Cytisine versus varenicline for smoking cessation in New Zealand indigenous Māori: a randomized controlled trial

Abstract

Aim: To determine whether cytisine was at least as effective as varenicline in supporting smoking abstinence for ≥ 6 months in New Zealand indigenous Māori or whānau (extended-family) of Māori, given the high smoking prevalence in this population.

Design: Pragmatic, open-label, randomized, community-based non-inferiority trial.

Setting: Bay of Plenty, Tokoroa and Lakes District Health Board regions of New Zealand.

Participants: Adult daily smokers who identified as Māori or whānau of Māori, were motivated to quit in the next 2 weeks, were aged ≥ 18 years and were eligible for subsidized varenicline. Recruitment used multi-media advertising.

Interventions: A total of 679 people were randomly assigned (1 : 1) to receive a prescription for 12 weeks of cytisine or varenicline, plus low-intensity cessation behavioural support from the prescribing doctor and community stop-smoking services or a research assistant. Day 5 of treatment was the designated quit date.

Measurements: The primary outcome was carbon monoxide-verified continuous abstinence at 6 months, analysed as intention-to-treat (with multiple imputation for missing data). Secondary outcomes measured at 1, 3, 6 and 12 months post-quit date included: self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes per day, time to (re)lapse, adverse events, treatment adherence/compliance and acceptability, nicotine withdrawal/urge to smoke and health-care utilization/health-related quality of life.

Findings: Verified continuous abstinence rates at 6 months post-quit date were 12.1% (41 of 337) for cytisine versus 7.9% (27 of 342) for varenicline [risk difference 4.29%, 95% confidence interval (CI) = -0.22 to 8.79; relative risk 1.55; 95% CI = 0.97-2.46]. Sensitivity analyses confirmed that the findings were robust. Self-reported adverse events over 6 months occurred significantly more frequently in the varenicline group (cytisine: 313 events in 111 participants; varenicline: 509 events in 138 participants, incidence rate ratio 0.56, 95% CI = 0.49-0.65, P < 0.001) compared with the cytisine group. Common adverse events were headache, nausea and difficulty sleeping.

Conclusion: A randomized controlled trial found that cytisine was at least as effective as varenicline at supporting smoking abstinence in New Zealand indigenous Māori or whānau (extended-family) of Māori, with significantly fewer adverse events.

Trial registration: ClinicalTrials.gov NCT02957786.

Keywords: Cytisine; indigenous; non-inferiority; smoking; trial; varenicline.

Figure 1

Trial trofile: *not eligible for varenicline under special authority (n = 13), high risk/history of epilepsy (n = 5), outside study region (n = 5), not Māori or whānau of Māori (n = 5), currently using smoking cessation medication (n = 3), non‐daily smoker (n = 3), breastfeeding (n = 2), other trial participant in household (n = 2), severe renal disease (n = 1), contraindication to varenicline (n = 1), did not want to use varenicline (n = 1). **Did not want to use varenicline (n = 22), not eligible for varenicline under special authority (n = 11), high risk/history of epilepsy (n = 4), outside study region (n = 3), contraindication to varenicline (n = 3), unstable hyperthyroidism (n = 3), currently using smoking cessation medication (n = 1), breastfeeding (n = 1), no national health index number, which was required for the prescription (n = 1). ^aMissing: the number of participants who were contacted but did not provide data (this includes a subset where data had not been handled in accordance with the protocol, which were therefore counted as missing). ^bLost to follow‐up: the number of participants who could not be contacted at this follow‐up time‐point. ^cWithdrawn: the number of participants who withdrew from the trial (no further data were available)