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Cardiovascular and neuropsychiatric risks of varenicline and bupropion in smokers with chronic obstructive pulmonary disease
  1. Daniel Kotz1,2,3,4,
  2. Wolfgang Viechtbauer5,
  3. Colin R Simpson3,
  4. Onno C P van Schayck2,3,
  5. Robert West4,
  6. Aziz Sheikh2,3,6
  1. 1Addiction Research and Clinical Epidemiology Unit, Medical Faculty of the Heinrich-Heine, Institute of General Practice, University Düsseldorf, Düsseldorf, Germany
  2. 2Department of Family Medicine, CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, The Netherlands
  3. 3Allergy & Respiratory Research Group, Centre for Medical Informatics, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK
  4. 4Cancer Research UK Health Behaviour Research Centre, University College London, London, UK
  5. 5MHeNS School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
  6. 6Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Professor Daniel Kotz, Addiction Research and Clinical Epidemiology Unit, Medical Faculty of the Heinrich-Heine, University Düsseldorf, Institute of General Practice, Düsseldorf 40225, Germany; Daniel.Kotz{at}


Background Varenicline and bupropion are effective smoking cessation treatments, but there are concerns about their safety in smokers with COPD.

Objective To investigate whether varenicline and bupropion are associated with serious adverse cardiovascular and neuropsychiatric events in smokers with COPD.

Methods In a retrospective cohort study, we used data from 14 350 patients with COPD included in the QResearch database, which holds data from 753 National Health Service general practices across England. We identified patients with COPD who received a prescription of nicotine replacement therapy (NRT; N=10 426; reference group), bupropion (N=350) or varenicline (N=3574) in the period between January 2007 and June 2012. Patients were followed up for 6 months to compare incident cardiovascular (ie, ischaemic heart disease, stroke, heart failure, peripheral vascular disease and cardiac arrhythmias) and neuropsychiatric (ie, depression and self-harm) events using Cox proportional hazards models, adjusted for potential confounders. Propensity score analysis was used as an additional approach to account for potential confounding by indication. We also modelled the effects of possible unmeasured confounders.

Results Neither bupropion nor varenicline showed an increased risk of adverse events compared with NRT. Varenicline was associated with a significantly reduced risk of heart failure (HR=0.56, 95% CI 0.34 to 0.92) and depression (HR=0.73, 95% CI 0.61 to 0.86). Similar results were obtained from the propensity score analysis. Modelling of unmeasured confounding provided additional evidence that an increased risk of these adverse events was very unlikely.

Conclusion In smokers with COPD, varenicline and bupropion do not appear to be associated with an increased risk of cardiovascular events, depression or self-harm in comparison with NRT.

  • COPD Pharmacology
  • Smoking cessation
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  • Contributors DK had the original idea for this study, drafted its funding application and this article. He had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. WV and DK wrote the statistical script and analysed the data. All authors contributed to the conception and design of the study, revised the article and gave final approval of the version to be published.

  • Funding QInnovation Award (provided by the software provider EMIS and the University of Nottingham) with additional support from the Ministry for Innovation, Science and Research of the German Federal State of North Rhine-Westphalia (“NRW-Rückkehrprogramm)”, Cancer Research UK, the Medical Research Council and The Commonwealth Fund. The funder provided access to the QResearch database, which included collection and management of data. The funder was not involved with the design and conduct of the study; analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

  • Competing interests DK received an unrestricted grant from Pfizer for an investigator-initiated trial on the effectiveness of practice nurse counselling and varenicline for smoking cessation in primary care (Dutch Trial Register NTR3067). RW received grants, personal fees and non-financial support from Pfizer, GSK and J&J and personal fees from Novartis. OCPvS received an unrestricted research grant from Pfizer. None of this funding was directly related to this study. Furthermore, the manufacturers of varenicline and bupropion were not involved during any stage of this project. DK was supported by a research grant (“NRW-Rückkehrprogramm)” from the Ministry for Innovation, Science and Research of the German Federal State of North Rhine-Westphalia. AS was supported by the Farr Institute, which is supported by a consortia of funders led by the Medical Research Council and The Commonwealth Fund, a private independent foundation based in New York City; the views presented here are those of the author and not necessarily those of The Commonwealth Fund, its directors, officers or staff.

  • Ethics approval Our protocol was independently peer reviewed by the QResearch Scientific Board and satisfied the requirements of the Trent research ethics committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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