Risk Factors for All-Cause Mortality in Patients with COPD: Results from the ETHOS Trial

Background: Triple therapy with budesonide/glycopyrronium/formoterol (BGF) 320/14.4/10µg reduced all-cause mortality (ACM) risk vs dual therapies, with a significant reduction (HR 0.51; unadjusted p=0.0035) vs glycopyrronium/formoterol (GFF) in the 52-week ETHOS trial of COPD (NCT02465567). Aim: To assess the impact of baseline risk factors on ACM in ETHOS. Methods: Patients with moderate-to-very severe COPD and ≥1 moderate/severe exacerbation in the prior year were randomized to BGF 320 or 160/14.4/10µg, GFF 14.4/10µg, or budesonide/formoterol 320/10µg. All treatments were administered twice-daily via a metered dose Aerosphere inhaler. ACM incidence was tabulated into subgroups, and for continuous variables, relationships were investigated using generalized additive modelling. Results: For the ITT population overall (n=8509), ACM generally increased with older age, lower FEV1 % predicted, higher CAT score, and a greater number of CV risk factors, and was higher in males vs females (Table). There was no clear impact of smoking status (current vs former) on ACM. In the GFF group alone, ACM increased with eosinophil count. Across the majority of subgroups, ACM was lower on BGF 320 vs dual therapies. Conclusion: Demographic and disease characteristics influence absolute risk of ACM in COPD. Triple therapy with BGF 320 reduced ACM vs dual therapies across subgroups, demonstrating benefits for a broad range of patients with COPD.