A new user cohort study comparing the safety of long-acting inhaled bronchodilators in COPD

To investigate a possible increased risk observed in tiotropium clinical trials of stroke and other adverse events.

New users of long-acting anticholinergic therapy (tiotropium HandiHaler®) were compared with new users of long-acting β-agonist (LABA) monotherapy, and propensity scores were used to control confounding.

UK healthcare system general practitioner electronic medical record database.

10 840 patients newly prescribed tiotropium (n=4767) or LABA (n=6073), at least 40 years old, and not having asthma as their only respiratory illness.

Incidence rates of total stroke, myocardial infarction, angina and other adverse events.

Tiotropium was associated with increased rates of stroke (HR=1.49, 95% CI 0.91 to 2.45), angina (HR=1.38, 95% CI 0.88 to 2.16) and myocardial infarction (HR=1.26, 95% CI 0.72 to 2.21). Groups had similar rates of chronic obstructive pulmonary disease exacerbation (HR=0.95, 95% CI 0.80 to 1.12) and pneumonia (HR=0.96, 95% CI 0.58 to 1.58). Tiotropium was associated with a lower rate of total mortality (HR=0.70, 95% CI 0.56 to 0.89) and asthma exacerbations (HR=0.46, 95% CI 0.36 to 0.57) than users of LABA.

Small increased risks of serious ischaemic cardiovascular events have been reported with inhaled anticholinergic medication from randomised and nonrandomized studies of ipratropium, tiotropium HandiHaler® and tiotropium Respimat®. Additional research is needed to understand the full extent of cardiovascular effects of inhaled anticholinergic medications and the patients who may be most susceptible.