 trial involved 784 patients at 54 sites. Each patient underwent 2 sets of gated single photon emission computed tomography myocardial perfusion imaging studies: an initial qualifying study with adenosine and a subsequent randomized study with either regadenoson (2/3 of patients) or adenosine. Regadenoson was administered as a rapid bolus (<10 seconds) of 400 μg. The primary endpoint was to demonstrate noninferiority by showing that the difference in the strength of agreement in detecting reversible defects, based on blinded reading, between sequential adenosine-regadenoson images and adenosine-adenosine images, lay above a prespecified noninferiority margin. Other prospectively defined safety and tolerability comparisons and supporting analyses were also performed. The average agreement rate based on the median of 3 independent blinded readers was 0.63±0.03 for regadenoson-adenosine and 0.64±0.04 for adenosine-adenosine—a 1% absolute difference with the lower limit of the 95% confidence interval lying above the prespecified noninferiority margin. Side-by-side interpretation of regadenoson and adenosine images provided comparable results for detecting reversible defects. The peak increase in heart rate was greater with regadenoson than adenosine, but the blood pressure nadir was similar. A summed symptom score of flushing, chest pain, and dyspnea was less with regadenoson than adenosine (P=.013).


This phase 3 trial shows that regadenoson provides diagnostic information comparable to a standard adenosine infusion. There were no serious drug-related side effects, and regadenoson was better tolerated than adenosine.

Key Words

Adenosine regadenoson single photon emission computed tomography stress imaging coronary artery disease ischemia perfusion imaging 


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Copyright information

© American Society of Nuclear Cardiology 2007

Authors and Affiliations

  • Ami E. Iskandrian
    • 1
    Email author
  • Timothy M. Bateman
    • 2
  • Luiz Belardinelli
    • 3
  • Brent Blackburn
    • 3
  • Manuel D. Cerqueira
    • 4
  • Robert C. Hendel
    • 5
  • Hsiao Lieu
    • 3
  • John J. Mahmarian
    • 6
  • Ann Olmsted
    • 3
  • S. Richard Underwood
    • 7
  • João Vitola
    • 8
  • Whedy Wang
    • 3
  • the ADVANCE MPI Investigators
  1. 1.Department of Medicine and RadiologyUniversity of Alabama at BirminghamBirmingham
  2. 2.Cardiovascular ConsultantsKansas CityUSA
  3. 3.CV TherapeuticsPalo AltoUSA
  4. 4.Cleveland ClinicClevelandUSA
  5. 5.Midwest Heart SpecialistsFox River GroveUSA
  6. 6.The Methodist DeBakey Heart Center at The Methodist HospitalHoustonUSA
  7. 7.Imperial College LondonRoyal Brompton HospitalLondonEngland
  8. 8.Quanta Medicina NuclearFederal University Medical SchoolCuritibaBrazil

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