澳大利亚新南威尔士大学Michael Farrell团队比较了金雀花碱和瓦伦克林对戒烟的影响。2021年7月6日出版的《美国医学会杂志》发表了这项成果。

金雀花碱在戒烟方面比安慰剂和尼古丁替代疗法更有效。然而，金雀花碱是否优于最有效的戒烟药物瓦伦克林尚不清楚，瓦伦克林与已知的导致停止治疗的不良事件相关。

为了检验标准金雀花碱治疗（25 天）是否至少与标准瓦伦克林治疗（84 天）一样有效，2017年11月至2019年5月，研究组在澳大利亚进行了一项双盲、非劣效性、开放标签、随机临床试验；随访于2020年1月完成。研究组共招募了1452名愿意尝试戒烟的澳大利亚每日吸烟成人。数据收集主要通过计算机辅助电话采访进行，但也进行了面对面访问以验证主要结果。

研究组将参与者随机分组，根据制造商的推荐剂量提供治疗，其中725名接受金雀花碱治疗，在25天的疗程中逐渐减少药量；727名接受瓦伦克林治疗，共持续84天。所有参与者都得到了标准的电话行为支持。主要结局为在7个月的随访中使用一氧化碳呼气试验证实的6个月连续戒断，非劣效性边缘设置为 5%。

1452名参与者的平均年龄为42.9岁，51.1%为女性，共有1108名（76.3%）完成了试验。金雀花碱组经验证的6个月连续戒断率为11.7%，瓦伦克林组为 13.3%。金雀花碱组482名参与者共发生997起自我报告的不良事件，瓦伦克林组510名参与者中有1206起，两组发生率之比为0.88。

研究结果表明，在愿意戒烟的每日吸烟者中，金雀花碱治疗25天与瓦伦克林治疗84天，在戒烟方面并未表现出非劣势性。

附：英文原文

Title: Effect of Cytisine vs Varenicline on Smoking Cessation: A Randomized Clinical Trial

Author: Ryan J. Courtney, Hayden McRobbie, Piotr Tutka, Natasha A. Weaver, Dennis Petrie, Colin P. Mendelsohn, Anthony Shakeshaft, Saki Talukder, Christel Macdonald, Dennis Thomas, Benjamin C. H. Kwan, Natalie Walker, Coral Gartner, Richard P. Mattick, Christine Paul, Stuart G. Ferguson, Nicholas A. Zwar, Robyn L. Richmond, Christopher M. Doran, Veronica C. Boland, Wayne Hall, Robert West, Michael Farrell

Issue&Volume: 2021/07/06

Abstract:

Importance  Cytisine is more effective than placebo and nicotine replacement therapy for smoking cessation. However, cytisine has not been tested against the most effective smoking cessation medication, varenicline, which is associated with adverse events known to lead to discontinuation of therapy.

Objective  To examine whether standard cytisine treatment (25 days) was at least as effective as standard varenicline treatment (84 days) for smoking cessation.

Design, Setting, and Participants  This noninferiority, open-label randomized clinical trial with allocation concealment and blinded outcome assessment was undertaken in Australia from November 2017 through May 2019; follow-up was completed in January 2020. A total of 1452 Australian adult daily smokers willing to make a quit attempt were included. Data collection was conducted primarily by computer-assisted telephone interview, but there was an in-person visit to validate the primary outcome.

Interventions  Treatments were provided in accordance with the manufacturers’ recommended dosage: cytisine (n=725), 1.5-mg capsules taken 6 times daily initially then gradually reduced over the 25-day course; varenicline (n=727), 0.5-mg tablets titrated to 1 mg twice daily for 84 days (12 weeks). All participants were offered referral to standard telephone behavioral support.

Main Outcomes and Measures  The primary outcome was 6-month continuous abstinence verified using a carbon monoxide breath test at 7-month follow-up. The noninferiority margin was set at 5% and the 1-sided significance threshold was set at .025.

Results  Among 1452 participants who were randomized (mean [SD] age, 42.9 [12.7] years; 742 [51.1%] women), 1108 (76.3%) completed the trial. Verified 6-month continuous abstinence rates were 11.7% for the cytisine group and 13.3% for the varenicline group (risk difference, 1.62% [1-sided 97.5% CI, 5.02% to ∞]; P=.03 for noninferiority). Self-reported adverse events occurred less frequently in the cytisine group (997 events among 482 participants) compared with the varenicline group (1206 events among 510 participants) and the incident rate ratio was 0.88 (95% CI, 0.81 to 0.95; P=.002).

Conclusions and Relevance  Among daily smokers willing to quit, cytisine treatment for 25 days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiority regarding smoking cessation.

DOI: 10.1001/jama.2021.7621

Source: https://jamanetwork.com/journals/jama/article-abstract/2781643