ASNC: Regadenoson safe in patients with asthma, COPD
PHILADELPHIA—The use of the pharmacologic stressor regadenoson (Lexiscan, Astellas Pharma) in patients with asthma and chronic obstructive pulmonary disease (COPD) is safe regarding events of bronchospasm, according to a late-breaking clinical trial of more than 1,000 patients presented at the 2010 annual meeting of the American Society of Nuclear Cardiology (ASNC).
Patients with reactive airways are at risk for adenosine-induced bronchoconstriction via the A2B and/or A3 adenosine receptors, according to Bruce M. Prenner, MD, from Allergy Associates Medical Group in San Diego, who presented the study on behalf of approximately 50 co-investigators.
Unlike other stressor agents, regadenoson has greater selectivity for A2A receptors, which theoretically should reduce common adverse events associated with non-specific A2A receptor stressors such as adenosine and dipyridamole, which are contraindicated in patients with reactive airways who are at risk for bronchospasms.
Prenner and colleagues evaluated regadenoson in multicenter, randomized double-blind, placebo-controlled study at a 2:1 ratio of regadenoson to placebo. Researchers monitored respiratory function parameters for two hours post-injection and adverse events up to one day post-injection.
The study population consisted of 532 patients with asthma (356 regadenoson) and 467 with COPD (316 regadenoson). The mean age of subjects was 52. More females had asthma, while more males had COPD. The distribution in severity among those with asthma and COPD was similar.
Among patients with asthma, 1.1 percent of those who received the stressor and 2.9 percent of those who received placebo had a greater than 15 percent decrease in forced expiratory volume in one second (FEV1) from baseline to two hours post-injection (primary endpoint). The difference was not significant.
Among patients with COPD, 4.2 percent and 5.4 percent of patients receiving regadenoson and placebo, respectively, exhibited the primary endpoint. The difference was not significant.
Selected respiratory adverse events (secondary endpoint), including wheezing, dyspnea, dyspnea exertional, obstructive airways disorder and tachypnea, were significantly more common with regadenoson in those with asthma (12 vs. 2.3 percent) and COPD (19 vs. 4 percent). The differences were significant in both patient groups.
Prenner said the differences were driven by dyspnea, a side effect of A2A agonists.
The use of short-acting bronchodilators within one day of injection for selected respiratory adverse events was similar in the regadenoson and placebo arms of both patient groups.
Despite the higher rate of adverse events in the regadenoson arms, Prenner said there were no clinically meaningful differences between treatments in pulmonary function tests in either patient group. "The adverse event profile was similar to that observed in previous regadenoson trials in non-asthmatic/COPD patients," he said.
"The important message is that most patients experiencing adverse events did not need treatment and they recovered very quickly," he said.
Of the six serious adverse events (all with regadenoson), three were considered treatment-related (complete atrioventricular block, severe bradycardia and EKG change).
Brenner concluded that there was a small incidence of adverse events associated with regadenoson. Additionally, the overall incidence of respiratory adverse events was statistically significantly higher with regadenoson in both the asthma and COPD groups, but did not result in greater use of short-acting beta agonists during these events.
"This information should be useful in the selection of regadenoson as a pharmacological stress agent in these important patient populations," he said.
Patients with reactive airways are at risk for adenosine-induced bronchoconstriction via the A2B and/or A3 adenosine receptors, according to Bruce M. Prenner, MD, from Allergy Associates Medical Group in San Diego, who presented the study on behalf of approximately 50 co-investigators.
Unlike other stressor agents, regadenoson has greater selectivity for A2A receptors, which theoretically should reduce common adverse events associated with non-specific A2A receptor stressors such as adenosine and dipyridamole, which are contraindicated in patients with reactive airways who are at risk for bronchospasms.
Prenner and colleagues evaluated regadenoson in multicenter, randomized double-blind, placebo-controlled study at a 2:1 ratio of regadenoson to placebo. Researchers monitored respiratory function parameters for two hours post-injection and adverse events up to one day post-injection.
The study population consisted of 532 patients with asthma (356 regadenoson) and 467 with COPD (316 regadenoson). The mean age of subjects was 52. More females had asthma, while more males had COPD. The distribution in severity among those with asthma and COPD was similar.
Among patients with asthma, 1.1 percent of those who received the stressor and 2.9 percent of those who received placebo had a greater than 15 percent decrease in forced expiratory volume in one second (FEV1) from baseline to two hours post-injection (primary endpoint). The difference was not significant.
Among patients with COPD, 4.2 percent and 5.4 percent of patients receiving regadenoson and placebo, respectively, exhibited the primary endpoint. The difference was not significant.
Selected respiratory adverse events (secondary endpoint), including wheezing, dyspnea, dyspnea exertional, obstructive airways disorder and tachypnea, were significantly more common with regadenoson in those with asthma (12 vs. 2.3 percent) and COPD (19 vs. 4 percent). The differences were significant in both patient groups.
Prenner said the differences were driven by dyspnea, a side effect of A2A agonists.
The use of short-acting bronchodilators within one day of injection for selected respiratory adverse events was similar in the regadenoson and placebo arms of both patient groups.
Despite the higher rate of adverse events in the regadenoson arms, Prenner said there were no clinically meaningful differences between treatments in pulmonary function tests in either patient group. "The adverse event profile was similar to that observed in previous regadenoson trials in non-asthmatic/COPD patients," he said.
"The important message is that most patients experiencing adverse events did not need treatment and they recovered very quickly," he said.
Of the six serious adverse events (all with regadenoson), three were considered treatment-related (complete atrioventricular block, severe bradycardia and EKG change).
Brenner concluded that there was a small incidence of adverse events associated with regadenoson. Additionally, the overall incidence of respiratory adverse events was statistically significantly higher with regadenoson in both the asthma and COPD groups, but did not result in greater use of short-acting beta agonists during these events.
"This information should be useful in the selection of regadenoson as a pharmacological stress agent in these important patient populations," he said.