Article Text

Cardiovascular and neuropsychiatric safety of varenicline and bupropion compared with nicotine replacement therapy for smoking cessation: study protocol of a retrospective cohort study using the QResearch general practice database
  1. Daniel Kotz1,2,3,
  2. Colin Simpson3,
  3. Wolfgang Viechtbauer4,
  4. Onno C P van Schayck1,3,
  5. Robert West2,
  6. Aziz Sheikh1,3,5
  1. 1Department of Family Medicine, CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, The Netherlands
  2. 2Cancer Research UK Health Behaviour Research Centre, University College London, London, UK
  3. 3Allergy and Respiratory Research Group, Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK
  4. 4MHeNS School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
  5. 5Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Daniel Kotz; d.kotz{at}maastrichtuniversity.nl, http://www.daniel-kotz.de

Abstract

Introduction Cigarette smoking continues to be the leading cause of preventable death and is the main risk factor of major diseases such as chronic obstructive pulmonary disease (COPD). The best treatment to help smokers quit is a combination of behavioural support with pharmacotherapy. Varenicline is the newest drug on the market and has been shown to be effective in the general smoking population and in smokers with COPD. The safety profile of varenicline was initially established using standard approaches to pharmacovigilance, but postmarketing reports have raised concerns about a possible association between the use of varenicline and cardiovascular and neuropsychiatric events. Although recent studies have not confirmed such an association, further research is needed given the large number of smokers who are being prescribed varenicline, including important subgroups such as smokers with COPD who may be particularly vulnerable to side effects of drugs. The aim of this study is to assess the cardiovascular and neuropsychiatric safety of varenicline using data from the QResearch general practice (GP) database.

Methods and analysis We will conduct a retrospective cohort study in the QResearch GP database. Patients will be categorised into three exposure groups: prescription of (1) varenicline, (2) bupropion or (3) nicotine replacement therapy (NRT Rx; =reference group). We will separately consider major incident neuropsychiatric and cardiovascular outcomes that occur during 6 months of follow-up using Cox proportional hazards models, adjusted for confounders. Furthermore, propensity score analysis will be used as an analytical approach to account for potential confounding by indication.

Ethics and dissemination This work involves analysis of anonymised, routinely collected data. The protocol has been independently peer-reviewed by the QResearch Scientific Board and meets the requirements of the Trent research ethics committee. We plan to disseminate the results from this study via articles in international peer-reviewed journals and presentations at relevant national and international health conferences.

  • Epidemiology
  • Mental Health

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