The safety of long-acting beta(2)-agonist (LABA) treatment in
asthma has been questioned following reported increased respiratory deaths when
salmeterol was added to usual
pharmacotherapy. The aim of this study was to examine whether
asthma, cardiac or all-cause mortality and morbidity were increased with
formoterol use. The analysis included all AstraZeneca randomised controlled parallel-group
asthma trials of 3-12-months duration involving
formoterol. Risks associated with
formoterol use compared with non-LABA treatment, overall and in combination with inhaled
corticosteroids (ICS), were assessed using an intention-to-treat analysis of the rates and rate ratios of deaths and serious adverse events (SAEs). The main objective of this study was to compare
asthma-related mortality in patients using
formoterol and those not using
formoterol. There were eight
asthma-related deaths (0.34 per 1,000 person-yrs) among 49,906
formoterol-randomised patients (92% using ICS), and two (0.22 per 1,000 person-yrs) among 18,098 patients (83% using ICS) not randomised to
formoterol, which was nonsignificant.
Asthma-related SAEs (>90% of which were hospitalisations) were significantly fewer among
formoterol-randomised patients (0.75 versus 1.10%). There was no increase in
asthma-related SAEs with increased daily doses of
formoterol (9, 18 or 36 microg). There was no significant difference in cardiac mortality or noncardiac nonasthma-related mortality in
formoterol-randomised compared to non-LABA-treated patients. All-cause mortality was similar. In the data set in which all subjects were prescribed ICS at baseline, there were seven
asthma-related deaths (0.32 per 1,000 person-yrs) among 46,003
formoterol-randomised patients and one (0.14 per 1,000 person-yrs) among 13,905 patients not randomised to
formoterol, which was also nonsignificant. There were few
asthma-related or cardiac-related deaths among patients randomised to
formoterol, and all differences were nonsignificant compared with non-long-acting beta(2)-agonist-randomised patients. However, despite data on >68,000 patients, the power was insufficient to conclude that there was no increased mortality with
formoterol. Cardiac-related serious adverse events were not increased, and
asthma-related serious adverse events were significantly reduced with
formoterol.