Eric Bateman, MD; Harold Nelson, MD; Jean Bousquet, MD; Kenneth Kral, MS; Laura Sutton, PharmD; Hector Ortega, MD, ScD; Steven Yancey, MS
Recent analyses have suggested an increased risk for serious asthma-related adverse events in patients receiving long-acting Î²-agonists.
To examine whether the incidences of severe asthma-related events (hospitalizations, intubations, deaths, and severe exacerbations) differ in persons receiving salmeterol plus inhaled corticosteroids compared with inhaled corticosteroids alone.
The GlaxoSmithKline (Research Triangle Park, North Carolina) database, MEDLINE, EMBASE, CINAHL, and the Cochrane Database of Systemic Reviews (1982 to September 2007) were searched without language restriction.
Randomized, controlled trials reported in any language that compared inhaled corticosteroids plus salmeterol (administered as fluticasone propionate/salmeterol by means of a single device or concomitant administration of inhaled corticosteroids and salmeterol) versus inhaled corticosteroids alone in participants with asthma.
Three physicians independently reviewed and adjudicated blinded case narratives on serious adverse events that were reported in the GlaxoSmithKline trials.
Data from 66 GlaxoSmithKline trials involving a total of 20Â 966 participants with persistent asthma were summarized quantitatively. The summary risk difference for asthma-related hospitalizations from these trials was 0.0002 (95% CI, âˆ’0.0019 to 0.00231; P = 0.84) for participants receiving inhaled corticosteroids plus salmeterol (n = 35 events) versus those receiving inhaled corticosteroids alone (n = 34 events). One asthma-related intubation and 1 asthma-related death occurred among participants receiving inhaled corticosteroids with salmeterol; no such events occurred among participants receiving inhaled corticosteroids alone. A subset of 24 trials showed a decreased risk for severe asthma-related exacerbations for inhaled corticosteroids plus salmeterol versus inhaled corticosteroids alone (risk difference, âˆ’0.025 [CI, âˆ’0.036 to âˆ’0.014]; P <0.001).
The included trials involved selected patients who received careful follow-up. Only 26 trials were longer than 12 weeks. Few deaths and intubations limited the ability to measure risk for these outcomes.
Salmeterol combined with inhaled corticosteroids decreases the risk for severe exacerbations, does not seem to alter the risk for asthma-related hospitalizations, and may not alter the risk for asthma-related deaths or intubations compared with inhaled corticosteroids alone.
Guidelines recommend adding long-acting β-agonists to regimens of patients with asthma that is not controlled on inhaled corticosteroids alone. Is this safe?
This meta-analysis summarizes 66 GlaxoSmithKline trials involving 20 966 patients with persistent asthma. Trials compared twice-daily salmeterol, 50 μg, plus inhaled corticosteroids with inhaled corticosteroids alone. Combination therapy did not appear to alter risk for asthma-related hospitalizations but did decrease risk for severe exacerbations requiring systemic corticosteroids. The only cases of asthma-related death and intubation occurred in patients receiving combination therapy.
Most trials were short and originally designed to assess lung function rather than clinical outcomes.
GSK = GlaxoSmithKline.
*Studies could contribute to more than 1 subanalysis.
Appendix Table 1.
*Number of events/total population.
Appendix Table 2.
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Bateman E, Nelson H, Bousquet J, Kral K, Sutton L, Ortega H, et al. Meta-analysis: Effects of Adding Salmeterol to Inhaled Corticosteroids on Serious Asthma-Related Events. Ann Intern Med. 2008;149:33-42. doi: 10.7326/0003-4819-149-1-200807010-00229
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Published: Ann Intern Med. 2008;149(1):33-42.
Asthma, Pulmonary/Critical Care.
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