Primary Care Corner with Geoffrey Modest: Smoking cessation with combo varenicline and nicotine patches
30 Sep, 14 | by EBM
I have posted a few blogs in the past year or so on the potential of the combination of varenicline plus nicotine patch. This is not an intuitive combo, since varenicline blocks with high affinity the nicotinic cholinergic receptor a4b2, presumably the principal mediator of nicotine dependence, both blocking nicotine effects but also with some agonist activity — though there may be other important receptors involved as well. JAMA published the largest study on the combo (see DOI:10.1001/jama.2014.7195). South African study of 435 smokers randomized to 12-week intervention of varenicline plus placebo patch vs. varenicline plus nicotine patch.
–Nicotine or placebo patch (15-mg nicotine patch, left on for 16h/day) begun 2 weeks before target quit date (TQD). Varenicline begun 1 week before. All continued until week 12 after TQD. Varenicline begun with usual up-titration (as per the chantix starter packet), and similarly tapered down in the last week.
–Mean age of patients was 46.3, mean smoking 16 cigarettes/d, 26.5 years of smoking with therefore 21 pack-years smoking, 1.5 previous quit attempts. 62% completed the study
–Primary endpoint: the % of people able to maintain complete abstinence from smoking for the last 4 weeks of treatment. Secondary endpoint was point prevalence of abstinence at 6 months. Continuous rate of abstinence from weeks 9-24, and adverse events. Tobacco abstinence determined by carbon monoxide measurements at TQD and up to 24 weeks later
–Combo treatment associated with higher continuous abstinence rate at 12 weeks (55.4% vs 40.9%; OR 1.85 [1.19-2.89], p=0.007); and at 24 weeks (49.0% vs 32.6%; OR 1.98 [1.25-3.14], p=0.004); and point prevalence abstinence at 6 months (65.1% vs 46.7%; OR 2.13 [1.32-3.43], p=0.002). Interestingly, the combo therapy did not decrease nicotine craving more than varenicline alone.
–More nausea in combo group, as well as sleep disturbance, skin reactions (mostly from the patch), constipation, and depression; but only skin reactions reached statistical significance (14.4% vs 7.8%, p=0.03). The varenicline alone group had more abnormal dreams and headaches (non-significant). Overall mean weight gain was 3.0 kg in the combo group and 2.2 kg with varenicline alone.
So, very impressive abstinence rates with combo therapy. combo therapy overall is better than monotherapy (even combo of long-acting nicotine patches with short-acting nicotine gum/lozenges, as well as combo of patches with bupropion). It would be interesting to have head-to-head comparison of varenicline/patch vs. bupropion/patch vs. combo patch/gum to find the most advantageous combination. But this study, I think, is an important one, adding a potent combo therapy to help people decrease the most significant preventable cause of morbidity/mortality from cardiovasc and respiratory diseases.