Cytisine for Smoking Cessation
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Clinical Question
Among patients with tobacco abuse, is cytisine therapy noninferior to nicotine replacement therapy for abstinence at 1 month?
Bottom Line
Among patients with tobacco abuse, cytisine is superior to nicotine replacement therapy for abstinence at 1 month.
Major Points
Common therapies for smoking cessation include nicotine replacement therapy (NRT) and the partial nicotinic ACh agonist varenicline (brand name Champix/Chantix). Cytisine is a generic plant-derived alkaloid that has a similar target to varenicline that is an over-the-counter smoking cessation aide used in Eastern Europe.
This pragmatic trial by Walker and colleagues published in 2014 randomized 1,310 smokers who called a smoking quit phone line in New Zealand to cytisine or NRT. Both groups had low-intensity cessation support. Cytisine outperformed NRT for quit rate at 1 month and was found to be superior in this non-inferiority trial (40% vs. 31%; P<0.001; NNT 11). This difference was sustained at 6 months (22% vs. 15%; P=0.002; NNT 14). Cytisine was associated with a higher adverse event rate (most commonly nausea/vomiting and sleep disorders) than NRT (31% vs. 20%).
Given the promising results of this trial, there has been a call to bring cytisine to the US and Western Europe.
Guidelines
As of April 2015, no guidelines have been published that reflect the results of this trial.
Design
- Open label, randomized, pragmatic, non-inferiority trial
- N=1,310 (3,001 screened)
- Cytisine (n=655)
- Nicotine Replacement Therapy (NRT) (n=655)
- Setting: New Zealand
- Enrollment: 2011-2013
- Follow-up: Primary outcome at 1 month
- Analysis: Intention to treat
- Primary outcome: Abstinence at 1 month
Population
Inclusion Criteria
- Age ≥18 years
- Daily smoker
- Interested in quitting
- Caller of the New Zealand Quitline
Exclusion Criteria
- Pregnant or breastfeeding women
- Taking a medication for smoking cessation
- Enrollment in a different smoking cessation trial or program
- Pheochromocytoma
- BP >150/100
- Schizophrenia
- CV event in prior 2 weeks
Baseline Characteristics
From the Cytisine group. Groups were similar.
- Demographics: Female 57%, age 39 years, <12 years of education 53%
- Ethnicity: New Zealand Maori 33%, other 67%
- Cigarettes/day: 19
- Fagerstrom cigarette dependence score: 5.4 (out of 10, >5 is high dependence)
Interventions
- Callers to the Quitline were randomized in a 1:1 ratio in open-label fashion to a group with stratification by cigarette dependence, ethnicity, and sex to a group:
- Cytisine - Receipt of 25 days of medication by mail and NRT vouchers for patches, gums, or lozenges
- Participants were encouraged to quit smoking by day #5
- The medication was given:
- Day 1-3 - 1 tablet PO q2h while awake (up to of 6 tablets daily)
- Day 4-12 - 1 tablet PO q2.5h while awake (up to of 5 tablets daily)
- Day 13-16 - 1 tablet PO q3h while awake (up to of 4 tablets daily)
- Day 17-20 - 1 tablet PO q4-5h while awake (up to 3 tablets daily)
- Day 21-25 - 1 tablet PO q6h while awak (up to 2 tablets daily)
- NRT use was encouraged if they needed additional support by beyond day 25 or if they had not stopped smoking by day 25
- NRT - Receipt of vouchers for patches, gums, or lozenges
- Cytisine - Receipt of 25 days of medication by mail and NRT vouchers for patches, gums, or lozenges
- Both groups had low-intensity smoking cessation behavioral support by ways of a phonecall lasting for 10-15 minutes occurring an average of 3 times over 8 weeks
Outcomes
Presented as cytisine vs. NRT.
Primary Outcome
- Abstinence at 1 month
- By self-report.
- 40% vs. 31% (RR 1.3; 95% CI 1.1-1.5; P<0.001; NNT 11)
- This outcome remained significant on a sensitivity analysis including complete cases only and on a per-protocol analysis.
Secondary Outcomes
- Abstinence at other times
- 1 week: 60% vs. 46% (RR 1.3; 95% CI 1.2-1.4; P<0.001; NNT 7)
- 2 months: 31% vs. 22% (RR 1.4; 95% CI 1.2-1.7; P<0.001; NNT 11)
- 6 months: 22% vs. 15% (RR 1.4; 95% CI 1.1-1.8; P=0.002; NNT 14)
Additional Outcomes
- Use of NRT, cytisine group
- 4%
Adverse Events
- Any
- 31% vs. 20%
- Serious: 7% vs. 6%
- Deaths: 1 vs. 1 event
- Most frequent:
- Nausea/vomiting: 30 vs. 2 events
- Sleep disorder: 28 vs. 2 events
Criticisms
- Receipt of the study medication was direct for cytisine (by mail courier) and indirect for NRT (vouchers redeemable at pharmacies), which may have influenced adherence
- Open label design
- No laboratory confirmation of cessation
Funding
- Heath Research Council of New Zealand