High use of short-acting beta-2-agonists in COPD is associated with an increased risk of exacerbations and mortality

16 May 2023

Introduction: Short-acting beta-2-agonist (SABA) overuse has been associated with an increased risk of exacerbations in asthma. However, less is known about SABA use in chronic obstructive pulmonary disease (COPD). Our aim was to describe SABA use and associations between high SABA use and the risk of future exacerbations and mortality in COPD.

Method: This observational study identified COPD patients in primary care medical records in Sweden. Data were linked to the National Patient Registry, the Prescribed Drug Registry, and the Cause of Death Registry. The index date was set 12 months after the date of COPD diagnosis. Data about SABA use were collected over 12 months pre-index, and about exacerbations and mortality over 12 months post-index.

Results: Of the 19,794 COPD patients included (mean age 69.1 years, 53.3% females), 15.5% and 7.0% had collected ≥3 or ≥6 SABA canisters during baseline, respectively; and 43.6% an inhaled corticosteroid (ICS). A SABA use ≥6 canisters was independently associated with a higher risk of both moderate and severe exacerbations (hazard ratio, HR, 1.28 [95% CI 1.17‒1.40] and 1.76 [1.50‒2.06], respectively). 3.4% died between the index and the 12-month post-index date. An independent association was found between high SABA use and overall mortality (HR 1.60 [1.07‒2.39]). This association, however, was not found in patients concomitantly collecting ICS as maintenance treatment (76.2%).

Discussion: Not only in asthma, but also in COPD, a high SABA use is relatively common and associated with an increased risk of future exacerbations and mortality, especially in patients without ICS. We suggest that clinicians ask patients about SABA use as a measure of disease control, to guide potential treatment escalation. Further discussions should include the role of SABA overuse as an indicator of severe COPD and whether SABA overuse is unbeneficial per se due to development of tolerance to beta-2-agonists.

Resource information

Respiratory conditions
  • COPD
Respiratory topics
  • Treatment - drug
Type of resource
Munich 2023
Christer Janson 1, Fredrik Wiklund 2, Gunilla Telg 3, Georgios Stratelis 3, Hanna Sandelowsky 4,5,6 1 Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, , Uppsala, Sweden, 2 Statisticon AB, Uppsala, Sweden, 3 AstraZeneca Nordic, Stockholm, Sweden, 4 Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm , Sweden, 5 Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden, 6 Academic Primary Health Care Centre, Region Stockholm, Stockholm, Sweden