Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy.
BACKGROUND
There is concern that long-acting beta agonist (LABA) drugs may increase the risk of asthma mortality.


METHODS
A meta-analysis was conducted of asthma deaths in randomised controlled clinical trials from the GlaxoSmithKline database that compared salmeterol with a non-LABA comparator treatment in asthma. The Peto one-step method was used to determine the risk overall (all studies) and in derived datasets based on inhaled corticosteroid (ICS) use.


RESULTS
There were 35 asthma deaths in 215 studies with 106,575 subjects. Two studies (SMART and SNS) contributed 30/35 (86%) asthma deaths, the overall findings largely reflecting the characteristics of these studies. The odds ratio for risk of asthma mortality with salmeterol was 2.7 (95% CI 1.4 to 5.3). In 54 placebo controlled studies the risk of death from asthma in patients not prescribed ICS was 7.3 (95% CI 1.8 to 29.4). In 127 studies in which patients were prescribed ICS, the risk of asthma death was 2.1 (95% CI 0.6 to 7.9). In 63 studies in which patients were randomised to receive the combination salmeterol/fluticasone propionate inhaler or ICS, there were no asthma deaths among 22,600 patients.


CONCLUSIONS
Salmeterol monotherapy in asthma increases the risk of asthma mortality and this risk is reduced with concomitant ICS therapy. There is no evidence that combination salmeterol/fluticasone propionate therapy is associated with an increased risk of asthma mortality, although this interpretation is limited by the low statistical power of available studies.
Weatherall
M
M
University of Otago Wellington, Wellington, New Zealand.
Wijesinghe
M
M
Perrin
K
K
Harwood
M
M
Beasley
R
R
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000401:mortality; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004812:Epidemiologic Methods; D000068298:Fluticasone; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D001993:Bronchodilator Agents; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol