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, 8, 53-64

The Safety of Long-Acting β2-agonists in the Treatment of Stable Chronic Obstructive Pulmonary Disease


The Safety of Long-Acting β2-agonists in the Treatment of Stable Chronic Obstructive Pulmonary Disease

Marc L Decramer et al. Int J Chron Obstruct Pulmon Dis.


Background: Inhaled long-acting bronchodilators are the mainstay of pharmacotherapy for chronic obstructive pulmonary disease (COPD). Both the twice-daily long-acting β(2)-adrenoceptor agonists (LABAs) salmeterol and formoterol and the once-daily LABA indacaterol are indicated for use in COPD. This review examines current evidence for the safety of LABAs in COPD, focusing on their effect on exacerbations and deaths.

Methods: We searched PubMed for placebo-controlled studies evaluating long-term (≥24 weeks) use of formoterol, salmeterol, or indacaterol in patients with stable COPD, published between January 1990 and September 2012. We summarized data relating to exacerbations and adverse events, particularly events related to COPD.

Results: From 20 studies examined (8774 LABA-treated patients), there was no evidence of an association between LABA treatment and increased exacerbations, COPD-related adverse events, or deaths. Where analyzed as an efficacy outcome, LABA treatment was generally associated with significant or numerical reductions in COPD exacerbations compared with placebo. Incidences of COPD-related adverse events were similar for active and placebo treatments. The incidence of adverse events typically associated with the β(2)-agonist drug class such as skeletal muscle tremors and palpitations was low (often <1% of patients), and there were no reports of increased incidence of cardiac arrhythmias. The systemic effects of β(2)-adrenoceptor stimulation, such as high glucose and potassium levels, were considered minor.

Conclusion: Current evidence from clinical studies of the safety and tolerability profile of LABAs supports their long-term use in COPD.

Keywords: COPD; LABA; bronchodilator; formoterol; indacaterol; salmeterol.

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    1. Centers for Disease Control and Prevention Deaths: preliminary data for 2009 National Vital Statistics Reports 2011594Available from: September 28, 2012
    1. World Health Organization (WHO) Chronic respiratory diseases: chronic obstructive pulmonary disease [web page on the Internet] Geneva: WHO Chronic Diseases and Health Promotion Department; nd. Available from: December 3, 2012
    1. O’Donnell DE. Hyperinfation, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2006;3(2):180–184. - PubMed
    1. O’Donnell DE. Dynamic lung hyperinflation and its clinical implication in COPD. Rev Mal Respir. 2008;25(10):1305–1318. French. - PubMed
    1. Global Initiative for Chronic Obstructive Lung Disease (GOLD) global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary DiseaseRev ed. GOLD; 2011Available from: June 14, 2012

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