A Cochrane review «Nicotine receptor partial agonists for smoking cessation»1 «Livingstone-Banks J, Fanshawe TR, Thomas KH, et al. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2023;5(5):CD006103 »1 included 68 trials involving over 37 000 participants testing varenicline. Varenicline was more effective than placebo for abstinence at six months or longer (RR 2.32, 95% CI 2.15 to 2.51; 41 studies, n=17 395). The RR for varenicline vs bupropion was 1.36 (95% CI 1.25 to 1.49; 9 studies, n=7 560), for varenicline vs nicotine replacement therapy (NRT) monotherapy RR was 1.25 (95% CI 1.14 to 1.37; 11 studies, n=7 572), and for varenicline vs. combination NRT 1.02 (95% CI 0.87 to 1.20; 5 studies, n=2 344). People taking varenicline were more likely to report serious adverse events (SAEs) than those not taking it (RR 1.23, 95% CI 1.01 to 1.48; 26 studies, n=14 356). Absolute rates for serious adverse events were 3.3% and 2.7% in varenicline and control arms respectively. While point estimates suggested increased risk of cardiac SAEs (RR 1.20, 95% CI 0.79 to 1.84; 18 studies, n=7 151), and decreased risk of neuropsychiatric SAEs (RR 0.89, 95% CI 0.61 to 1.29; 22 studies, n=7 846), in both cases evidence was limited by imprecision, and confidence intervals were compatible with both benefit and harm.
Another Cochrane review «Pharmacological and electronic cigarette interventions for smoking cessation in adults: component network meta‐analyses»2 «Lindson N, Theodoulou A, Ordóñez-Mena JM, ym. Pharmacological and electronic cigarette interventions for smoking cessation in adults: component network meta-analyses. Cochrane Database Syst Rev 2023;9»4 included a component network meta-analysis with 319 RCTs and 157 179 participants. Varenicline (OR 2.33, 95% CrI 2.02 to 2.68; 67 RCTs, n=16 430) and cytisine (OR 2.21, 95% CrI 1.66 to 2.97; 7 RCTs, n=3 848) were associated with higher quit rates than control. Combination NRT (patch and a fast-acting form of NRT (OR 1.93, 95% CrI 1.61 to 2.34), nicotine patch alone (OR 1.37, 95% CrI 1.20 to 1.56; 105 RCTs, 37 319), fast-acting NRT alone (OR 1.41, 95% CrI 1.29 to 1.55; 120 RCTs, 31 756) and bupropion (OR 1.43, 95% CrI 1.26 to 1.62; 71 RCTs, n=14 759) were more effective than control.
Another Cochrane review «Pharmacological interventions for smoking cessation: an overview and network meta‐analysis»3 «Cahill K, Stevens S, Perera R et al. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev 2013;(5):CD009329. »2 included a network meta-analysis of 12 treatment-specific reviews (267 studies) involving 101 804 participants. Varenicline increased the odds of quitting compared with placebo (OR 2.88; 95% credible interval= CredI 2.40 to 3.47; direct comparisons, 15 trials). Varenicline was superior to single forms of NRT (OR 1.57; 95% CredI 1.29 to 1.91; indirect comparison), and to bupropion (OR 1.59; 95% CredI 1.29 to 1.96; indirect comparison). Varenicline was more effective than nicotine patch (OR 1.51; 95% CredI 1.22 to 1.87; indirect comparison), than nicotine gum (OR 1.72; 95% CredI 1.38 to 2.13; indirect comparison), and than 'other' NRT (inhaler, spray, tablets, lozenges; OR 1.42; 95% CredI 1.12 to 1.79), but was not more effective than combination NRT (OR 1.06; 95% CredI 0.75 to 1.48; indirect comparison).
The serious adverse events (SAEs) meta-analysis found no difference between the varenicline and placebo arms (RR 1.06; 95% CI 0.72 to 1.55 RR 1.06; 14 trials, n=6333 participants; event rates for any SAE were 2.1% in the varenicline arms and 2.0% in the placebo arms), and subgroup analyses detected no significant excess of neuropsychiatric events (RR 0.53; 95% CI 0.17 to 1.67), or of cardiac events (RR 1.26; 95% CI 0.62 to 2.56).
An RCT «Benowitz NL, Pipe A, West R et al. Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers: A Randomized Clinical Trial. JAMA Intern Med 2018;178(5):622-631. »3 assessing the cardiovascular safety risk of smoking cessation treatments included 8058 participants randomized to varenicline, 1 mg twice daily; bupropion hydrochloride, 150 mg twice daily; or nicotine replacement therapy, 21-mg/d patch with tapering. The incidence of cardiovascular events during treatment and follow-up was low (<0.5% for major adverse cardiovascular event: cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and did not differ significantly by treatment.