Vasodilator-Induced Stress in Concordance With Adenosine - VISION 302 — Presented at SCAI-ACC i2 Summit/ACC 2008

Description:

The goal of this trial was to evaluate the safety and efficacy of the selective adenosine A2A receptor agonist binodenoson for pharmacologic stress in patients at risk or with known coronary artery disease (CAD).

Hypothesis:

Binodenoson is noninferior to adenosine as an agent for the demonstration of the magnitude of ischemia in pharmacologic stress tests in patients with suspected or known CAD.

Study Design

Study Design:

Patients Enrolled: 806
Mean Follow Up: 2-7 days
Mean Patient Age: 63.3 years
Female: 63

Patient Populations:

• Age ≥30 years
• Typical or atypical anginal chest pain
• Referred for clinical pharmacological stress myocardial perfusion imaging

Exclusions:

• Left ventricular ejection fraction <35%, or New York Heart Association class IV
• Very low test probability of CAD
• MI within 30 days, PCI or CABG within 3 years, unless new angina
• Contraindications for adenosine
• Pregnancy

Primary Endpoints:

Extent and severity of ischemia, expressed as SDS in a 17-segment model

Secondary Endpoints:

• Differences in fully automated, quantitative SDS
• Incidence of second- and third-degree AV block
• Incidence of side effects such as flushing, chest pain, and dyspnea
• Patient-related intensity of side effects
• Changes in blood pressure
• Changes in maximal heart rate achieved

Drug/Procedures Used:

Patients completed two double-blind, double-dummy myocardial perfusion imaging procedures in random order within 7 days: one with bolus 1.5 μg/kg binodenoson along with a 6-minute placebo infusion, and one with bolus placebo along with a 6-minute adenosine infusion at 140 µg/kg/min. 99mTc or 201Tl was given after 3 minutes of infusion for single-photon emission computed tomography (SPECT) imaging.

After 2-7 days, the patients crossed over, and received another scan with the other agent. Identical image protocols, camera, isotope, doses, acquisition times and time post-dose, time of day, and background antianginal medications held were maintained.

Principal Findings:

A total of 804 patients were enrolled in the VISION 302 trial, 402 to the binodenoson arm, and 404 to the adenosine arm: 94% had been referred for chest pain, 4% had prior myocardial infarction (MI), and 9% had prior coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). Patients were stratified based on pretest probability of having CAD: low risk 6%, intermediate risk 45%, high risk 24%, and known CAD 26%.

The mean paired summed difference scores (SDS) difference of binodenoson vs. adenosine images was -0.09 (95% confidence interval [CI] -0.44 to 0.27), well within the prespecified 1.5 SDS units for noninferiority. Difference in fully automated, quantitative SDS was -0.01 (95% CI, -0.29 to 0.27). There was about 61% concordance between the two agents, and 3% complete discordance.

Incidence of second- or third-degree atrioventricular (AV) block was 0% for binodenoson vs. 3% for adenosine (p = 0.004). Relative to adenosine, flushing was reduced with binodenoson (50% vs. 32%; p < 0.05), chest pain (61% vs. 38%; p < 0.05), and dyspnea (51% vs. 42%; p < 0.05). Patient-rated intensities of these events were lower during binodenoson than adenosine (p < 0.001). Changes in blood pressure were comparable between the two agents. Maximal changes in heart rate were higher with binodenoson than adenosine (25.3 vs. 22.5 bpm, p < 0.001).

Interpretation:

Binodenoson, a selective A2A receptor agonist, is as effective as adenosine, a nonselective agonist, as an agent for detection of ischemia in pharmacologic stress tests in patients with suspected or known CAD, with fewer and less intense side effects. Patients also tended to prefer binodenoson over adenosine in a blinded analysis. The cost-effectiveness of the two agents relative to each other is unclear.

References:

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. Presented by Dr. James E. Udelson at the SCAI-ACC i2 Summit/American College of Cardiology Annual Scientific Session, Chicago, IL, March/April 2008.

Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Cardiac Surgery and Heart Failure, Interventions and Coronary Artery Disease, Interventions and Imaging, Computed Tomography, Nuclear Imaging

Keywords: Myocardial Perfusion Imaging, Coronary Artery Disease, Myocardial Infarction, Tomography, Emission-Computed, Single-Photon, Blood Pressure, Dyspnea, Heart Rate, Percutaneous Coronary Intervention, Purinergic P1 Receptor Agonists, Probability, Confidence Intervals, Isotopes, Coronary Artery Bypass, Adenosine A2 Receptor Agonists, Exercise Test


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