Background: An increase in serious adverse events with both regular formoterol and regular salmeterol in chronic asthma has been demonstrated in previous Cochrane reviews.
Objectives: We set out to compare the risks of mortality and non-fatal serious adverse events in trials which have randomised patients with chronic asthma to regular formoterol versus regular salmeterol.
Search strategy: Trials were identified using the Cochrane Airways Group Specialised Register of trials. Manufacturers' web sites of clinical trial registers were checked for unpublished trial data and Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol were also checked. The date of the most recent search was January 2009.
Selection criteria: Controlled parallel design clinical trials on patients of any age and severity of asthma were included if they randomised patients to treatment with regular formoterol versus regular salmeterol (without randomised inhaled corticosteroids), and were of at least 12 weeks duration.
Data collection and analysis: Two authors independently selected trials for inclusion in the review and extracted outcome data. Unpublished data on mortality and serious adverse events were sought from the sponsors and authors.
Main results: Four studies were included in the review (involving 1116 adults and 156 children). All studies were open label and recruited patients who were already taking inhaled corticosteroids for their asthma, and all studies contributed data on serious adverse events. All studies compared formoterol 12 mug versus salmeterol 50 mug twice daily. The adult studies were all comparing Foradil Aerolizer with Serevent Diskus, and the children's study compared Oxis Turbohaler to Serevent Accuhaler. There was only one death in an adult (which was unrelated to asthma), and none in children, and there were no significant differences in non-fatal serious adverse events comparing formoterol to salmeterol in adults (Peto OR 0.77; 95% CI 0.46 to 1.28), or children (Peto OR 0.95; 95% CI 0.06 to 15.33). Over a six month period in studies involving adults that contributed to this analysis the percentage with serious adverse events were 5.1% for formoterol and 6.4% for salmeterol; and over a 3 month period the percentage of children with serious adverse events were 1.3% for formoterol, and 1.3% for salmeterol.
Authors' conclusions: Four studies have been identified comparing regular formoterol to regular salmeterol (without randomised inhaled corticosteroids, but all subjects were on regular background inhaled corticosteroids). The events were infrequent and consequently too few patients have been studied to allow any firm conclusions to be drawn about the relative safety of formoterol and salmeterol. Asthma-related serious adverse events were rare, and there were no reported asthma-related deaths.