An RCT with the combination of varenicline and bupropion for smoking cessation: clinical implications for front line use

Background and Aims Despite the availability of several efficacious smoking cessation treatments, fewer than 25% of smokers who quit remain abstinent 1year post-treatment. This study aimed to determine if varenicline and bupropion combination treatment would result in higher abstinence rates than varenicline alone. Design A double-blind, randomized, parallel-group smoking cessation clinical trial in which participants were exposed to 12weeks of treatment and followed for 12months. Setting Hospital-based out-patient clinic in Texas, USA specializing in cancer prevention. Participants A total of 385 community smokers (58.44% male) who smoked 1 pack of cigarettes/day [mean=19.66 cigarettes/day, standard deviation (SD)=9.45]; had average carbon monoxide (CO) of 26.43parts per million (SD=13.74); and were moderately dependent (Fagerstrom Test for Cigarette Dependence =4.79; SD=2.07). Interventions and comparator Smokers were randomized in a 3:1 (active: Placebo) ratio to 12weeks of treatment as follows: placebo (n=56), varenicline (Var; n=166), and varenicline + bupropion (Combo; n=163). Measurements A priori primary outcome: prolonged abstinence at 12months. Secondary outcomes: 7-day point prevalence abstinence and continuous abstinence; all abstinence measures at end of treatment and 6-month follow-ups. Findings Intention-to-treat analysis: the Combo group (n=163) failed to demonstrate superiority to the Var group (n=166) for prolonged abstinence at 12months [odds ratio (OR)=0.91, 95% confidence interval (CI)=0.50-1.64], supported by Bayes factor=0.06. Both the Var (OR=6.66, 95% CI=1.61-59.27) and Combo groups (OR=6.06, 95% CI=1.45-54.09) demonstrated superiority to the Placebo group (n=56; score=8.38, P<0.016). Conclusions The addition of bupropion to varenicline treatment does not appear to increase smoking abstinence rates above that of varenicline alone. The findings support previous research showing a consistently favorable effect of both varenicline and the combination of varenicline and bupropion on smoking cessation compared with placebo.