Drug Safety

, Volume 29, Issue 8, pp 647–656 | Cite as

Long-Acting β2-Agonists in Asthma

Not so SMART?
  • Graeme P. Currie
  • Daniel K.C. Lee
  • Brian J. Lipworth
Current Opinion


Asthma is a worldwide chronic disorder that is characterised by airway inflammation and hyper-responsiveness, which results in intermittent airflow obstruction and subsequent perception of symptoms and exacerbations. Inhaled corticosteroids are a fundamental component in the prevention of the short- and long-term complications associated with inadequately controlled asthma. However, many individuals experience persistent symptoms and exacerbations despite receiving low-to-medium doses of an inhaled corticosteroid (400–800 μg/day of beclometasone or equivalent). In these symptomatic asthmatic patients, guidelines advocate the initiation of a long-acting β2-adrenoceptor agonist (LABA) as additional second-line controller therapy.

The recent SMART (Salmeterol Multi-centre Asthma Research Trial) study was designed to compare the effects of add-on salmeterol 42 μg (ex-actuator) twice daily with placebo over 28 weeks in a randomised, double-blind, parallel-group fashion, with the intention to enrol 60 000 asthmatic patients. However, the study was halted prematurely because preliminary data revealed an increased mortality associated with regular use of salmeterol. Moreover, concerning rates of respiratory-related deaths, asthma-related deaths and life-threatening events were observed among African Americans, who constituted up to 18% of the study population. This in turn prompted the US FDA to announce important safety information regarding inhalers containing LABAs and advise that new labelling be produced outlining the “ small but significant risk in asthma-related deaths” associated with their regular use. This evidence-based review discusses the data from SMART and highlights potentially important drawbacks with regular use of LABAs in persistent asthma.


Budesonide Fluticasone Propionate Salmeterol Formoterol Persistent Asthma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Graeme P. Currie has received funding from GlaxoSmithKline (who make salmeterol), AstraZeneca (who make formoterol) and Merck & Co. (who make montelukast) for attending postgraduate educational international meetings and honoraria for giving talks. Brian J. Lipworth has received funding for consulting activity from AstraZeneca and grant support from GlaxoSmithKline for a local postgraduate educational activity. Brian J. Lipworth has also received financial support from Merck & Co. for clinical trials and giving postgraduate educational talks. Daniel K.C. Lee has no conflicts of interest that are directly relevant to the content of this review. No sources of funding were used in the preparation of this article.


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Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Graeme P. Currie
    • 1
  • Daniel K.C. Lee
    • 2
  • Brian J. Lipworth
    • 3
  1. 1.Department of Respiratory Medicine, graeme.currie@nhs.netAberdeen Royal InfirmaryForesterhill, AberdeenUK
  2. 2.Department of Respiratory MedicinePapworth HospitalPapworth EverardUK
  3. 3.Division of Medicine & Therapeutics, Asthma & Allergy Research GroupNinewells Hospital & Perth Royal InfirmaryDundeeUK

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