A 24-week course of varenicline improved quit rates among smokers who were unwilling or unable to stop smoking abruptly but preferred to gradually reduce their use of cigarettes, according to a report published online Feb. 17 in JAMA.
In an industry-sponsored, randomized, double-blind, controlled trial, participants who were given varenicline showed higher quit rates at the end of treatment as well as 1 year later, compared with those given placebo, said Dr. Jon O. Ebbert of the Mayo Clinic, Rochester, Minn., and his associates.
Current U.S. clinical practice guidelines recommend that smokers set an immediate quit date and quit abruptly, “even though only 8% of smokers report being ready to quit within the next month.” The findings of this study show that a more gradual, reduce-to-quit approach also can be effective, and “would be expected to be of interest to 14 million of the 42 million current smokers in this country,” the investigators noted.
The study was performed at 61 medical centers in 10 countries during a 2-year period. The 1,510 participants would not quit abruptly, as is recommended, but were willing to reduce their smoking and make a quit attempt within the next 3 months. They were asked to reduce their smoking rate by 50% or more by week 4, to further reduce it by 75% or more by week 8, and to quit altogether by week 12.
Study participants, who smoked an average of 10 or more cigarettes per day at baseline, were randomly assigned to receive varenicline (760 patients) or a matching placebo (750 patients) for 24 weeks. All also received written materials and smoking cessation counseling focused on reduction techniques, problem-solving, and skills training. This was provided during 18 clinic visits and 10 telephone sessions of about 10 minutes’ duration.
The primary efficacy endpoint was the continuous abstinence rate during weeks 15-24, which was self-reported by the participants and confirmed using exhaled carbon monoxide measurements. This rate was significantly higher for the varenicline group (32.1%) than for the placebo group (6.9%). The continuous abstinence rate remained significantly higher through 1 year of follow-up for varenicline (27%) than for placebo (9.9%).
In addition, the median time to abstinence was significantly shorter with varenicline (50 days) than with placebo (85 days). Results of sensitivity analyses confirmed those of the primary analysis, the investigators said ( JAMA 2015 Feb. 17;313:687-94 ).
The percentage of participants who reported adverse events was higher with varenicline (82.3% vs. 72.5%), and the difference was largely accounted for by increases in nausea, abnormal dreams, insomnia, constipation, vomiting, and weight gain. Rates of serious adverse events were similar between the two study groups, as were rates of treatment discontinuation (8.4% for varenicline and 7% for placebo). In particular, rates of suicidal ideation or behavior and depression scores were not significantly higher with varenicline.
The study findings indicate that prescribing varenicline “with a recommendation to reduce the number of cigarettes smoked per day, with the eventual goal of quitting, could be a useful therapeutic option for this population of smokers,” Dr. Ebbert and his associates said.
One limitation of this study was that patients were excluded from participating if they had severe psychiatric, pulmonary, cardiovascular, or cerebrovascular disease, which hinders the generalizability of the results to a broader population of smokers. In addition, study participants received significant counseling support that would not necessarily be available to patients in real-world clinical practice, so quit rates would be expected to be lower in actual practice, they added.
This study was funded by Pfizer, maker of varenicline (Chantix). Pfizer also participated in the design and conduct of the study; the collection, analysis, and interpretation of the data; and manuscript preparation. Dr. Ebbert reported receiving grants from Pfizer, JHP Pharmaceuticals, and Orexigen, as well as personal fees from GlaxoSmithKline. His associates reported numerous ties to industry sources.
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