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Effect of cytisine vs varenicline on smoking cessation: A randomized clinical trial


Courtney, RJ and McRobbie, H and Tutka, P and Weaver, NA and Mendelsohn, CP and Shakeshaft, A and Talukder, S and Macdonald, C and Thomas, D and Kwan, BCH and Walker, N and Gartner, C and Mattick, RP and Paul, C and Ferguson, SG and Zwar, NA and Richmond, RL and Doran, CM and Boland, VC and Hall, W and West, R and Farrell, M, Effect of cytisine vs varenicline on smoking cessation: A randomized clinical trial, JAMA Network Open, 326, (1) pp. 56-64. ISSN 2574-3805 (2021) [Refereed Article]

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Copyright 2021 American Medical Association

DOI: doi:10.1001/jama.2021.7621


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.

Item Details

Item Type:Refereed Article
Keywords:smoking cessation, tobacco, varenicline, cytisine
Research Division:Health Sciences
Research Group:Public health
Research Field:Preventative health care
Objective Division:Health
Objective Group:Public health (excl. specific population health)
Objective Field:Preventive medicine
UTAS Author:Ferguson, SG (Professor Stuart Ferguson)
ID Code:145115
Year Published:2021
Funding Support:National Health and Medical Research Council (1108318)
Web of Science® Times Cited:14
Deposited By:Medicine
Deposited On:2021-07-01
Last Modified:2021-09-02
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