Influence of polytherapy on moderate-to-severe exacerbation rate in patients with severe COPD: focus on β-blockers and SGLT2 inhibitors

<bold>Background:</bold> Given the potential interactions between polypharmacy and inhaled bronchodilator therapy, managing polytherapy in the highly complex COPD patient is not always easy. Several observational studies suggest that β-blockers benefit patients with COPD and coexisting cardiovascular disease, and there is limited data on sGLT2 inhibitors. The aim of this study was to determine whether polytherapy, B-blocker use or SGLT2-I use may influence clinical severity and the incidence of acute moderate-to-severe exacerbations. <bold>Materials and methods:</bold> Prospective observational study including 120 patients with a confirmed diagnosis of COPD according to the GOLD 2023 report and at high risk of exacerbations. Each participant was followed up for 12 months. The primary outcome was a composite of moderate or severe exacerbations within 12 months after the last acute severe exacerbation. <bold>Results:</bold> The total number of daily drugs showed a significant positive correlation with dyspnoea severity as assessed by the mMRC scale (ρ=0.452, p < 0.001) and a significant negative correlation with spirometric indices. The multivariate logistic model showed a higher rate of moderate to severe exacerbations in participants treated with β-blockers (odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.41-10.27, p < 0.01), on long-term oxygen (OR = 2.78, 95% CI=1.03-7.47, p=0.04) and a lower risk in those treated with SGLT2-i (OR: 0.66; CI=0.26-0.78, p=0.015). <bold>Conclusions:</bold> Among patients with COPD, the risk of moderate-to-severe exacerbations was higher in those with an higher number of daily drugs or taking β-blockers and lower in those treated with SGLT2-i.