Does the nicotine metabolite ratio moderate smoking cessation treatment outcomes in real-world settings? A prospective study

Lion Shahab, Linda Bauld, Ann Mcneill, Rachel F. Tyndale

Research output: Contribution to journalArticlepeer-review


BACKGROUND AND AIMS: In smoking treatment trials comparing varenicline with transdermal nicotine replacement therapy (NRT), stratified by nicotine metabolite (3-hydroxycotinine/cotinine) ratio (NMR), the relative benefit of varenicline is greater among normal rather than slow metabolisers. This study tested if the relative effectiveness of varenicline and NRT is associated with NMR status in a natural treatment setting. A secondary aim was to test if this relationship is moderated by behavioural support.

DESIGN: Prospective observational multi-centre study with 4-week and 52-week follow-up.

SETTING: Nine English Stop Smoking Services (SSS) PARTICIPANTS: Data came from 1,556 smokers (aged ≥16 years) attending SSS between March-2012 and March-2013.

INTERVENTIONS: Participants received pharmacotherapy together with behavioural support.

MEASUREMENTS: The primary outcome was carbon-monoxide verified continuous abstinence at both follow-up times. Main explanatory variables were 1) NMR status (slow [NMR<0.31, N=454] vs. normal [NMR≥0.31, N=1,109] metabolisers); 2) Pharmacotherapy (varenicline vs. NRT) and 3) Behavioural support (individual vs. group-based treatment). Analyses adjusted for baseline sociodemographic, SSS, mental/physical health and smoking characteristics.

FINDINGS: Of participants, 44.2% (95% confidence interval (CI) 41.7-46.6%) and 8.0% (95%CI 6.8-9.5%) were continuously abstinent at 4-weeks and 52-weeks. Varenicline was more effective than NRT at 4-weeks (p<0.001) but only marginally so at 52-weeks (p=0.061). There was no or inclusive evidence that NMR status moderated relative efficacy of varenicline and NRT at 4-week (p=0.60, Bayes Factor (BF)=0.25) or 52-week follow-ups (p=0.74, BF=0.73). However, this relationship was moderated by behavioural support (p=0.012): the relative benefit of varenicline over NRT at 52-week follow-up was greater in slow, not normal, metabolisers receiving group rather than individual support (p=0.012).

CONCLUSIONS: In a real-world setting, the nicotine metabolite ratio status of treatment-seeking smokers does not appear to contribute substantially to the differential effectiveness of varenicline and nicotine replacement therapy in Stop Smoking Services, when both pharmacotherapy and behavioural support are self-selected.

Original languageEnglish
Pages (from-to)304-314
Issue number2
Early online date1 Oct 2018
Publication statusPublished - Feb 2019

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