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Original Research |

Long-acting bronchodilator initiation in COPD and the risk of adverse cardio-pulmonary events: A population-based comparative safety study

Samy Suissa; Sophie Dellaniello; Pierre Ernst
Author and Funding Information

Competing Interests: Dr. Suissa has received research grants from Boehringer Ingelheim and has participated in advisory board meetings or as speaker for AstraZeneca, Boehringer-Ingelheim, Novartis, and Pfizer. Dr. Ernst and Ms Dell’Aniello do not have any conflicts of interest to disclose.

Take home message: COPD treatment initiation with tiotropium does not increase cardiovascular risk versus LABAs, but reduces pneumonia risk.

Centre for Clinical Epidemiology, Lady Davis Institute - Jewish General Hospital, Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada

Please address correspondence and request for reprints to: Dr. Samy Suissa, Centre for Clinical Epidemiology, Jewish General Hospital, 3755 Cote Ste-Catherine, H-461, Montreal, Québec, Canada H3T 1E2.


Copyright 2016, . All Rights Reserved.


Chest. 2016. doi:10.1016/j.chest.2016.08.001
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Abstract

Background  Long-acting bronchodilators, including long-acting beta2-agonists (LABA) and the anticholinergic tiotropium, are recommended as initial maintenance therapy in COPD. Studies to date have been limited in size and reported ambivalent results on the comparative risk of cardiovascular, cerebrovascular and pulmonary adverse events between these two long-acting bronchodilators. Moreover, little information is available for the period when treatment is first initiated, a time when subjects may be especially at risk.

Methods  We identified a cohort of new users of long-acting bronchodilators during 2002-2012, age 55 or older, from the United Kingdom’s Clinical Practice Research Datalink. Patients initiating tiotropium were matched on high-dimensional propensity scores and prior inhaled corticosteroid use with patients initiating LABAs, and followed for one year for the occurrence of acute myocardial infarction (AMI), stroke, heart failure, arrhythmia and pneumonia.

Results  26,442 tiotropium initiators were matched to 26,442 LABA initiators, mainly single inhalers combined with inhaled corticosteroids. The hazard ratio (HR) of AMI associated with tiotropium initiation, relative to LABA initiation, was 1.10 (95% CI: 0.88-1.38), while for stroke it was 1.02 (95% CI: 0.78-1.34), for arrhythmia 0.81 (95% CI: 0.60-1.09), and heart failure 0.90 (95% CI: 0.79-1.02). The incidence of pneumonia was significantly less with tiotropium (HR 0.81; 95% CI: 0.72-0.92).

Conclusion  COPD treatment initiation with tiotropium compared with LABA does not increase cardiovascular risk in the first year of treatment. The risk of pneumonia is higher with LABA, a likely effect of the inhaled corticosteroids present in many LABA inhalers used in real world clinical practice.


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