Varenicline: mode of action, efficacy, safety and accumulated experience salient for clinical populations

Objective: Varenicline, a selective partial agonist of the α4β2 nicotinic acetylcholine receptor, is a smoking cessation pharmacotherapy that more than doubles the chance of quitting smoking at 6 months compared with placebo. This article reviews salient knowledge of the discovery, pharmacological characteristics, and the efficacy and safety of varenicline in general and in specific populations of smokers and provides recommendations to support use in clinical practice. Methods: Literature searches for varenicline were conducted using PubMed, with date limitations of 2000–2018 inclusive, using search terms covering the discovery, mechanism of action, pharmacokinetics, efficacy and safety in different populations of smokers, alternative quit approaches and combination therapy. Selection of safety and efficacy data was limited to clinical trials, meta-analyses and observational studies. Results: Standard administration of varenicline is efficacious in helping smokers to quit, including smokers with cardiovascular disease and chronic obstructive pulmonary disease. Furthermore, varenicline efficacy may be improved with pre-loading, a gradual quitting approach for smokers unwilling or unable to quit abruptly, and extended treatment in smokers who have recently quit to help maintain abstinence. Initial concerns regarding the association of varenicline with increased risk of neuropsychiatric and cardiovascular adverse events have been disproven after extensive clinical evaluations, and the benefit-risk profile of varenicline is considered favorable. Conclusions: Varenicline is efficacious and safe for all adult smokers with a range of clinical characteristics. Evidence suggests that approaches offering greater flexibility in timing and duration of treatment may further extend treatment efficacy and clinical reach.

研究目的：伐尼克兰（Varenicline）是α4β2烟碱型乙酰胆碱受体（α4β2 nicotinic acetylcholine receptor）的选择性部分激动剂，作为戒烟药物疗法，其可使吸烟者6个月时的戒烟成功率较安慰剂组提升一倍以上。本文综述了伐尼克兰的研发历程、药理学特性、针对普通及特定人群吸烟者的疗效与安全性等核心研究成果，并为其临床应用提供指导建议。研究方法：通过PubMed数据库开展伐尼克兰相关文献检索，检索时限为2000年至2018年（含首尾两年），检索词涵盖其研发背景、作用机制、药代动力学、不同人群吸烟者中的疗效与安全性、替代戒烟方案及联合治疗方案。所纳入的安全性与有效性数据仅限临床试验、荟萃分析（meta-analyses）及观察性研究（observational studies）。研究结果：标准给药方案下，伐尼克兰可有效帮助吸烟者戒烟，包括合并心血管疾病与慢性阻塞性肺疾病的吸烟者。此外，对于不愿或无法骤然戒烟的人群，采用预负荷给药联合渐进式戒烟法，或为近期戒烟者提供延长治疗以维持戒断状态，均可进一步提升伐尼克兰的戒烟疗效。此前有关伐尼克兰会增加神经精神及心血管不良事件风险的担忧，经大规模临床评估后已被证实不成立，伐尼克兰的获益-风险特征被认为较为有利。研究结论：伐尼克兰对具备各类临床特征的成年吸烟者均具有良好的疗效与安全性。现有证据表明，在治疗时机与疗程上具备更高灵活性的方案，可进一步提升其治疗效果并扩大临床应用范围。