long acting beta agonists (LABA s) and morbidity and mortality

Last reviewed 07/2022

• there is evidence that treating patients with long acting beta agonists (LABAs) results in a small but significant increase in death and other major adverse outcomes
  • randomized, placebo-controlled trials that lasted at least 3 months and evaluated long-acting beta-agonist use in patients with asthma. All trials allowed the use of as-needed short-acting beta-agonis
  • pooled results from 19 trials with 33 826 participants found that long-acting beta-agonists increased exacerbations requiring hospitalization (OR, 2.6 [95% CI, 1.6 to 4.3]) and life-threatening exacerbations (OR, 1.8 [CI, 1.1 to 2.9]) compared with placebo. Hospitalizations were statistically significantly increased with salmeterol (OR, 1.7 [CI, 1.1 to 2.7]) and formoterol (OR, 3.2 [CI, 1.7 to 6.0]) and in children (OR, 3.9 [CI, 1.7 to 8.8]) and adults (OR, 2.0 [CI, 1.1 to 3.9]). The absolute increase in hospitalization was 0.7% (CI, 0.1% to 1.3%) over 6 months. The risk for asthma-related deaths was increased (OR, 3.5 [CI, 1.3 to 9.3]), with a pooled risk difference of 0.07% (CI, 0.01% to 0.1%
  • the study authors concluded that long-acting beta-agonists have been shown to increase severe and life-threatening asthma exacerbations, as well as asthma-related deaths
  • a commentary on this study concluded that "LABA monotherapy should not be used in patients with asthma....underscores the need for LABAs to be used only as a component of combined inhaled corticosteroids and LABA therapy. (2)"
• more recent data from a further meta-analysis, an observational study and a large three-year randomised controlled trial (RCT) are reassuring about the safety of LABAs (3)
  • however, in view of the concerns raised about the safety of these drugs in asthma, the Medicines and Healthcare products Regulatory Agency (MHRA) continues to monitor the safety of LABAs in both asthma and COPD (3)

Reference:

1. Salpeter SR et al. Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med. 2006 Jun 20;144(12):904-12
2. Smith BJ, Roy A. Evidence Based Medicine 2007;12:10.
3. . MeReC Bulletin 2009; 19 (4)