Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

Kyuho Kim, Mercer University College of Pharmacy


A review of two trials stated that the safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. Long-acting beta-agonists are considered to be associated with a potential risk of serious asthma-related events. [1]


A meta-analysis of three studies concluded that there were no asthma-related deaths or imbalances in the rates of asthma-related hospitalization when salmeterol was dispensed in a fixed-dose combination with fluticasone propionate. [2]


Further studies are recommended in order to determine whether the addition of LABAs to inhaled corticosteroids increases the risk of serious asthma outcomes. At this time, it is suggested that there are insufficient data to conclude whether using LABAs with an inhaled corticosteroid reduces or eliminates the risk of asthma-related death and hospitalizations. [3]



Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

Design Prospective, multicenter, randomized, double-blind trial; N= 11,679
Objective To evaluate the risk of administering the LABA (long-acting beta-agonists) salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate
Study Groups Fluticasone- salmeterol (n= 5,834); Fluticasone (n= 5,845)
Methods Patients were randomly assigned in a 1:1 ratio within stratification groups to receive a combination of fluticasone propionate and salmeterol (at a dose of 100 μg of fluticasone and 50 μg of salmeterol, 250 μg and 50 μg, respectively, or 500 μg and 50 μg, respectively) or fluticasone propionate alone (at a dose of 100 μg, 250 μg, or 500 μg), administered twice daily in a masked DISKUS dry-powder inhaler.
Duration November 2011 through June 2015
Primary Outcome Measure First serious asthma-related event, a composite end point that included death, endotracheal intubation, and hospitalization
Baseline Characteristics Characteristic Fluticasone- salmeterol (n= 5,834) Fluticasone alone (n= 5,845)
Female- no. (%) 3,851 (66) 3,898 (67)
Age- mean 43.4 ± 17.45 43.4 ± 17.28
Results Fluticasone- salmeterol (n= 5,834) Fluticasone alone (n= 5,845)
Composite safety end point- no. (%) 34 (0.5%) 33 (0.5%)
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: Respiratory disease (Fluticasone-salmeterol group (2%); fluticasone-only group (2%))
Percentage that Discontinued due to Adverse Events: Fluticasone-salmeterol group (3%); fluticasone-only group (3%)
Study Author Conclusions Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone.


This trial found that the risk of serious asthma-related events was no greater when salmeterol was delivered in a combination with fluticasone than when fluticasone was administered alone. Enrolled patients had moderate-to-severe asthma and patients with histories of life-threatening asthma or exacerbations within the previous 30 days were excluded from the study, which suggests that, the results may not be applicable to all patients with asthma.



1.    Cates CJ, Jaeschke R. Regular treatment with salmeterol and inhaled steroids for chronic asthma: serious adverse events. Cochrane Database Syst Rev2013
2.    Long-acting beta-agonists and adverse asthma events meta-analysis: statistical briefingpackage. Silver Spring, MD: Food and Drug Administration, November 12,2008 
  1. Weatherall M, Wijesinghe M, Perrin K,Harwood M, Beasley R. Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy. Thorax2010;65:39-43

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