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

Abstract

Objective

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

Design

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.

Setting

UK healthcare system general practitioner electronic medical record database.

Participants

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.

Primary and secondary outcome measures

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

Results

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.

Conclusion

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.

Article summary

Article focus

• This study investigated whether there are possible increased risks of stroke and other adverse events, including angina and myocardial infarction, with tiotropium use in chronic obstructive pulmonary disease.

• The authors compared new users of long-acting anticholinergic therapy (tiotropium HandiHaler®) with new users of LABA monotherapy.

Key messages

• Compared with LABA, tiotropium HandiHaler was associated with increased risks of angina, myocardial infarction and stroke and lower risk of total mortality.

• The results of this study are similar to results from a recent clinical trial comparing tiotropium with salmeterol and support the hypothesis that tiotropium HandiHaler can be associated with an increased risk of ischaemic cardiovascular events.

Strengths and limitations of this study

• Strengths of this study are the new user design and use of propensity scores to control for available risk factors, including demographic factors, history of respirator, cardiovascular and other illness and respiratory, cardiovascular and other medications.

• Limitations of this study are that routine lung function measures were unavailable, and composite end points of all-cause mortality and all strokes may attenuate associations for cardiovascular mortality and ischaemic stroke.