Varenicline versus nicotine replacement therapy for long-term smoking cessation: an observational study using the Clinical Practice Research Datalink

Abstract

Background Smoking is the leading avoidable cause of illness and premature mortality. The first-line treatments for smoking cessation are nicotine replacement therapy and varenicline. Meta-analyses of experimental studies have shown that participants allocated to the varenicline group were 1.57 times (95% confidence interval 1.29 to 1.91 times) as likely to be abstinent 6 months after treatment as those allocated to the nicotine replacement therapy group. However, there is limited evidence about the effectiveness of varenicline when prescribed in primary care. We investigated the effectiveness and rate of adverse events of these medicines in the general population. Objective To estimate the effect of prescribing varenicline on smoking cessation rates and health outcomes. Data sources Clinical Practice Research Datalink. Methods We conducted an observational cohort study using electronic medical records from the Clinical Practice Research Datalink. We extracted data on all patients who were prescribed varenicline or nicotine replacement therapy after 1 September 2006 who were aged ≥ 18 years. We investigated the effects of varenicline on smoking cessation, all-cause mortality and cause-specific mortality and hospitalisation for: (1) chronic lung disease, (2) lung cancer, (3) coronary heart disease, (4) pneumonia, (5) cerebrovascular disease, (6) diabetes, and (7) external causes; primary care diagnosis of myocardial infarction, chronic obstructive pulmonary disease, depression, or prescription for anxiety; weight in kg; general practitioner and hospital attendance. Our primary outcome was smoking cessation 2 years after the first prescription. We investigated the baseline differences between patients prescribed varenicline and patients prescribed nicotine replacement therapy. We report results using multivariable-adjusted, propensity score and instrumental variable regression. Finally, we developed methods to assess the relative bias of the different statistical methods we used. Results People prescribed varenicline were healthier at baseline than those prescribed nicotine replacement therapy in almost all characteristics, which highlighted the potential for residual confounding. Our instrumental variable analysis results found little evidence that patients prescribed varenicline had lower mortality 2 years after their first prescription (risk difference 0.67, 95% confidence interval –0.11 to 1.46) than those prescribed nicotine replacement therapy. They had similar rates of all-cause hospitalisation, incident primary care diagnoses of myocardial infarction and chronic obstructive pulmonary disease. People prescribed varenicline subsequently attended primary care less frequently. Patients prescribed varenicline were more likely (odds ratio 1.46, 95% confidence interval 1.42 to 1.50) to be abstinent 6 months after treatment than those prescribed nicotine replacement therapy when estimated using multivariable-adjusted for baseline covariates. Patients from more deprived areas were less likely to be prescribed varenicline. However, varenicline had similar effectiveness for these groups. Conclusion Patients prescribed varenicline in primary care were more likely to quit smoking than those prescribed nicotine replacement therapy, but there was little evidence that they had lower rates of mortality or morbidity in the 4 years following the first prescription. There was little evidence of heterogeneity in effectiveness across the population. Future work Future research should investigate the decline in prescribing of smoking cessation products; develop an optimal treatment algorithm for smoking cessation; use methods for using instruments with survival outcomes; and develop methods for comparing multivariable-adjusted and instrumental variable estimates. Limitations Not all of our code lists were validated, body mass index and Index of Multiple Deprivation had missing values, our results may suffer from residual confounding, and we had no information on treatment adherence. Trial registration This trial is registered as NCT02681848. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 9. See the NIHR Journals Library website for further project information.

Time trends in access to smoking cessation support for people with depression or severe mental illness: a cohort study in English primary care

“…Rates of prescribing of varenicline and bupropion were very low overall, and even lower for those with SMI, despite good evidence of effectiveness of both drugs in those with SMI in increasing medium-long term quit rates37 38 and some evidence that varenicline may be more effective than NRT 39 40. Low prescribing probably reflects concerns among GPs and patients regarding the side effects of these two drugs during this period.…”

Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Type 2 Diabetes

“…The sample size calculation for this RCT was based on quit rates from previous smoking cessation studies. 17,33,34 We computed that 174 patients (87 per study group) were required to have 90% power with a 2-sided α error rate of .05 to detect a difference of at least 18.7% between treatment groups in CAR at weeks 9 to 24. Allowing for a conservative attrition rate of approximately 40%, the target number of participants was increased to a total of 300 (150 per each study group).…”

“…Summary statistics were provided for each treatment group. At baseline, differences in primary end point (CAR at weeks [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] between varenicline and placebo groups were evaluated by means of 1-way analysis of variance for normally distributed continuous variables and by Mann-Whitney test for not normally distributed continuous variables. The χ 2 test was used for categorical variables, and differences in primary end point were evaluated by means of χ 2 test.…”

“…Completion of the treatment phase (visits 2-13) was followed by the nontreatment phase (visits [14][15][16][17][18]. Only patients who completed their treatment schedule were invited to the nontreatment follow-up phase.…”

“…9,14 Randomized clinical trials (RCTs) have indicated that varenicline is more efficacious for smoking cessation than placebo, bupropion, 15,16 or nicotine replacement therapy. 17 Varenicline has been shown to be efficacious also in smokers with cardiovascular disease, 18 chronic obstructive pulmonary disease, 19 or depressive disorders. 20 The efficacy and safety of varenicline in smokers with diabetes have not been extensively studied, however.…”