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Effects of Adding Salmeterol to Inhaled Corticosteroids on Serious Asthma-Related Events


Recent analyses have suggested an increased risk for serious asthma-related adverse events in patients receiving long-acting β-agonists.

Purpose: 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.

Study Selection: 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.

Data Extraction: Three physicians independently reviewed and adjudicated blinded case narratives on serious adverse events that were reported in the GlaxoSmithKline trials.

Data Synthesis: Data from 66 GlaxoSmithKline trials involving a total of 20 966 participants with persistent asthma were summarized quantitatively. The summary risk difference for asthma-related hospitalizations from these trials was 0.0002 (95% CI, –0.0019 to 0.0023; P = 0.84) for participants receiving inhaled corticosteroids with salmeterol (n = 35 events) versus those receiving inhaled corticosteroids alone (n = 34 events). There was 1 asthma-related intubation and 1 asthma-related death 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, –0.025 [CI, –0.036 to –0.014; P < 0.001]).

Limitations: The included trials involved selected patients that received careful follow-up. Only 26 trials were longer than 12 weeks. Few deaths and intubations limited ability to measure risk for these outcomes.

Conclusion: 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.

Source: Annals of Internal Medicine, Volume 149 Issue 1