Are long-acting beta agonists (LABAs), with or without inhaled corticosteroids, safe in the treatment of adult asthma?
LABAs appear to be safe when used with inhaled corticosteroids. LABA monotherapy is associated with an increase in asthma-related mortality and nonfatal serious adverse events, but not in all-cause mortality.1 (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)
Asthma affects 8.2% of the U.S. population, and disproportionately affects those who are poor and black. Despite effective therapies, 3,404 U.S. deaths were attributed to asthma in 2010.1 Two types of inhaled pharmacologic agents are used for asthma control: inhaled corticosteroids and LABAs. Concerns about the safety of LABAs have risen with reports of increased hospital admissions and deaths.
This Cochrane review focused on LABA safety in adults with asthma. The authors included six previous reviews and five new randomized trials totaling 70,444 persons 12 years and older. There was no significant increase in all-cause mortality with LABA monotherapy compared with placebo (odds ratio [OR] = 1.37; 95% confidence interval [CI], 0.88 to 2.13; n = 33,952). However, asthma-related deaths were higher in those taking LABA monotherapy (OR = 3.54; 95% CI, 1.36 to 9.19; n = 33,313), and LABA monotherapy was associated with a small increase in nonfatal serious adverse events (i.e., events that are life-threatening, require hospitalization, or result in significant disability; OR = 1.14; 95% CI, 1.02 to 1.29; n = 35,954).
All-cause mortality did not increase among patients using LABA/inhaled corticosteroid combination therapy compared with those using inhaled corticosteroid monotherapy (OR = 1.42; 95% CI, 0.60 to 3.38; n = 24,718). Only one asthma-related death occurred among these patients. There was no significant increase in nonfatal serious adverse events in the LABA/inhaled corticosteroid group vs. the inhaled corticosteroid monotherapy group (OR = 1.07; 95% CI, 0.90 to 1.27; n = 24,718). Because of differing study methodologies, the authors were unable to compare deaths among patients on LABA monotherapy and those on LABA/inhaled corticosteroid combination therapy.
Multiple organizations have issued guidelines on the use of LABAs. The Department of Veterans Affairs/Department of Defense guidelines state that LABAs are contraindicated as monotherapy for maintenance treatment of asthma, but they do allow adding LABAs to an inhaled corticosteroid for persistent asthma.2 Similarly, the Institute for Clinical Systems Improvement states that after a patient starts a medium-dose inhaled corticosteroid, a LABA may be added to enhance control. It also recommends against the use of LABA monotherapy.3 The British Thoracic Society states that LABAs should be used only in patients already taking an inhaled corticosteroid.4 A prudent approach would be to use an inhaled corticosteroid as first-line treatment for patients with persistent asthma; LABAs are best reserved as adjunct treatment for those already taking an inhaled corticosteroid.