Inhaled tiotropium bromide and risk of stroke

Abstract

Aims: A recent communication from the United States Food and Drug Administration highlighted a possible increased risk of stroke associated with use of the relatively new inhaled anticholinergic drug, tiotropium bromide. Using the United Kingdom General Practice Research Database, we set out to assess the risk of stroke in individuals exposed to inhaled tiotropium bromide and two other inhaled treatments for airways disease.

Methods: We used the self-controlled case-series that reduces confounding and minimizes the potential for biases in the quantification of risk estimates.

Results: Of 1043 people with a diagnosis of incident stroke who had had at least one prescription for tiotropium bromide, 980 satisfied inclusion criteria. The age-adjusted incidence rate ratio for all-cause stoke in individuals exposed to tiotropium bromide (n = 980), ipratropium bromide (n = 4181) and fluticasone propionate/salmeterol xinafoate (n = 1000) was 1.1 [95% confidence interval (CI) 0.9, 1.3], 0.8 (95% CI 0.7, 0.9) and 1.0 (95% CI 0.9, 1.2), respectively.

Conclusions: We found no evidence of an increased risk of all-cause stroke for individuals exposed to commonly prescribed inhaled treatments for chronic obstructive pulmonary disease.

Figure 1

Pictorial representation of the self-controlled case-series method where age-adjusted incidence rate ratios of the outcome of interest are derived comparing defined intervals during the exposure period (drug administration and wash-out period) relative to all other observed time periods (baseline period) for each person. Baseline Period (); Drug Administration Period (); Wash-out Period ()

Figure 2

Meta-analysis of randomized trials of inhaled tiotropium bromide vs. control for the adverse outcome of stroke