Safety of long-acting beta-agonists in stable COPD: a systematic review

Chest. 2008 May;133(5):1079-87. doi: 10.1378/chest.07-1167.


Background: Some studies have suggested that use of long-acting beta(2)-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 (> or = 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adrenergic beta-Agonists / therapeutic use*
  • Bronchoconstriction / drug effects
  • Delayed-Action Preparations / therapeutic use
  • Disease Progression
  • Humans
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Secondary Prevention
  • Severity of Illness Index
  • Treatment Outcome


  • Adrenergic beta-Agonists
  • Delayed-Action Preparations