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Evidence summaries

Varenicline for Smoking Cessation

Varenicline together with brief counselling is effective for smoking cessation compared with placebo. Varenicline is more effective than bupropion, and as effective as combination nicotine replacement therapy. Level of evidence: "A"

A Cochrane review [Abstract] 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 [Abstract] 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[Abstract] 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 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.

References

  • Livingstone-Banks J, Fanshawe TR, Thomas KH, et al. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2023;5(5):CD006103 [PubMed]
  • 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. [PubMed]
  • 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. [PubMed]
  • 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(9):CD015226 [PubMed]

Primary/Secondary Keywords