Date Published: February 20, 2018
Publisher: John Wiley and Sons Inc.
Author(s): Neil M. Davies, Gemma M. J. Taylor, Amy E. Taylor, Timothy Jones, Richard M. Martin, Marcus R. Munafò, Frank Windmeijer, Kyla H. Thomas.
To investigate whether smokers prescribed varenicline had lower risks of serious ill‐health during the 4 years following treatment compared with those prescribed nicotine replacement therapy (NRT).
Observational cohort study of electronic medical records.
A total of 370 UK general practices sampled from the Clinical Practice Research Datalink.
A total of 126 718 patients aged 18 and over who were issued smoking cessation prescriptions between 1 September 2006 and 31 March 2014.
Our primary outcome was all‐cause mortality within 2 years of first prescription as indicated by linked Office of National Statistics data. Our secondary outcomes were cause‐specific mortality, all‐cause, cause‐specific hospitalization, primary care diagnosis of myocardial infarction or chronic obstructive pulmonary disease (COPD), body mass index and attendance rate to primary care within 2 years of first prescription. Risk differences and 95% confidence intervals were estimated by multivariable adjusted regression and propensity score matched regression. We used instrumental variable analysis to overcome residual confounding.
People prescribed varenicline were healthier at baseline than those prescribed NRT in almost all characteristics, highlighting the potential for residual confounding. Our instrumental variable analysis results found that people prescribed varenicline had a similar risk of mortality at 2 years [risk difference per 100 patients treated = 0.67, 95% confidence interval (CI) = ‐0.11 to 1.46)] to those prescribed NRT, and there were similar rates of all‐cause hospitalization, incident primary‐care diagnoses of myocardial infarction and COPD. People prescribed varenicline subsequently attended primary care less frequently.
Smokers prescribed varenicline in primary care in the United Kingdom do not appear to be less likely to die, be hospitalized or experience a myocardial infarction or chronic obstructive pulmonary disease during the following 2 years compared with smokers prescribed nicotine replacement therapy, but they gain more weight and attend primary care less frequently.
Meta‐analyses of randomized controlled trials (RCTs) have shown that five additional smokers will quit for every 100 smokers allocated to varenicline rather than nicotine replacement therapy (NRT) 1. These meta‐analyses have also shown that patients allocated to varenicline are unlikely to be at increased risk of short‐term neuropsychiatric or cardiovascular adverse events 2, 3. Both randomized trials and observational studies have suggested that patients prescribed varenicline are less likely to smoke in the short term 4, 5. These reductions in smoking should translate into health benefits in the years following treatment. However, we have relatively little evidence about the effects of prescribing varenicline in primary care on health outcomes in the years following treatment.
We conducted a prospective cohort study of all people prescribed varenicline or NRT in a sample of primary care practices in the United Kingdom. All hypotheses and analyses were pre‐specified and a study protocol was published 10. The CPRD’s terms and conditions for accessing the data do not allow us to disseminate individual level patient data. However, researchers interested in accessing the data should contact the CPRD directly (firstname.lastname@example.org). The statistical code used to produce these results can be accessed online (https://github.com/nmdavies/varenicline-safety/). The study is registered at clinicaltrials.gov (NCT: NCT02681848) and the Open Science Framework (https://osf.io/g9ch2/).
We found little evidence that patients prescribed varenicline versus NRT had a lower risk of mortality, hospitalization or primary care diagnosis of myocardial infarction or chronic obstructive pulmonary disease 2 years after first prescription. Both multivariable adjusted and instrumental variable regression suggested that patients prescribed varenicline attended primary care less frequently during the 2 years following the first prescription.
All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf. We declare the following interests: M.R.M. reports grants from Pfizer, grants from Rusan, and non‐financial support from GlaxoSmithKline, outside the submitted work; A.E.T. reports a grant from the Global Research Awards for Nicotine Dependence, which is an Independent Competitive Grants Program supported by Pfizer. R.M.M. was a member of the Independent Scientific Advisory Committee of the Medicines and Healthcare products Regulatory Agency which approves applications for CPRD studies. All other authors report no other relationships or activities that could appear to have influenced the submitted work.