Best smoking cessation strategy after failure of varenicline or combined nicotine replacement therapy

Most people who smoke do not successfully quit on their first attempt. Multiple quit attempts are usually required to achieve long-term success, but little evidence is available to guide treatment strategies after initial failure.To examine this issue, researchers at a tobacco treatment clinic in Houston, Texas determined the best subsequent strategy for patients who failed to quit smoking after an initial six weeks of treatment with varenicline or combined nicotine replacement therapy.The investigators conducted a double-blind, placebo-controlled, sequential multiple assignment randomized trial. The 490 volunteers were randomized to receive six weeks of varenicline or combined nicotine replacement therapy (nicotine patch + lozenge). After six weeks, nonabstainers were re-randomized to continue, switch or increase medication dosage for six additional weeks. Patients initially received varenicline 2 mg/day or combined nicotine replacement therapy with a 21 mg patch plus 2 mg lozenges (taken as needed, with recommended use of at least 6 lozenges/day). The re-randomized participants either continued with their initial therapies and dosages, switched between varenicline and combined nicotine replacement therapy, or increased dosages to varenicline 3 mg or two 21 mg nicotine patches (42 mg) plus 2 mg lozenges as needed. All patients received weekly brief (15-minute) behavioural counselling.The main outcome was biochemically verified seven-day abstinence at the end of 12 weeks of treatment.Results showed the following:The 490 randomized participants (43% female, mean age, 48.1 years) smoked an average of 20 cigarettes per day. After the first phase (6 weeks), 54 participants in the combined nicotine replacement therapy group were abstinent and continued their therapy. Of the 191 who were not abstinent, 151 were re-randomized. The 40 who did not return for re-randomization were assigned to continue their initial combined nicotine replacement therapy in phase 2 (to the end of treatment week 12). The end-of-treatment (12 weeks) abstinence rate for the 191 phase 1 nonabstainers was 8% (95% credible interval [CrI], 6%–10%) for the 90 (47%) who continued at the original dosage. It was 14% (CrI, 10%–18%) for the 50 (33%) who increased their combined nicotine replacement therapy dosage, and 14% (95%CrI, 10%–18%) for the 51 (34%) who switched to varenicline (absolute risk difference [RD], 6%; 95%CrI, 6%–11%), with more than 99% probability that either the dosage increase or switching strategy conferred benefit over continuing the initial dosage.After the first phase, 88 participants in the varenicline group were abstinent and continued their therapy. Of the 157 who were not abstinent, 122 were re-randomized and the 35 who did not return for re-randomization were assigned to continue with the original varenicline dosage. The end-of-treatment (12 weeks) abstinence rate for the 157 phase 1 nonabstainers was 20% (95%CrI, 16%–26%) for the 39 (32%) who increased their varenicline dosage, 0 (95%CrI, 0–0) for the 41 (34%) who switched to combined nicotine replacement therapy, and 3% (95%CrI, 1%–4%) for the 77 (49%) who were assigned to continue with the original varenicline dosage (absolute RD, −3%; 95%CrI, −4% to −1%), with more than 99% probability that continuing varenicline at the initial dosage was worse than switching to a higher dosage. Increasing the varenicline dosage had an absolute RD of 18% (95%CrI, 13%–24%) and a more than 99% probability of conferring benefit. Compared to continuing with the same medication dosage, no increased risk of adverse events was seen with the dosage increase for either medication.The authors concluded that for individuals who smoked but did not achieve abstinence after an initial six weeks of treatment with varenicline, increasing the dosage enhanced abstinence compared to continuing with the original dosage. For nonabstainers who were initially treated with combined nicotine replacement therapy, a dosage increase or a switch to varenicline enhanced abstinence. Both options may be viable rescue strategies for patients who fail to quit after an initial six weeks of varenicline or combined nicotine replacement therapy.Reference1. Cinciripini PM, Green CE, Shete S, et al. Smoking cessation after initial treatment failure with varenicline or nicotine replacement. A randomized clinical trial. JAMA 2024. Published online May 2, 2024. (accessed May 9, 2024).

Best smoking cessation strategy after failure of varenicline or combined nicotine replacement therapy

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