Adding nicotine replacement therapy to varenicline monotherapy didn't increase smoking cessation

In a randomized trial of 1,251 adults who smoked five or more cigarettes per day, neither varenicline plus a nicotine patch nor extended-duration treatment was superior to 12 weeks of varenicline monotherapy for abstinence.

Compared to 12 weeks of smoking cessation treatment with varenicline, neither 24 weeks of the medication nor combining it with nicotine patch therapy improved abstinence outcomes, a double-blind randomized trial found.

A total of 1,251 adults (mean age, 49.1 years; 54.0% women) who smoked five or more cigarettes per day participated in the trial, which was conducted at one research clinic in Madison, Wis., from Nov. 11, 2017, to July 9, 2020. Participants received six 15-minute cessation counseling sessions and were randomly assigned to one of four medication groups: varenicline monotherapy for 12 weeks (n=315), varenicline plus nicotine patch for 12 weeks (n=314), varenicline monotherapy for 24 weeks (n=311), or varenicline plus nicotine patch for 24 weeks (n=311). The primary outcome was self-reported seven-day point prevalence abstinence, which was biochemically confirmed by an exhaled carbon monoxide level of 5 ppm or less, at 52 weeks after the target quit day. Results were published online Oct. 19 by JAMA.

Overall, 751 participants (60.0%) completed treatment and 881 (70.4%) provided final follow-up data. For the primary outcome, no significant interaction was seen between medication type and medication duration (odds ratio [OR], 1.03 [95% CI, 0.91 to 1.17]; P=0.66). For patients randomized to 24- versus 12-week treatment duration, the primary outcome was achieved in 24.8% versus 24.3% (risk difference, −0.4% [95% CI, −5.2% to 4.3%]; OR, 1.01 [95% CI, 0.89 to 1.15]). For those randomized to varenicline combination therapy versus varenicline alone, the primary outcome was achieved in 24.3% versus 24.8% (risk difference, 0.4% [95% CI, −4.3% to 5.2%]; OR, 0.99 [95% CI, 0.87 to 1.12]). Across all groups, 24.0% to 30.9% developed nausea and 24.4% to 30.5% developed insomnia.

Among other limitations, COVID-19 restrictions prevented biochemical confirmation of abstinence in some participants, the study authors noted. They added that adherence to medication declined over the course of the study, that 23% of participants were lost to follow-up at one year, and that 9% withdrew from the study.

The results are consistent with two previously published studies that also did not find significant differences in smoking cessation between the combination of varenicline plus nicotine replacement therapy versus varenicline alone, an accompanying editorial noted. However, another study did find significantly higher continuous abstinence rates with the combination versus varenicline and a placebo patch, the editorialists noted.

“While waiting for future studies to provide more definitive answers, it is important for clinicians to recognize that most cigarette smokers pass through repeated cycles of short-term abstinence followed by relapse before achieving long-term abstinence,” they wrote. “Therefore, clinicians need to use a chronic disease management approach, which involves monitoring tobacco use over time and making frequent efforts to encourage and assist cigarette smokers in quitting tobacco products.”