Statins lower outpatient and hospitalised exacerbation risk beyond exacerbation history

<bold>Background:</bold> We previously demonstrated that statins may improve lung function trajectories in adults of the general population, even in those without lung function deficits, while other studies suggest that benefits only apply to certain subgroups. <bold>Aim:</bold> To investigate whether statins lower outpatient and hospitalised exacerbation risk in obstructive airway disease drugs users depending on exacerbation history. <bold>Methods:</bold> Patients ≥ 18 years obtaining 2 claims for obstructive airway disease drugs in 1 year between 2017-2022 were identified in Belgian nationwide claims-based data. A multivariable Cox model examined the effect of statins on outpatient and hospitalised exacerbations adjusted for age, sex, smoking, Charlson Comorbidity Index, socioeconomic status, vaccination, short-acting bronchodilators overuse, frailty, and stratified by exacerbation history. <bold>Results:</bold> Among 980,120 patients (aged 60 years, 54% female, 24% ever-smokers), 290,508 (29.6%) used statins, 777,973 (79.4%) had no exacerbations, and 78,515 (8.0%) had ≥ 2 outpatient or 1 hospitalised exacerbation in the previous year. During follow-up, 265,787 (27.1%) had an outpatient treated exacerbation, and 38,231 (3.9%) were hospitalised. Statins significantly reduced outpatient and hospitalised exacerbation risk by 6% (aHR 0.94, 95%CI 0.93-0.95) and 11% (aHR 0.89, 95%CI 0.87-0.91), respectively. Stratified by exacerbation history, statins also reduced outpatient and hospitalised exacerbation risk in those with ≤ 1 outpatient-treated exacerbation. <bold>Conclusion:</bold> Statins lower exacerbation risk in obstructive airway disease drugs users, even in those without frequent exacerbations, supporting their broader role in respiratory disease control.