varenicline for almost-ready smoker cessation

JAMA presented a randomized controlled drug-company sponsored trial assessing the utility of varenicline for patients who are not quite ready to quit smoking (see smoking varenicline slowly cutting down JAMA 2015 in dropbox, or JAMA. 2015;313(7):687-694). details:

--760 patients from 61 centers in 10 countries were randomized to varenicline titrated to 1mg bid (vs 750 placed on placebo). all patients felt they were not ready to quit within the next month but were willing to reduce smoking and make a quit attempt within the next 3 months.
--mean age 45. 56% men, 62% white, 5% black, 23% asian. average 20 cigarettes/d. 20% never attempted to quit before, 25% tried once, 16% twice and 40% at least 3 times
--patients had a reduction target of 50% or more by 4 weeks, 75% or more by 8 weeks, then a quit attempt by 12 weeks
--primary endpoint: carbon monoxide-confirmed self-reported abstinence during weeks 15-24. secondary outcomes were carbon-monoxide-confirmed self-reported abstinence for weeks 21-24 and weeks 21-52.

--results:
    --varenicline group had higher abstinence rates during weeks 15-24 (32.1%, vs 6.9% with placebo), risk difference of 25.2% and relative risk of 4.6 (3.5-6.1)
    --varenicline group had higher abstinence rates during weeks 21-24 (37.8%, vs 12.5% with placebo), risk difference of 25.2% and relative risk of 3.0 (2.4-3.7)
    --varenicline group had higher abstinence rates during weeks 21-52 (27.0%, vs 9.9% with placebo), risk difference of 17.1% and relative risk of 2.7 (2.1-3.5).
    --the curves of varenicline vs placebo were flat from 28-52 weeks (ie, no evidence of deterioration with varenicline -- see graph below)
    ​--of those who were able to quit completely, those on varenicline quit a median of 50 days after starting the med; those on placebo quit after 85 days
    ​--serious adverse events in 3.7% on varenicline and 2.2% on placebo. significantly more adverse events with varenicline were: nausea (27.8%), abnormal dreams (11.5%), constipation (5.1%), weight increase (3.7%). the constipation and weight gain happen just with smoking cessation alone. no significant psych issues (those with baseline severe psych issues were excluded from the study).

perspective: it is clear that many current smokers want to quit (44% in a telephone survey reported in 2007), but only about 8% feel that they are ready to quit in the next month. Practice guidelines (eg the US Public Health Service​) typically suggest that smokers quit abruptly, and it is commonly felt that aids are not useful unless the patient is really ready to quit. so, i think this is a pretty powerful study, which serves to reframe the approach to smoking cessation a bit. lots of participants from many different countries. and in primary care, we all see many patients who want to cutback and quit soon but are unable to specify a quit date. the long term (1 year) abstinence rate of close to 30% is very impressive. this study is a further impetus to treat smokers and reach out to those who previously we might not have considered to be good candidates.

The graph below shows the 7-day point prevalence of smoking abstinence, without much of a falloff in efficacy after 28 weeks.


cid:473b509c-313e-4704-bd15-14ef80fdc41d

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