By Bruce Sylvester
CHICAGO -- April 2, 2008 -- Combined data from two phase 3 trials show that myocardial perfusion imaging using the investigative agent binodenoson, a selective adenosine A2A receptor agonist, detects myocardial ischaemia as effectively as imaging using adenosine, and with fewer and less adverse side effects.
The findings were presented here on March 31 at the 57th Annual Meeting of the American Academy of Cardiology (ACC 2008).
Imaging information on the extent and severity of ischaemia obtained using binodenoson during myocardial perfusion imaging (MPI) is the same as what is obtained with adenosine, said lead investigator James Udelson, MD, Acting Chief of Cardiology, Tufts Medical Center, Boston, Massachusetts.
However, consistent with binodenoson's receptor selectivity, this agent also resulted in a reduction in the incidence and intensity of adverse effects, he added.
For their analysis, Dr. Udelson and colleagues combined data from two multicentre studies in the United States -- VISION 302 (N=419) and VISION 305 (N=433). In both studies, subjects were randomised for pharmacologic stress testing using single photon emission computed tomography (SPECT) MPI.
Before testing, subjects were stratified by risk for coronary artery disease (CAD).
In the VISION 302 study, 374 subjects had low (6%), intermediate (45%), or high (24%) likelihood of CAD, and 26% had known CAD. In the VISION 305 trial, 391 subjects had low (5%), intermediate (44%), or high (10%) likelihood of CAD, and 41% had known CAD.
All subjects completed two double-blind MPI procedures within 7 days. In one procedure, they received an IV 1.5-µg/kg bolus of binodenoson plus a 6-minute placebo infusion. In the other procedure, they received an IV bolus placebo plus a 6-minute infusion of adenosine.
The rest-stress images were scored by blinded readers.
Efficacy was measured and compared based on the extent and severity of ischaemia, and expressed as summed difference scores (SDS). The mean paired difference between binodenoson images and adenosine images was well within SDS difference limits determined to indicate similar efficacy for purposes of imaging, the researchers said.
However, in the tolerability analysis no binodenoson subjects had second- or third-degree atrioventricular block compared with 3% of the adenosine subjects showing atrioventricular block.
In VISION 302, flushing was reduced by 36% among binodenoson subjects (P < .001), chest pain by 38% (P < .001), and shortness of breath by 18% (P = .007). Results in VISION 305 were similar to those in the 302 study, Dr. Udelson said.
Notably, 71% of the subjects said they preferred binodenoson. "The overall experience was preferred by patients to a much greater percentage among the binodenoson patients compared to the adenosine patients. So there was virtually identical clinical effect with much less side effects for binodenoson." Dr. Udelson added.
Funding for these studies was provided by King Pharmaceuticals.
[Presentation title: Efficacy and Safety of the Selective Adenosine A2A Receptor Agonist Binodenoson For Pharmacologic Stress: Results of a Phase 3, Randomized, Double-Blind, Risk-Stratified, Active-Controlled, Crossover Trial. Abstract 409-5]
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