Tiotropium reduces risk of exacerbations irrespective of previous use of inhaled anticholinergics in placebo-controlled clinical trials

BACKGROUND: Data have highlighted the potential bias introduced by withdrawal of inhaled corticosteroids at randomization in chronic obstructive pulmonary disease trials examining inhaled corticosteroids. Analyses were conducted to determine whether this was true of inhaled anticholinergic withdrawal in tiotropium trials. METHODS: A pooled analysis of randomized, double-blind, placebo-controlled, parallel-group tiotropium trials of at least six months’ duration was performed. Trials had similar inclusion and exclusion criteria. Exacerbation definition was standardized. Patients were divided into two groups, ie, D (anticholinergics discontinued at randomization, previously prescribed) and ND (anticholinergics not discontinued, not previously prescribed). RESULTS: Demographics were balanced between the D (n = 5846) and ND (n = 6317) groups, except for higher cumulative smoking (56 pack-years versus 48 pack-years), lower forced expiratory volume in one second (FEV(1))/forced vital capacity (43% versus 48%), and lower baseline FEV(1) (35.8% predicted versus 42.4% predicted) in the D group. In both groups, tiotropium reduced the risk for an exacerbation (hazard ratio [HR] = 0.83, P < 0.0001 [D] versus 0.79, P < 0.0001 [ND]) and a hospitalized exacerbation (HR = 0.85, P = 0.0467 versus 0.79, P = 0.0094). Tiotropium reduced the number of exacerbations per patient-year (rate ratio [RR] = 0.82, P < 0.0001 [D] versus RR = 0.80, P < 0.0001 [ND]) and associated hospitalizations per patient-year (RR = 0.88, P = 0.015 [D] versus RR = 0.74, P < 0.0001 [ND]). CONCLUSION: Tiotropium reduced exacerbations in patients who did and did not have anticholinergics discontinued upon randomization in clinical trials.