Combining smoking cessation therapies improves abstinence rates

Varenicline in combination with nicotine replacement therapy was more effective than varenicline alone in helping smokers quit, a study found.

Researchers conducted a randomized, blinded, placebo-controlled clinical trial with a 12-week treatment period and 12 weeks of follow-up in 7 centers in South Africa from April 2011 to October 2012. Researchers randomized 446 generally healthy smokers in a 1:1 ratio. Eligible people were adults who sought assistance with smoking cessation, had smoked at least 10 cigarettes a day in the previous year and the month prior to screening, and had had no period of smoking abstinence longer than 3 months in the past year. Nicotine or placebo patch treatment began 2 weeks before the target quit date and continued for 12 weeks. Varenicline was started 1 week before the target quit date, continued for 12 weeks, and tapered off during week 13.

Tobacco abstinence was established and confirmed by exhaled carbon monoxide measurements at the target quit date and at intervals for up to 24 weeks. The primary end point was confirmed continuous abstinence for weeks 9 to 12 of the treatment. Secondary end points included point prevalence abstinence at 6 months, continuous abstinence rate from weeks 9 through 24, and adverse events.

Results appeared July 9 in the Journal of the American Medical Association.

Participants who received varenicline and active nicotine replacement therapy were more likely to achieve continuous abstinence at 12 weeks (55.4% vs 40.9%; P=0.007) and 24 weeks (49.0% vs 32.6%; P=0.004) and point prevalence abstinence at 24 weeks (65.1% vs 46.7%; P=0.002) than those receiving varenicline and placebo. The numbers needed to treat (NNT) to achieve 1 additional successful attempt at smoking cessation were 7 (95% CI, 5 to 20) for nicotine replacement therapy and 7 (95% CI, 4 to 14) for varenicline alone.

The mean weight gain in those who completed 6 months of follow-up was 3.0 kg (95% CI, 2.3 to 3.8 kg) in the patch group and 2.2 kg (95% CI, 1.7 to 2.8 kg) in the placebo group (P=0.09). The combination treatment group reported more nausea, sleep disturbances, skin reactions, constipation, and depression, but only skin reactions were significantly higher (14.4% vs. 7.8%; P=0.03), including localized erythema (n=21), itch (n=6), mild generalized reactions (n=3) and worsening of preexisting acne (n=1). The placebo patch group also had localized erythema (n=11) or itch (n=2), mild generalized dermatitis (n=3), and gingivitis (n=1) and reported more abnormal dreams and headaches.

Overall, 140 (78.2%) and 137 (76.5%) participants who were randomized to receive the nicotine replacement therapy patch and who completed the treatment period (12 weeks) showed at least an 80% adherence with varenicline and the patch, respectively, compared with 139 (80.3%) and 143 (82.7%) participants randomized to receive the placebo patch.

“The additive efficacy of combining the 2 drugs is not easily explained, given that both target α₄β2 nicotine receptors,” the authors wrote. “It is possible that neither varenicline nor nicotine fully saturate all α₄β2 nicotine receptors in the brain, leaving room for the action of the other. Alternatively, nicotine replacement may bind to different (additional) receptors involved in nicotine dependency.”

ACP Internist covered ways to help smokers quit in its Internal Medicine 2014 coverage.

In other news about smoking, e-cigarettes should be restricted or banned, or at as least closely regulated as medicines or tobacco products, until more information about their safety is available, major pulmonology subspecialty societies said in a joint position paper published July 9 in the American Journal of Respiratory and Critical Care Medicine.

In addition, a July 10 health policy brief from Health Affairs and the Robert Wood Johnson Foundation described federal policymakers' recent efforts to propose rules for e-cigarettes. The brief examined the background of federal policies, critics and supporters' views of e-cigarettes, the question of e-cigarettes' safety, whether or not they should be regulated by the FDA as a tobacco product or a medical device, and an FDA-proposed rule on regulating e-cigarettes.

ACP Internist covered the e-cigarette debate in its March 2014 issue.