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Safety of Long-Acting Beta-Agonists: Are New Data Really Required?
Chest. 2009 Jun 8;
Authors: Sears MR
Despite 20 years of debate, several Food and Drug Administration (FDA) hearings, black-box warnings, and many descriptive papers and meta-analyses, controversy regarding the safety of long-acting beta-agonist (LABA) treatment in asthma continues. This has resulted in a recent call for another large and definitive safety study. This commentary focuses firstly on data provided in the metaanalysis recently undertaken by the FDA of safety outcomes among 60,954 individuals in 110 LABA trials, and secondly on the sample size which would be required for a new definitive study of LABA safety in the presence of mandatory inhaled corticosteroid (ICS). A critical stratified analysis in the FDA report involving 15,192 individuals indicates that LABA used with mandatory ICS was not associated with an increased risk of asthma-related mortality, intubations or exacerbations (Risk Difference [RD] 0.25 per 1000 individuals, 95% Confidence Interval (CI) -1.69 to 2.18). Using the same stratified data to calculate the sample size required to prove or disprove an association between use of LABA with mandatory ICS and adverse outcomes, assuming the RD is exactly 0.25 and ignoring the 95% CI which includes 0.0 or even a negative risk, such a study is both logistically and scientifically impossible. A new study is not practicable, nor is one needed in the light of current analyses of existing data. It is time to learn from the past, to rigorously avoid LABA monotherapy in asthma, and to use LABA (when indicated) always in mandatory combination with appropriate doses of ICS.
PMID: 19505986 [PubMed - as supplied by publisher]