Cytisine for Smoking Cessation

Published

Walker N, et al. "Cytisine versus nicotine for smoking cessation". The New England Journal of Medicine. 2014. 371(25):2353-2362.
PubMed • Full text • PDF

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. Its low cost makes it an attractive option for smoking cessation. No large RCT had been performed to compare its efficacy to NRT.

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. However, whether it would receive FDA authorization and remain an inexpensive option is unknown.

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
• 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