Budesonide/Formoterol for Asthma Shows Cardiovascular Safety

ORLANDO – Budesonide/formoterol pressurized metered-dose inhaler demonstrated similar cardiovascular safety to that of budesonide treatment alone in a study of 742 black adolescents and adults with moderate to severe asthma.

There has been concern that regular long-acting beta₂-adrenergic agonist (LABA) therapy may increase the risk of mortality, including that from cardiac adverse events. An analysis of asthma trials suggested that formoterol does not increase cardiac-related serious adverse events or cardiac-related deaths (Eur. Respir. J. 2009;33:21-32).

And a recent study showed that budesonide/formoterol pressurized metered-dose inhaler (BUD/FM pMDI) was well tolerated and more effective for preventing exacerbations, compared with monotherapy BUD pMDI, in a black patient population (Am. J. Respir. Crit. Care Med. 2011;183:A1294).

However, data have been limited on the cardiovascular safety of combination inhaled corticosteroids (ICSs) and LABAs in specific racial/ethnic patient populations with asthma, Dr. Kathy L. Lampl of AstraZeneca and her associates reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In a randomized, double-blind, parallel-group, multicenter, 52-week study, 742 patients with moderate to severe persistent asthma who self-reported their race as black were randomized 1:1 to receive BUD/FM pMDI (160/4.5 mcg × 2 inhalations, total 320/9 mcg) or BUD pMDI (160 mcg × 2 inhalations, total 320 mcg) twice daily. Twelve-lead electrocardiograms were obtained before the morning dose of study medication in all patients at visits two through nine.

All patients were on a consistent daily medium to high dose of ICS either taken alone or as combination therapy with a LABA for 30 days or longer before screening.

Changes from baseline to treatment maximum for BUD/FM vs. BUD were similar for heart rate (9.87 vs. 9.04 beats/minute) and QT interval corrected for heart rate, with QTc 18.46 vs. 18.18 msec (Bazett’s correction) and QTc 13.47 vs. 14.73 msec (Fridericia’s correction), but lower for the uncorrected QT interval, 15.59 vs. 19.12 msec (unadjusted P = .002).

The proportion of patients with a heart rate greater than 100 beats/min or an increase of 20 or more beats per minute were 11.4% for BUD/FM and 8.5% for BUD, which is consistent with known effects of beta₂-adrenergic agonists, Dr. Lampl and her associates said.

Cardiac events were infrequent, and all were considered nonserious. Cardiac adverse events occurred in six patients (1.6%) in the BUD/FM pMDI group, including cardiac conduction disorders (one patient, 0.3%), ischemic coronary artery disorders (one patient, 0.3%), rate and rhythm disorders (two patients, 0.5%), supraventricular arrhythmias (two patients, 0.5%), and ventricular arrhythmias and cardiac arrest (one patient, 0.3%). Four patients (1.1%) in the BUD pMDI group experienced a cardiac adverse event, including cardiac conduction disorders (two patients, 0.5%), cardiac signs and symptoms (one patient, 0.3%), and noninfectious pericarditis (one patient, 0.3%).

"Overall, the results of this study further support the long-term tolerability of BUD/FM pMDI in African-American adolescents and adults with moderate to severe asthma not adequately controlled on an ICS alone," Dr. Lampl and her associates concluded.

Dr. Lampl is a paid employee of AstraZeneca, which funded the study.

ORLANDO – Budesonide/formoterol pressurized metered-dose inhaler demonstrated similar cardiovascular safety to that of budesonide treatment alone in a study of 742 black adolescents and adults with moderate to severe asthma.

There has been concern that regular long-acting beta₂-adrenergic agonist (LABA) therapy may increase the risk of mortality, including that from cardiac adverse events. An analysis of asthma trials suggested that formoterol does not increase cardiac-related serious adverse events or cardiac-related deaths (Eur. Respir. J. 2009;33:21-32).

And a recent study showed that budesonide/formoterol pressurized metered-dose inhaler (BUD/FM pMDI) was well tolerated and more effective for preventing exacerbations, compared with monotherapy BUD pMDI, in a black patient population (Am. J. Respir. Crit. Care Med. 2011;183:A1294).

However, data have been limited on the cardiovascular safety of combination inhaled corticosteroids (ICSs) and LABAs in specific racial/ethnic patient populations with asthma, Dr. Kathy L. Lampl of AstraZeneca and her associates reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In a randomized, double-blind, parallel-group, multicenter, 52-week study, 742 patients with moderate to severe persistent asthma who self-reported their race as black were randomized 1:1 to receive BUD/FM pMDI (160/4.5 mcg × 2 inhalations, total 320/9 mcg) or BUD pMDI (160 mcg × 2 inhalations, total 320 mcg) twice daily. Twelve-lead electrocardiograms were obtained before the morning dose of study medication in all patients at visits two through nine.

All patients were on a consistent daily medium to high dose of ICS either taken alone or as combination therapy with a LABA for 30 days or longer before screening.

