title: Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial.
abstract: BACKGROUND
  Earlier phase 1 and 2 studies have shown that regadenoson has desirable features as a stress agent for myocardial perfusion imaging.
  
  
  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 mug. 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL 35294-0006, USA. aiskand@uab.edu
authors.forename: Ami E
authors.initials: AE
authors.lastname: Iskandrian
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Bateman
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
authors.forename: Brent
authors.initials: B
authors.lastname: Blackburn
authors.forename: Manuel D
authors.initials: MD
authors.lastname: Cerqueira
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hendel
authors.forename: Hsiao
authors.initials: H
authors.lastname: Lieu
authors.forename: John J
authors.initials: JJ
authors.lastname: Mahmarian
authors.forename: Ann
authors.initials: A
authors.lastname: Olmsted
authors.forename: S Richard
authors.initials: SR
authors.lastname: Underwood
authors.forename: João
authors.initials: J
authors.lastname: Vitola
authors.forename: Whedy
authors.initials: W
authors.lastname: Wang
mesh_terms: D000241:Adenosine / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005080:Exercise Test / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011687:Purines / Q000009:adverse effects; D011720:Pyrazoles / Q000009:adverse effects; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013382:Subtraction Technique; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014665:Vasodilator Agents / Q000009:adverse effects; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging*