Initial clinical experience with regadenoson, a novel selective A 2A agonist for pharmacologic stress single-photon emission computed tomography myocardial perfusion imaging

Objectives Regadenoson, a selective A 2A adenosine receptor agonist, was evaluated for tolerability and effectiveness as a pharmacological stress agent for detecting reversible myocardial hypoperfusion when combined with single-photon emission computed tomography (SPECT). Background Adenosine and dipyridamole are nonselective adenosine agonists currently used as pharmacologic stressors. Despite proven safety, these agents often cause undesirable side effects and require a continuous infusion. Methods This Phase II, multicenter, open-label trial was conducted in 36 patients who had demonstrated ischemia on a 6-min adenosine SPECT imaging study within the previous 2 to 46 days. Patients received regadenoson as a rapid intravenous bolus dose of 400 μg (n = 18) or 500 μg (n = 18). The radiopharmaceutical was then delivered within one minute. The SPECT images were acquired in a standard manner and uniformly processed at a central laboratory. Regadenoson and adenosine studies were presented in random order and interpreted blindly with a 17-segment model by three observers. Additionally, quantitative analysis was performed with 4D-MSPECT software (University of Michigan, Ann Arbor, Michigan). Results Overall agreement for the presence of reversible hypoperfusion was 86%. The 400-μg dose was better tolerated. Overall, regadenoson was well-tolerated; side effects (e.g., chest discomfort, flushing, dyspnea) were generally mild in severity and self-limiting. High-grade atrioventricular block and bronchospasm were not observed. Conclusions Regadenoson is well-tolerated and seems as effective as adenosine for detecting and quantifying the extent of hypoperfusion observed with SPECT perfusion imaging. Phase III clinical trials are now underway, given the promise of regadenoson’s reduced side effects and simplicity of bolus administration.