Changes from baseline to treatment maximum for BUD/FM vs. BUD were similar for heart rate (9.87 vs. 9.04 beats/minute) and QT interval corrected for heart rate, with QTc 18.46 vs. 18.18 msec (Bazett’s correction) and QTc 13.47 vs. 14.73 msec (Fridericia’s correction), but lower for the uncorrected QT interval, 15.59 vs. 19.12 msec (unadjusted P = .002).

The proportion of patients with a heart rate greater than 100 beats/min or an increase of 20 or more beats per minute were 11.4% for BUD/FM and 8.5% for BUD, which is consistent with known effects of beta₂-adrenergic agonists, Dr. Lampl and her associates said.

Cardiac events were infrequent, and all were considered nonserious. Cardiac adverse events occurred in six patients (1.6%) in the BUD/FM pMDI group, including cardiac conduction disorders (one patient, 0.3%), ischemic coronary artery disorders (one patient, 0.3%), rate and rhythm disorders (two patients, 0.5%), supraventricular arrhythmias (two patients, 0.5%), and ventricular arrhythmias and cardiac arrest (one patient, 0.3%). Four patients (1.1%) in the BUD pMDI group experienced a cardiac adverse event, including cardiac conduction disorders (two patients, 0.5%), cardiac signs and symptoms (one patient, 0.3%), and noninfectious pericarditis (one patient, 0.3%).

"Overall, the results of this study further support the long-term tolerability of BUD/FM pMDI in African-American adolescents and adults with moderate to severe asthma not adequately controlled on an ICS alone," Dr. Lampl and her associates concluded.

Dr. Lampl is a paid employee of AstraZeneca, which funded the study.

ORLANDO – Budesonide/formoterol pressurized metered-dose inhaler demonstrated similar cardiovascular safety to that of budesonide treatment alone in a study of 742 black adolescents and adults with moderate to severe asthma.

There has been concern that regular long-acting beta₂-adrenergic agonist (LABA) therapy may increase the risk of mortality, including that from cardiac adverse events. An analysis of asthma trials suggested that formoterol does not increase cardiac-related serious adverse events or cardiac-related deaths (Eur. Respir. J. 2009;33:21-32).

And a recent study showed that budesonide/formoterol pressurized metered-dose inhaler (BUD/FM pMDI) was well tolerated and more effective for preventing exacerbations, compared with monotherapy BUD pMDI, in a black patient population (Am. J. Respir. Crit. Care Med. 2011;183:A1294).

However, data have been limited on the cardiovascular safety of combination inhaled corticosteroids (ICSs) and LABAs in specific racial/ethnic patient populations with asthma, Dr. Kathy L. Lampl of AstraZeneca and her associates reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In a randomized, double-blind, parallel-group, multicenter, 52-week study, 742 patients with moderate to severe persistent asthma who self-reported their race as black were randomized 1:1 to receive BUD/FM pMDI (160/4.5 mcg × 2 inhalations, total 320/9 mcg) or BUD pMDI (160 mcg × 2 inhalations, total 320 mcg) twice daily. Twelve-lead electrocardiograms were obtained before the morning dose of study medication in all patients at visits two through nine.

All patients were on a consistent daily medium to high dose of ICS either taken alone or as combination therapy with a LABA for 30 days or longer before screening.

Changes from baseline to treatment maximum for BUD/FM vs. BUD were similar for heart rate (9.87 vs. 9.04 beats/minute) and QT interval corrected for heart rate, with QTc 18.46 vs. 18.18 msec (Bazett’s correction) and QTc 13.47 vs. 14.73 msec (Fridericia’s correction), but lower for the uncorrected QT interval, 15.59 vs. 19.12 msec (unadjusted P = .002).

The proportion of patients with a heart rate greater than 100 beats/min or an increase of 20 or more beats per minute were 11.4% for BUD/FM and 8.5% for BUD, which is consistent with known effects of beta₂-adrenergic agonists, Dr. Lampl and her associates said.

Cardiac events were infrequent, and all were considered nonserious. Cardiac adverse events occurred in six patients (1.6%) in the BUD/FM pMDI group, including cardiac conduction disorders (one patient, 0.3%), ischemic coronary artery disorders (one patient, 0.3%), rate and rhythm disorders (two patients, 0.5%), supraventricular arrhythmias (two patients, 0.5%), and ventricular arrhythmias and cardiac arrest (one patient, 0.3%). Four patients (1.1%) in the BUD pMDI group experienced a cardiac adverse event, including cardiac conduction disorders (two patients, 0.5%), cardiac signs and symptoms (one patient, 0.3%), and noninfectious pericarditis (one patient, 0.3%).

"Overall, the results of this study further support the long-term tolerability of BUD/FM pMDI in African-American adolescents and adults with moderate to severe asthma not adequately controlled on an ICS alone," Dr. Lampl and her associates concluded.

Dr. Lampl is a paid employee of AstraZeneca, which funded the study.