Effect of Cytisine vs Varenicline on Smoking Cessation

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 PARTICIPANTSThis 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 MEASURESThe 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 ϱ]; 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.

Tobacco use disorder and cardiovascular health

“…Cytisine is a plant alkaloid that has nicotine-like effects, while at the same time blocking the effects of nicotine, similar to varenicline [86]. Clinical trials show efficacy comparable with other first-line smoking cessation medications, with relatively few adverse effects [87][88][89]. This drug is licensed in eastern Europe, but not in the United States or in many other countries.…”

Effectiveness, safety and cost-effectiveness of vaporized nicotine products versus nicotine replacement therapy for tobacco smoking cessation in a low-socioeconomic status Australian population: a study protocol for a randomized controlled trial

“…Participants from Sydney and the wider catchment region are recruited predominately through study advertisements across online and social media platforms such as Facebook advertisements. Participants in a recently completed clinical trial comparing cytisine versus varenicline for smoking cessation who consented to being contacted about future research and were receiving a government pension were also invited to take part [ 23 ].…”

Does Smoking Affect OSA? What about Smoking Cessation?

“…At low doses, cytisine activates nAChRs in the mesolimbic reward pathways and that inhibits nicotine’s sensory stimulation and limits the symptoms of withdrawal [ 103 ]. Cytisine was not only noninferior to NRT but had superior effectiveness [ 104 ]; however, in a recent study, varenicline was found more effective [ 105 ]. Varenicline is a partial α4β2 agonist that has all the characteristics of cytisine but is more efficient with fewer side effects [ 106 ].…”