Association between overuse of short-acting β2-agonists and the risk of major adverse cardiovascular events among patients with asthma

BACKGROUND: Short-acting β2-agonist (SABA) overuse is associated with increased asthma exacerbations and mortality, yet its impact on cardiovascular disease remains unclear. We investigate the association between SABA overuse and the risk of major adverse cardiovascular events (MACE) in patients with asthma. METHODS: Between 2011 and 2019, patients with asthma were identified from the Taiwan asthma pay-for-performance database. SABA overuse was defined as using ≥3 canisters annually, compared with acceptable use (0-2 canisters/year). Inverse probability of treatment weighting (IPTW) was applied to balance baseline covariates. The primary outcome was 1-year MACE. Secondary outcomes included MACE component (non-fatal myocardial infarction, haemorrhagic stroke, ischaemic stroke) and mortality. RESULTS: Among 231 970 patients, 28 500 had SABA overuse and 203 470 had acceptable use. In the IPTW-weighted cohort, 1-year MACE incidence was higher in the overuse group (2.82 vs 0.99 per 100 person-years; adjusted HR (aHR) 1.25, 95% CI 1.12 to 1.39). SABA overuse significantly increased the risk of non-fatal MI (aHR: 1.28, 95% CI 1.09 to 1.50), ischaemic stroke (aHR: 1.26, 95% CI 1.08 to 1.46) and mortality (aHR: 1.40, 95% CI 1.24 to 1.58). Haemorrhagic stroke risk was not significantly increased. A non-linear dose-response was observed, with MACE risk peaking at 6-8 canisters annually. CONCLUSION: SABA overuse (≥3 canisters/year) is associated with increased risks of MACE and mortality in patients with asthma. These findings emphasise the importance of monitoring SABA use and assessing cardiovascular risk in asthma management.