The certainty of evidence is downgraded by imprecise results (few patients).
A systematic review and meta-analysis «Chang PH, Chiang CH, Ho WC et al. Combination therapy of varenicline with nicotine replacement therapy is better than varenicline alone: a systematic review and meta-analysis of randomized controlled »1 included 3 RCTs with 904 participants. Combination therapy of varenicline with nicotine replacement therapy (NRT) was better than varenicline alone at 3 months (OR 1.50, 95 % CI 1.14 to 1.97) and at 6 months (OR = 1.62, 95 % CI 1.18 to 2.23). However, this significance diminished after eliminating a study with pre-cessation treatment using nicotine patch.
In another systematic review and network meta-analysis «Thomas KH, Dalili MN, López-López JA et al. Smoking cessation medicines and e-cigarettes: a systematic review, network meta-analysis and cost-effectiveness analysis. Health Technol Assess 2021;25(59):»2 varenicline (standard dose) plus nicotine replacement therapy (standard dose) was ranked first for sustained abstinence (OR 5.75, 95% credible interval 2.27 to 14.90). Higher proportion of smokers who received counselling achieved sustained abstinence than those who did not receive counselling, and higher odds of sustained abstinence among participants with higher average dependence scores. The odds ratios for sustained abstinence were NRT standard 2.01 (1.68 to 2.41), NRT high 2.32 (1.88 to 2.86), bupropion standard 1.73 (1.43 to 2.10), varenicline standard 2.83 (2.34 to 3.39), bupropion standard plus NRT high 1.99 (0.70 to 5.47), varenicline standard plus bupropion standard 3.25 (1.35 to 7.92).