Article Text

Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy
  1. M Weatherall1,2,
  2. M Wijesinghe2,3,
  3. K Perrin2,3,
  4. M Harwood3,
  5. R Beasley2,3,4
  1. 1
    University of Otago Wellington, Wellington, New Zealand
  2. 2
    Capital & Coast District Health Board, Wellington, New Zealand
  3. 3
    Medical Research Institute of New Zealand, Wellington, New Zealand
  4. 4
    University of Southampton, Southampton, UK
  1. Correspondence to Professor R Beasley, Medical Research Institute of New Zealand, P O Box 10055, Wellington 6143, New Zealand; richard.beasley{at}


Background: There is concern that long-acting β 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.

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  • Funding The study was funded by a grant of NZ$24 000 from MedSafe, New Zealand Ministry of Health. MW is a Wellington Hospitals and Health Foundation Research Fellow and KP is a Health Research Council of New Zealand Training Fellow. The study sponsors had no role in study design, data collection, analysis, data interpretation, writing of the report or in the decision to submit the paper for publication.

  • Competing interests The Medical Research Institute of New Zealand has received research grants from AstraZeneca, GlaxoSmithKline and Novartis. RB has received fees for consulting and speaking and reimbursement for attending symposia from AstraZeneca, GlaxoSmithKline and Novartis. All other authors have no conflict of interest.

  • Provenance and Peer review Not commissioned; externally peer reviewed.