Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials

Abstract

Background: Many placebo-controlled trials have demonstrated the efficacy of individual pharmacotherapies approved for smoking cessation. However, few direct or indirect comparisons of such interventions have been conducted. We performed a meta-analysis to compare the treatment effects of 7 approved pharmacologic interventions for smoking cessation.

Methods: We searched the US Centers for Disease Control and Prevention's Tobacco Information and Prevention database as well as MEDLINE, EMBASE and the Cochrane Library for published reports of placebo-controlled, double-blind randomized controlled trials of pharmacotherapies for smoking cessation. We included studies that reported biochemically validated measures of abstinence at 6 and 12 months. We used a hierarchical Bayesian random-effects model to summarize the results for each intervention.

Results: We identified 70 published reports of 69 trials involving a total of 32 908 patients. Six of the 7 pharmacotherapies studied were found to be more efficacious than placebo: varenicline (odds ratio [OR] 2.41, 95% credible interval [CrI] 1.91-3.12), nicotine nasal spray (OR 2.37, 95% CrI 1.12-5.13), bupropion (OR 2.07, 95% CrI 1.73-2.55), transdermal nicotine (OR 2.07, 95% CrI 1.69-2.62), nicotine tablet (OR 2.06, 95% CrI 1.12-5.13) and nicotine gum (OR 1.71, 95% CrI 1.35-2.21). Similar results were obtained regardless of which measure of abstinence was used. Although the point estimate favoured nicotine inhaler over placebo (OR 2.17), these results were not conclusive because the credible interval included unity (95% CrI 0.95-5.43). When all 7 interventions were included in the same model, all were more efficacious than placebo. In our analysis of data from the varenicline trials that included bupropion control arms, we found that varenicline was superior to bupropion (OR 2.18, 95% CrI 1.09-4.08).

Interpretation: Varenicline, bupropion and the 5 nicotine replacement therapies were all more efficacious than placebo at promoting smoking abstinence at 6 and 12 months.

Figure 1: Retrieval and selection of randomized controlled trials of pharmacotherapies for smoking cessation.

Figure 2: Effect of bupropion on smoking cessation. Smoking cessation is defined by the most rigorous criterion of abstinence (the most conservative outcome reported in any given trial), based on the following ranking: continuous abstinence at 12 months; continuous abstinence at 6 months; point prevalence of abstinence at 12 months; point prevalence of abstinence at 6 months. The data have been adjusted for length of treatment and dosage. Trials are ordered according to the number of patients analyzed using the most rigorous criteria. The total number of patients represents the number of unique patients and thus is less than the sum of the individual studies. Details of the individual trials are summarized in Appendix 1 (available at www.cmaj.ca/cgi/content/full/179/2/135/DC2). CrI = credible interval.

Figure 3: Effect of nicotine gum on smoking cessation. Smoking cessation is defined by the most rigorous criterion of abstinence (see Figure 2 caption for definition and ranking). The data have been adjusted for dosage. Trials are ordered according to the number of patients analyzed using the most rigorous criteria. The total number of patients represents the number of unique patients and thus is less than the sum of the individual studies. Details of the individual trials are summarized in Appendix 2 (available at www.cmaj.ca/cgi/content/full/179/2/135/DC2). CrI = credible interval.

Figure 4: Effect of transdermal nicotine on smoking cessation. Smoking cessation is defined by the most rigorous criterion of abstinence (see Figure 2 caption for definition and ranking). Trials are ordered according to the number of patients analyzed using the most rigorous criteria. The total number of patients represents the number of unique patients and thus is less than the sum of the individual studies. Details of the individual trials are summarized in Appendix 3 (available at www.cmaj.ca/cgi/content/full/179/2/135/DC2). CrI = credible interval, ICRF GPRG = Imperial Cancer Research Fund General Practice Research Group, TNSG = Transdermal Nicotine Study Group.

Figure 5: Effect of varenicline on smoking cessation. Smoking cessation is defined by the most rigorous criterion of abstinence (see Figure 2 caption for definition and ranking). Trials are ordered according to the number of patients analyzed using the most rigorous criteria. The total number of patients represents the number of unique patients and thus is less than the sum of the individual studies. Details of the individual trials are summarized in Appendix 4 (available at www.cmaj.ca/cgi/content/full/179/2/135/DC2). CrI = credible interval.

Figure 6: Summary estimates of the effect of pharmacotherapies for smoking cessation on the odds of smoking cessation. Smoking cessation is defined by the most rigorous criterion of abstinence (see Figure 2 caption for definition and ranking). Data have been adjusted for mean age, sex and mean number of cigarettes per day. CrI = credible interval.

Figure 7: Direct comparison of the effect of varenicline and bupropion on smoking cessation, based on results from varenicline trials that had a bupropion control arm. Smoking cessation is defined by the most rigorous criterion of abstinence (see Figure 2 caption for definition and ranking). Trials are ordered based on the number of patients analyzed using the most rigorous criteria. CrI = credible interval.