The impact of tiotropium on mortality when added to inhaled corticosteroids and long-acting beta agonist therapy in COPD

Background and objectives: Tiotropium (TIO) has been shown to improve lung function, quality of life and reduce mortality and exacerbations in COPD.However it remains unclear whether such benefits are seen when TIO is used in conjunction with inhaled corticosteroid (ICS) plus long acting beta-2 agonists (LABA). Methods: Retrospective Cohort study using linked NHS databases on hospital admissions, COPD outcomes, prescribing and mortality. Cox proportional hazard regression analysis was used to assess the addition of TIO to ICS+LABA on mortality and exacerbations. History of respiratory and cardiovascular disease, Sex, Age and smoking history were used as covariates. We observed lung function in each group over the study period. Results: 3004 COPD patients were included in the study. 2082 patients were prescribed ICS+LABA+Tio and 922 were prescribed ICS+LABA. Mean follow- up 4.65 years. Mean age 68.5 years. 1035 patients died during the study. The adjusted hazard ratio for all-cause mortality for ICS+LABA+TIO vs ICS+LABA was 0.67 (95% CI, 0.58-0.76) p<0.001. Adjusted hazard ratios for respiratory hospital admissions and oral corticosteroid use were 0.86 (95% CI 0.74-0.99) p=0.043 and 0.72 (95% CI 0.65-0.81) p<0.001. In the ICS+LABA group (mean FEV1% pred 66.8%), mean first and last FEV1 and FVC (L) were 1.56 vs 1.57 and 2.64 vs 2.72. In the ICS+LABA+Tio group, (mean FEV1% pred 51.6%), mean first and last FEV1 and FVC (L) were 1.24 vs 1.20 and 2.47 vs 2.50. Conclusions: We have shown that the addition of TIO to ICS+LABA reduces all-cause mortality in our COPD population. Reductions in COPD exacerbations and oral steroid use reaffirm findings of previous studies.