Abstract
BACKGROUND AND AIMS: Varenicline and nicotine replacement therapy (NRT) are the most commonly used medications to quit smoking. Given their widespread use, monitoring adverse risks remains important. This study aimed to estimate the neuropsychiatric and cardiovascular risks associated with varenicline and NRT as used in routine UK care.
DESIGN: Case crossover study.
SETTING: UK based electronic primary care records in the Clinical Practice Research Datalink from 2006 to 2015 linked to hospital and mortality datasets.
PARTICIPANTS: Adult smokers (n=?) observed in periods when exposed and not exposed to either varenicline or NRT.
MEASUREMENTS: Main outcomes included suicide, self-harm, myocardial infarction (MI), all-cause death and cause-specific death (MI, chronic obstructive pulmonary disease (COPD)). In primary analyses, conditional logistic regression was used to compare the chance of varenicline or NRT exposure in the risk period (90 days prior to the event) with the chance of exposure in an earlier single reference period (91-180 days prior to the event) or multiple 90-day reference periods to increase statistical power.
FINDINGS: In the primary analyses, findings were inconclusive for the associations between varenicline and the main outcomes using a single reference period, whilst NRT was associated with MI (Odds ratio (OR) 1.40, 95% Confidence interval (CI) 1.18-1.67). Using multiple reference periods, varenicline was associated with an increased risk of self-harm (OR 1.32, 95% CI 1.12-1.56) and suicide (OR 3.56, 95% CI 1.32-9.60) but a reduction in all-cause death (OR 0.75, 95% CI 0.61-0.93). NRT was associated with MI (OR 1.54, 95% CI 1.36-1.74), self-harm (OR 1.30, 95% CI 1.18-1.44), and deaths from MI (OR 1.53, 95% CI 1.11-2.10), COPD (OR 1.33, 95% CI 1.14-1.56) and all causes (OR 1.28, 95% CI 1.18-1.40) when using multiple reference periods.
CONCLUSIONS: There appear to be positive associations between 1) nicotine replacement therapy (NRT) and myocardial infarction, death, and risk of self-harm and 2) varenicline and increased risk of self-harm and suicide, as well as a negative association between varenicline and all-cause death. The associations may not be causal. They may reflect health changes at the time of smoking cessation (NRT is prescribed for people with cardiac problems) or be associated with quit attempts (exposure to both medicines was associated with self-harm).
| Original language | English |
|---|---|
| Pages (from-to) | 1532-1545 |
| Journal | Addiction |
| Volume | 116 |
| Issue number | 6 |
| Early online date | 16 Nov 2020 |
| DOIs | |
| Publication status | Published - 30 Jun 2021 |
Bibliographical note
This article is protected by copyright. All rights reserved.Funding
All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: K.H.T. received funding for the project from the Academy of Medical Sciences Starter Grant for Clinical Lecturers Scheme (supported by the Wellcome Trust, British Heart Foundation, Medical Research Council, Versus Arthritis, Prostate Cancer UK and the Royal College of Physicians). A.T. has received a Global Research Award for Nicotine Dependence (GRAND), an independently reviewed, competitive grants programme supported by Pfizer, to the University of Bristol. I.J.D. is supported by an unrestricted grant from GlaxoSmithKline and holds shares in GlaxoSmithKline. K.H.T. is currently funded by a National Institute for Health Research Postdoctoral Fellowship (PDF‐2017‐10‐068). Part of this work was undertaken while K.H.T. was funded by a clinical lectureship from the National Institute for Health Research. N.M.D. is supported by a Norwegian Research Council Grant Number 295989. G.T. is funded by a Cancer Research UK Population Researcher Postdoctoral Fellowship award (reference: C56067/A21330). I.J.D. is funded by an unrestricted grant from GlaxoSmithKline. R.M.M., D.G. and A.T. are supported by the NIHR Bristol Biomedical Research Centre, a partnership between the University Hospitals Bristol NHS Foundation Trust and University of Bristol. R.M.M. is also supported by a Cancer Research UK programme grant (C18281/A19169). G.T. and N.D. have received a Global Research Award for Nicotine Dependence (GRAND), an independently reviewed, competitive grants programme supported by Pfizer, to the University of Bristol. This project was supported by the Academy of Medical Sciences Starter Grant for Clinical Lecturers Scheme, which is supported by the Wellcome Trust, the Medical Research Council, the British Heart Foundation, Versus Arthritis, Prostate Cancer UK and the Royal College of Physicians. In the Declaration of Interests it states see below All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: K.H.T. received funding for the project from the Academy of Medical Sciences Starter Grant for Clinical Lecturers Scheme (supported by the Wellcome Trust, British Heart Foundation, Medical Research Council, Versus Arthritis, Prostate Cancer UK and the Royal College of Physicians).
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This is the peer reviewed version of the following article: Thomas, K. H., Davies, N. M., Taylor, A. E., Taylor, G. M. J., Gunnell, D., Martin, R. M., and Douglas, I. (2020) Risk of neuropsychiatric and cardiovascular adverse events following treatment with varenicline and nicotine replacement therapy in the UK Clinical Practice Research Datalink: a case‐crossover study. Addiction, , which has been published in final form at https://doi.org/10.1111/add.15338. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.