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

IMPORTANCE: Cytisine is more effective than placebo and nicotine replacement therapy forsmoking cessation. However, cytisine has not been tested against the most effective smokingcessation medication, varenicline, which is associated with adverse events known to lead todiscontinuation of therapy.OBJECTIVE: To examine whether standard cytisine treatment (25 days) was at least aseffective as standard varenicline treatment (84 days) for smoking cessation.DESIGN, SETTING, AND PARTICIPANTS: This noninferiority, open-label randomized clinical trialwith allocation concealment and blinded outcome assessment was undertaken in Australiafrom November 2017 through May 2019; follow-up was completed in January 2020. A totalof 1452 Australian adult daily smokers willing to make a quit attempt were included. Datacollection was conducted primarily by computer-assisted telephone interview, but there wasan 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 thengradually reduced over the 25-day course; varenicline (n = 727), 0.5-mg tablets titrated to1 mg twice daily for 84 days (12 weeks). All participants were offered referral to standardtelephone behavioral support.MAIN OUTCOMES AND MEASURES: The primary outcome was 6-month continuous abstinenceverified using a carbon monoxide breath test at 7-month follow-up. The noninferiority marginwas 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 continuousabstinence rates were 11.7% for the cytisine group and 13.3% for the varenicline group (riskdifference, −1.62% [1-sided 97.5% CI, −5.02% to ]; P = .03 for noninferiority). Self-reportedadverse events occurred less frequently in the cytisine group (997 events among 482participants) compared with the varenicline group (1206 events among 510 participants) andthe 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 25days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiorityregarding smoking cessation