Is overreliance on short-acting β₂-agonists associated with health risks in the older asthma population?

Abstract

Recent Global Initiative for Asthma (GINA) recommendations reduce the role of short-acting beta-agonist (SABA) premised on the associated exacerbation risk. The widely accepted SABA risk profile is based on limited data described 30 years ago. This GINA paradigm shift demands an examination of SABA risks in a modern therapeutic era. Recent studies confirm that SABA overuse is common and associated with adverse outcomes. This study aimed to determine associations between SABA use, all-cause mortality, and asthma exacerbations in an older North American asthma population.In this population-based cohort study, individuals with prevalent asthma (2006–2015) aged ≥65 years, eligible for provincial drug coverage, were included. Annual SABA canisters filled (0, 1–2, 3–5, ≥6) was the primary exposure. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox-Proportional Hazard regression, adjusted for confounders.There were 59 533 asthma individuals; 14% overused SABA (≥3 canisters annually). Compared to those who used <3 canisters, the adjusted HRs of death for those who used 3–5 and ≥6 canisters were 1.11 (95%CI: 1.02–1.22, p=0.0157) and 1.56 (95%CI: 1.41–1.71, p<0.0001), respectively. Severe asthma exacerbation rates for ≥3 and <3 canisters/year were 7.5% and 2.1%, respectively. The adjusted HRs of severe asthma exacerbations were 1.59 (95%CI: 1.40–1.82, p<0.0001) and 2.26 (95%CI: 1.96–2.60, p<0.0001) in those who used 3–5 and ≥6 SABA canisters per year, respectively.In Canada, 1/7 individuals with asthma overused SABA associated with an increased risk of severe asthma exacerbations and death. The adverse impacts of SABA overuse continue 30 years after early publications.

SABA use as an indicator for asthma exacerbation risk: an observational cohort study (SABINA Canada)

“…SABA overuse was associated with an increased rate of severe exacerbations and this association remained when stratified by ICS use (six or more canisters of ICS per year). The results of the present study are consistent with prior Canadian studies characterising SABA use nearly two decades ago [ 7 ] and those describing an association with higher risk of mortality and other poor health outcomes [ 21 , 24 , 30 ]. F itz G erald et al .…”

“…They found that inappropriate SABA use was associated with a 45% increased risk of hospital admissions and a 25% increased risk of emergency department visits in the 3-month period following that inappropriate use [ 7 ]. In addition, a recent Canadian study including patients ≥65 years of age with prevalent asthma found 14% of patients to have overused SABA (three or more canisters per year) and an associated increased risk of severe asthma exacerbations, ranging from 59–126% among those using three to five canisters and six or more canisters per year [ 24 ]. Thus, while definitions of SABA overuse vary in specificity [ 38 ], the association between overuse of SABA and poor health outcomes is consistent with the results found in our study.…”

“…As a result, they may undervalue adherence to maintenance therapy and simply increase SABA use when symptoms arise. While there have been some targeted studies of the use of SABA in Canada [ 24 ], little has been done to quantify the scale of overuse and the impact on patient outcomes.…”

“…While there have been some targeted studies of the use of SABA in Canada 24 , little has been done to quantify the scale of overuse and the impact on patient outcomes.…”

Expert Consensus on SABA Use for Asthma Clinical Decision-Making: A Delphi Approach

“…It is by now well established that SABA overuse is widespread and is linked to poor asthma outcomes [ 10 ••, 12 , 32 •]. The SABINA study investigators reported that the greater the number of SABA canisters prescribed per year, the greater the odds of patients having uncontrolled asthma [ 10 ••].…”