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Comparative Safety of Long-Acting Inhaled Bronchodilators

A Cohort Study Using the UK THIN Primary Care Database

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Abstract

Background: Use of a long-acting inhaled bronchodilator, either an anticholinergic or a β-adrenergic receptor agonist (β-agonist), is recommended for maintenance treatment of chronic obstructive pulmonary disease (COPD). In COPD, the organ system most frequently requiring medical care, other than the respiratory system, is the cardiac system.

Objectives: To compare the risk of total mortality and certain respiratory and cardiac adverse events among users of the two types of recommended long-acting bronchodilators, we conducted a cohort study. Specifically, the study compared the safety of the only approved long-acting anticholinergic, tiotropium bromide, with the single-ingredient long-acting β-agonists (LABAs) salmeterol or formoterol in a broad population of users.

Methods: We used automated general practitioner data from the UK THIN (The Health Information Network) database as the data source for this study. We used Cox proportional hazards models to compute hazard ratio (HR) estimates and 95% CI controlling for propensity scores comprising various baseline demographic variables, medical therapies and illnesses.

Results: The 1061 tiotropium users and 1801 LABA users were similar with regard to risk of total mortality (HR 0.93; 95% CI 0.59, 1.44) and most cardiac events, including angina (HR 0.77; 95% CI 0.37, 1.59), atrial fibrillation or flutter (HR 0.60; 95% CI 0.25, 1.42), myocardial infarction (HR 1.29; 95% CI 0.45, 3.66) and tachycardia (HR 0.66; 95% CI 0.29, 1.51). Though imprecise, there was evidence of a decreased risk of heart failure (HR 0.65; 95% CI 0.37, 1.12) in tiotropium users. As regards respiratory endpoints, the risk of COPD exacerbation (HR 1.15; 95% CI 0.79, 1.67) and pneumonia (HR 1.11; 95% CI 0.38, 3.26) were similar among users of each type of drug, although there was a decreased risk of asthma exacerbation (HR 0.41; 95% CI 0.26, 0.64) in tiotropium users compared with LABA users.

Conclusions: Users of tiotropium and single-ingredient LABA had similar risk of total mortality and cardiovascular endpoints. The decreased risk of asthma exacerbations with tiotropium may be due to residual confounding by indication. Confidence limits for most events include reduced risks for tiotropium and also small increases in risk. Nevertheless, the point estimates suggest that tiotropium was associated with a lower risk of each cardiac event except myocardial infarction. However, the small number of cases means that further studies are needed to confirm these results.

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  1. 1The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

This study was funded by Boehringer Ingelheim Pharmaceuticals Incorporated. Michele Jara, Steven Kesten and Stephan F. Lanes are employees of Boehringer Ingelheim. Charles Wentworth III and Corey May are consultants for Boehringer Ingelheim. The authors were responsible for all aspects of this study, including design, analysis and interpretation.

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Authors and Affiliations

  1. Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, Connecticut, 06877-0368, USA

    Michele Jara, Stephan F. Lanes & Steven Kesten

  2. Analytic Consulting Solutions Inc., Warwick, Rhode Island, USA

    Charles Wentworth III & Corey May

Authors
  1. Michele Jara
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  2. Stephan F. Lanes
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  3. Charles Wentworth III
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  4. Corey May
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  5. Steven Kesten
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Correspondence to Michele Jara.

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Jara, M., Lanes, S.F., Wentworth, C. et al. Comparative Safety of Long-Acting Inhaled Bronchodilators. Drug-Safety 30, 1151–1160 (2007). https://doi.org/10.2165/00002018-200730120-00007

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