Effectiveness of smoking cessation therapies: a systematic review and meta-analysis

Background: Smoking remains the leading preventable cause of premature deaths. Several pharmacological interventions now exist to aid smokers in cessation. These include Nicotine Replacement Therapy [NRT], bupropion, and varenicline. We aimed to assess their relative efficacy in smoking cessation by conducting a systematic review and meta-analysis. Methods: We searched 10 electronic medical databases ( inception to Sept. 2006) and bibliographies of published reviews. We selected randomized controlled trials [RCTs] evaluating interventions for smoking cessation at 1 year, through chemical confirmation. Our primary endpoint was smoking cessation at 1 year. Secondary endpoints included short-term smoking cessation (similar to 3 months) and adverse events. We conducted random-effects meta-analysis and meta-regression. We compared treatment effects across interventions using head-to-head trials and when these did not exist, we calculated indirect comparisons. Results: We identified 70 trials of NRT versus control at 1 year, Odds Ratio [ OR] 1.71, 95% Confidence Interval [CI], 1.55 - 1.88, P =< 0.0001). This was consistent when examining all placebo-controlled trials ( 49 RCTs, OR 1.78, 95% CI, 1.60 - 1.99), NRT gum ( OR 1.60, 95% CI, 1.37 - 1.86) or patch ( OR 1.63, 95% CI, 1.41 - 1.89). NRT also reduced smoking at 3 months ( OR 1.98, 95% CI, 1.77 - 2.21). Bupropion trials were superior to controls at 1 year ( 12 RCTs, OR 1.56, 95% CI, 1.10 - 2.21, P = 0.01) and at 3 months ( OR 2.13, 95% CI, 1.72 - 2.64). Two RCTs evaluated the superiority of bupropion versus NRT at 1 year ( OR 1.14, 95% CI, 0.20 - 6.42). Varenicline was superior to placebo at 1 year ( 4 RCTs, OR 2.96, 95% CI, 2.12 - 4.12, P =< 0.0001) and also at approximately 3 months ( OR 3.75, 95% CI, 2.65 - 5.30). Three RCTs evaluated the effectiveness of varenicline versus bupropion at 1 year ( OR 1.58, 95% CI, 1.22 - 2.05) and at approximately 3 months ( OR 1.61, 95% CI, 1.16 - 2.21). Using indirect comparisons, varenicline was superior to NRT when compared to placebo controls ( OR 1.66, 95% CI 1.17 - 2.36, P = 0.004) or to all controls at 1 year ( OR 1.73, 95% CI 1.22 - 2.45, P = 0.001). This was also the case for 3-month data. Adverse events were not systematically different across studies. Conclusion: NRT, bupropion and varenicline all provide therapeutic effects in assisting with smoking cessation. Direct and indirect comparisons identify a hierarchy of effectiveness.