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Safety of Long-Acting β-Agonists in Stable COPD^*

A Systematic Review

^* From the Departamento de Emergencia (Dr. Rodrigo), Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay; Sección Neumonología (Dr. Nannani), Hospital G. Baigorria, Universidad Nacional de Rosario, Santa Fe, Argentina; and Servei de Pneumologia (Institut del Tòrax) [Dr. Rodríguez-Roisin], Hospital Clínic, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS Ciber Enfermedades Respiratorias), Universitat de Barcelona, Barcelona, Spain.

Correspondence to: Gustavo J. Rodrigo, MD, Departamento de Emergencia, Hospital Central de las Fuerzas Armadas, Av. 8 de Octubre 3020, Montevideo 11600, Uruguay; e-mail: gurodrig{at}adinet.com.uy

Abstract

Background: Some studies have suggested that use of long-acting β₂-agonists (LABAs) leads to an increased risk for adverse events in patients with stable COPD. The purpose of this review was to assess the safety, and secondarily the efficacy of LABAs.

Methods: The authors conducted a systematic review with metaanalysis of randomized clinical trials ( 1 month in duration) in the published literature that have compared LABAs with placebo or anticholinergics in stable poorly reversible and reversible COPD.

Results: MEDLINE, EMBASE, CINAHL, and the Cochrane Controlled Trials Register were searched to identify 27 studies. LABAs reduced severe exacerbations compared with placebo (relative risk [RR], 0.78; 95% confidence interval [CI], 0.67 to 0.91). There was no significant difference between LABA and placebo groups in terms of respiratory deaths (RR, 1.09; 95% CI, 0.45 to 2.64). Use of LABAs with inhaled corticosteroids reduced the risk of respiratory death compared with LABAs alone (RR, 0.35; 95% CI, 0.14 to 0.93). Patients receiving LABAs showed significant benefits in airflow limitation measures, health-related quality of life, and use of rescue medication. Finally, tiotropium decreased the incidence of severe COPD exacerbations compared with LABAs (RR, 0.52; 95% CI, 0.31 to 0.87).

Conclusion: This review supports the beneficial effects of the use of LABAs in patients with stable moderate-to-severe COPD, and did not confirm previous data about an increased risk for respiratory deaths. Also, our analysis suggests the superiority of tiotropium over LABAs for the treatment of stable COPD patients.

Key Words: bronchodilators • COPD • formoterol • long-acting β₂-agonists • salmeterol • tiotropium

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