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.
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To cite: Jara M, Wentworth C, Lanes S. A new user cohort study comparing the safety of long-acting inhaled bronchodilators in COPD. BMJ Open 2012;2:e000841. doi:10.1136/bmjopen-2012-000841
Contributors All authors made substantial contributions to conception and design of the study. MJ and CW acquired the data and conducted the analysis. All authors contributed substantially to data interpretation. MJ and SL drafted the manuscript, and all authors reviewed and revised the manuscript for important intellectual content. All authors approved the final version.
Funding Boehringer Ingelheim Pharmaceuticals.
Competing interests Dr MJ is employed by Acorda Therapeutics, Hawthorne, NY. Dr SL and Mr Wentworth are employed by United BioSource Corporation, Lexington, MA. The study was funded by Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT. Two of the authors (MJ and SL) were employees of Boehringer Ingelheim at the time the study was conducted. CW served as a consultant. Boehringer Ingelheim granted the authors permission to publish this study. The authors are solely responsible for the design, analysis, interpretation and conclusions of the study.
Ethics approval This study received ethical approval from the UK Department of Health Multicentre Research Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Data sets for this study are the property of Boehringer Ingelheim and not currently available.
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