Safety with use of long-acting β₂-selective agonists for asthma

Since their introduction more than 50 years ago, use of β-agonists for inhalation has been associated with increased mortality. Since the turn of the century, particular concern has been voiced regarding long-acting β2-selective agonists. Our purpose was to investigate the evidence from recently published randomised trials of possible increased risks of death and serious adverse events related to exposure to these drugs.

A PubMed search identified ten clinical trials which fulfilled predefined inclusion criteria.

The ten trials encompassed 66 664 patients. A total of 16 asthma-related deaths after exposure to long-acting β2-selective agonists were recorded among 33 043 actively treated patients, whereas four such deaths were recorded among the 33 621 patients in the control groups. A single, large, pragmatic trial accounts for a majority of these fatalities.

Exposure to long-acting β2-selective agonists is associated with a small increase in mortality. Whether concomitant use of inhalation steroids fully reverses this effect is not clear.