For tobacco-dependent adults in whom treatment is being initiated, we recommend varenicline over a nicotine patch (strong recommendation, moderate certainty in the estimated effects).^47-49)

Benefits: Compared with a nicotine patch, varenicline increased long-term abstinence, measured as 7-day point prevalence abstinence at 6-month follow-up (RR, 1.20; 95% CI, 1.09–1.32)

Harms and burdens: Varenicline likely reduced the risk of SAEs compared with a nicotine patch (RR, 0.72; 95% CI, 0.52–1.00)

Varenicline may also reduce relapse at the end of follow-up compared with a nicotine patch (HR, 0.93; 95% CI, 0.78–1.11)

For tobacco-dependent adults in whom treatment is being initiated, we recommend varenicline over bupropion (strong recommendation, moderate certainty in the estimated effects).¹⁸⁾

Benefits: Varenicline increased the 7-day point-prevalence of tobacco abstinence at 6-month follow-up compared with bupropion (RR, 1.30; 95% CI, 1.19–1.42)

Harms and burdens: Varenicline treatment probably reduced the risk of SAEs compared with bupropion (RR, 0.81; 95% CI, 0.57–1.16)

For tobacco-dependent adults in whom treatment is being initiated, we suggest varenicline plus a nicotine patch over varenicline alone (conditional recommendation, low certainty in the estimated effects).

Benefits: Varenicline plus a nicotine patch significantly increased abstinence compared with varenicline alone, measured as 7-day point-prevalence abstinence at 6 months or later, when assessed by self report and confirmed by eCO (RR, 1.36; 95% CI, 1.07–1.72)^43,44)

Harms and burdens: Varenicline plus a nicotine patch may increase the risk of SAEs slightly compared with varenicline alone (RR, 1.06; 95% CI, 0.27–4.05)^42-45)

For tobacco-dependent adults in whom treatment is being initiated, we suggest varenicline over electronic cigarettes (conditional recommendation, very low certainty in the estimated effects).

Benefits: varenicline might lead to an increase in point-prevalence abstinence during treatment at 3 months when compared with electronic cigarettes, but the evidence is very uncertain (RR, 1.10; 95% CI, 0.73%–1.60%)¹⁸⁾

Harms and burdens: The indirect evidence showed that varenicline might decrease the RR of SAEs compared with electronic cigarettes, but the evidence is very uncertain (RR, 0.32; 95% CI, 0.071–0.82)^43,44)

In tobacco-dependent adults who are not ready to discontinue tobacco use, we recommend that clinicians begin treatment with varenicline rather than waiting until patients are ready to stop tobacco use (strong recommendation, moderate certainty in the estimated effects).

Benefits: More smokers were able to stop smoking when treated with varenicline, despite initial reluctance. Using 7-day point prevalence abstinence at 6 months after treatment, varenicline increased abstinence compared with waiting for affirmation of readiness (RR, 2.00; 95% CI, 1.70–2.35)

Harms and burdens: Varenicline likely increased SAEs associated with treatment (RR, 1.75; 95% CI, 0.98–3.13)

For tobacco-dependent adults for whom treatment is being initiated with a controller, we recommend using extended-duration (>12 wk) over standard-duration (6–12 wk) therapy (strong recommendation, moderate certainty in the estimated effects).

Benefits: Compared with standard duration controller therapy, extended duration therapy probably increased abstinence at 1-year follow-up, measured as 7-day point-prevalence abstinence, (RR, 1.22; 95% CI, 1.07–1.39), and reduced relapse assessed at 12 to 18 months after initiation of therapy (HR, 0.43; 95% CI, 0.29–0.64)

Harms and burdens: Compared with standard-duration controller therapy, extended-duration therapy probably increased SAEs slightly (RR, 1.37; 95% CI, 0.79–2.36)