Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Bristol Medical School, University of Bristol, Bristol, UK.
Health Technol Assess. 2020 Feb;24(9):1-46. doi: 10.3310/hta24090.
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.
To estimate the effect of prescribing varenicline on smoking cessation rates and health outcomes.
Clinical Practice Research Datalink.
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.
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.
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 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.
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.
This trial is registered as NCT02681848.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 9. See the NIHR Journals Library website for further project information.
吸烟是导致疾病和过早死亡的主要可避免原因。戒烟的一线治疗方法是尼古丁替代疗法和伐伦克林。实验研究的荟萃分析表明，与接受尼古丁替代疗法治疗的参与者相比，接受伐伦克林治疗的参与者在治疗后 6 个月内戒烟的可能性高出 1.57 倍（95%置信区间为 1.29 至 1.91 倍）。然而，关于在初级保健中开处方伐伦克林的有效性的证据有限。我们调查了这些药物在普通人群中的有效性和不良事件发生率。
评估开处方伐伦克林对戒烟率和健康结果的影响。
临床实践研究数据链接。
我们使用临床实践研究数据链接中的电子病历进行了一项观察性队列研究。我们从 2006 年 9 月 1 日起提取了所有接受伐伦克林或尼古丁替代疗法治疗且年龄≥18 岁的患者的数据。我们调查了伐伦克林对戒烟、全因死亡率和特定原因死亡率以及以下疾病住院治疗的影响：（1）慢性肺部疾病，（2）肺癌，（3）冠心病，（4）肺炎，（5）脑血管疾病，（6）糖尿病和（7）外部原因；初级保健诊断的心肌梗死、慢性阻塞性肺疾病、抑郁症或焦虑症处方；体重（公斤）；全科医生和医院就诊。我们的主要结局是首次处方后 2 年的戒烟情况。我们调查了开处方伐伦克林的患者与开处方尼古丁替代疗法的患者之间的基线差异。我们使用多变量调整、倾向评分和工具变量回归报告结果。最后，我们开发了评估我们使用的不同统计方法的相对偏差的方法。
与接受尼古丁替代疗法治疗的患者相比，接受伐伦克林治疗的患者在几乎所有特征上都更健康，这突显了潜在的残余混杂。我们的工具变量分析结果发现，与接受尼古丁替代疗法治疗的患者相比，接受伐伦克林治疗的患者在首次处方后 2 年内死亡率较低的证据很少（风险差异 0.67，95%置信区间为-0.11 至 1.46）。他们有相似的全因住院率、原发性护理诊断的心肌梗死和慢性阻塞性肺疾病。接受伐伦克林治疗的患者随后到初级保健的就诊频率较低。与接受尼古丁替代疗法治疗的患者相比，接受伐伦克林治疗的患者在治疗后 6 个月时更有可能（比值比 1.46，95%置信区间为 1.42 至 1.50）戒烟。来自较贫困地区的患者不太可能被开处方伐伦克林。然而，伐伦克林对这些群体的疗效相似。
在初级保健中开处方伐伦克林的患者比开处方尼古丁替代疗法的患者更有可能戒烟，但几乎没有证据表明他们在首次处方后的 4 年内死亡率或发病率较低。人群中疗效的异质性很小。
未来的研究应该调查戒烟产品处方的下降情况；制定戒烟的最佳治疗方案；使用生存结果的工具方法；并开发比较多变量调整和工具变量估计的方法。
并非我们的所有代码列表都经过验证，体重指数和指数的多重剥夺都有缺失值，我们的结果可能会受到残余混杂的影响，并且我们没有关于治疗依从性的信息。
本试验由英国国家卫生研究所（NIHR）卫生技术评估计划资助，并将在 ; 第 24 卷，第 9 期全文发表。请访问 NIHR 期刊库网站以获取进一步的项目信息。
