No significant difference was seen in smoking cessation rates at 6-months and a year among smokers treated with nicotine patches alone, a combination nicotine patches and lozenges, or the anti-smoking drug varenicline (Chantix) in a head-to-head comparison of the three treatments.

In the first randomized, open-label trial to compare the pharmacotherapies varenicline and combination nicotine replacement therapy (C-NRT) in smokers motivated to quit, 12-weeks of treatment with the two therapies or nicotine patches alone resulted in 52-week point-prevalence abstinence rates ranging from 19% to 21%.

All three treatments were well tolerated, but smokers who took varenicline had a higher incidence of adverse events, including vivid dreams, insomnia, nausea, and constipation, researcher Timothy Baker, PhD, of the University Of Wisconsin School of Medicine and Public Health, Madison, and colleagues wrote in the Jan. 26 issue of JAMA.

Action Points Note that this randomized trial found that nicotine patches, nicotine patch + lozenge, and varenicline were all equally efficacious at achieving sustained quit rates in smokers.

Be aware that only 20% of patients in all three arms of the trial stayed quit at one year after randomization.

The findings appear to contradict a 2013 Cochrane meta-analysis, and several other meta-analyses, which all showed varenicline and C-NRT to be more effective than nicotine patches alone for helping smokers kick the habit.

The researchers concluded that the results "raise questions about the relative effectiveness of intense smoking pharmacotherapies."

"We were really surprised when we found that all three of these treatments were equally effective," Baker told MedPage Today in a telephone interview.

Compared with nicotine patches alone, varenicline or C-NRT users had significantly reduce withdrawal and craving symptoms during the early post-target quit date (TQD) period, and C-NRT use was associated with higher initial abstinence rates than the other two treatments.

"However, neither of these early post TQD effects translated into superior 26- and 52-week abstinence," the researchers wrote.

The study included 1,086 smokers randomized to one of three 12-week open-label smoking cessation treatments: nicotine patch alone (n=241), varenicline (n=424) or nicotine patch, and lozenge (n=421). Six counseling sessions were also offered to study participants.

The primary outcome was carbon monoxide-confirmed self-reported 7-day point-prevalence abstinence at 26 weeks. Secondary outcomes were carbon monoxide-confirmed self-reported initial abstinence, prolonged abstinence at 26-weeks, and point-prevalence abstinence at weeks, 4, 12, and 52.

The mean age of the study participants was 48 years, 67% were white, 52% were women, and they smoked an average of 17 cigarettes a day.

Among the main findings:

No significant differences were seen in point-prevalence abstinence at 26 weeks (nicotine patch, 22.8% [55/241]; varenicline, 23.6% [100/424]; and C-NRT, 26.8% [113/421]) or at 52 weeks (nicotine patch, 20.8% [50/241]; varenicline, 19.1% [81/424]; and C-NRT, 20.2% [85/421]).

Risk differences for abstinence were: for patch vs. varenicline, −0.76% (95% CI, −7.4%to 5.9%); for patch versus C-NRT, −4.0% (95% CI, −10.8% to 2.8%); and for varenicline versus C-NRT, −3.3% (95% CI, −9.1% to 2.6%).

Mean craving scores were significantly lower among the varenicline and C-NRT groups, compared to the patch mono-treatment group: C-NRT (mean difference 0.55; 95% CI 0.25-0.84) and varenicline (mean difference 0.58; 95% CI 0.29-0.87) in both adjusted and unadjusted models (P<0.05 for both).

The long-term efficacy of all three treatments was smaller than has been reported in many previous randomized trials, and the researchers suggested that this may be due to a lower cumulative level of tobacco dependence among the study cohort.

"In general, smokers are smoking fewer cigarettes per day now than they did in the past," they wrote. "Thus, relative to participants in other varenicline and C-NRT studies (from 2004-2009), the current sample not only reported smoking fewer cigarettes per day (by about 5-6 per day on average) but also scored lower on some dependence indexes."

Baker added that the study was not powered to determine if varenicline and C-NRT are more effective than nicotine patches alone for the treatment of very heavy smokers.

Even though varenicline users experienced more treatment side effects, Baker said the study findings should not be interpreted as favoring nicotine replacement therapies over varenicline.

"All three of these treatments are effective," he said. "We have 40 million smokers in America today and about 80% of them tell us they want to quit. The big tragedy is that most of them are leaving their doctor's offices with no treatment at all and without even discussing smoking cessation."