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Nicotine receptor partial agonists for smoking cessation (Review)

Livingstone-Banks J et al (2023)

Cochrane Database of Systematic Reviews - 10.1002/14651858.CD006103.pub9.

Evidence Categories

  • Care setting: Community setting
  • Care setting: Primary care
  • Population group: Adults
  • Intervention: Varenicline
  • Intervention: Other Pharmacotherapies
  • Outcome: Smoking cessation
  • Outcome: Changes to smoking rates

Type of Evidence

Systematic Review

Aims

To assess the effectiveness of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation.

(Please Note: Varenicline (brand name Champix) is not currently available in the UK. It has been withdrawn as a precaution because of an impurity found in the medicine. It's not yet known whether it will be available again in future.)

Findings

75 trials of 45,049 people; 45 were new for this update.

The authors found moderate-certainty evidence (limited by heterogeneity) that cytisine helps more people to quit smoking than placebo (RR 1.30, 95% confidence interval (CI) 1.15 to 1.47; I2 = 83%; 4 studies, 4623 participants), and no evidence of a difference in the number reporting SAEs (RR 1.04, 95% CI 0.78 to 1.37; I2 = 0%; 3 studies, 3781 participants; low-certainty evidence). Serious Adverse Effects (SAE) evidence was limited by imprecision.

The authors found high-certainty evidence that varenicline helps more people to quit than placebo (RR 2.32, 95% CI 2.15 to 2.51; I2 = 60%, 41 studies, 17,395 participants), and moderate-certainty evidence that people taking varenicline are more likely to report SAEs than those not taking it (RR 1.23, 95% CI 1.01 to 1.48; I2 = 0%; 26 studies, 14,356 participants).

Pooled results from studies that randomised people to receive cytisine or varenicline found no clear evidence of difference in quit rates (RR 1.00, 95% CI 0.79 to 1.26; I2 = 65%; 2 studies, 2131 participants; low-certainty evidence) and reported SAEs (RR 0.67, 95% CI 0.44 to 1.03; I2 = 45%; 2 studies, 2017 participants; low-certainty evidence).

The authors found high-certainty evidence that varenicline helps more people to quit than bupropion (RR 1.36, 95% CI 1.25 to 1.49; I2 = 0%; 9 studies, 7560 participants), and no clear evidence of difference in rates of SAEs (RR 0.89, 95% CI 0.61 to 1.31; I2 = 0%; 5 studies, 5317 participants),

They found high-certainty evidence that varenicline helps more people to quit than a single form of nicotine replacement therapy (NRT) (RR 1.25, 95% CI 1.14 to 1.37; I2 = 28%; 11 studies, 7572 participants), and low-certainty evidence, limited by imprecision, of fewer reported SAEs (RR 0.70, 95% CI 0.50 to 0.99; I2 = 24%; 6 studies, 6535 participants).

The authors found no clear evidence of a difference in quit rates between varenicline and dual-form NRT (RR 1.02, 95% CI 0.87 to 1.20; I2 = 0%; 5 studies, 2344 participants; low-certainty evidence, downgraded because of imprecision).

Conclusions

Cytisine and varenicline both help more people to quit smoking than placebo or no medication. Varenicline is more effective at helping people to quit smoking than bupropion, or a single form of NRT, and may be as or more effective than dual-form NRT. People taking varenicline are probably more likely to experience SAEs than those not taking it, and while there may be increased risk of cardiac SAEs and decreased risk of neuropsychiatric SAEs, evidence was compatible with both benefit and harm. Cytisine may lead to fewer people reporting SAEs than varenicline. Based on studies that directly compared cytisine and varenicline, there may be no difference or a benefit from either medication for quitting smoking.

Future trials should test the effectiveness and safety of cytisine compared with varenicline and other pharmacotherapies, and should also test variations in dose and duration. There is limited benefit to be gained from more trials testing the effect of standard-dose varenicline compared with placebo for smoking cessation. Further trials on varenicline should test variations in dose and duration, and compare varenicline with e-cigarettes for smoking cessation.

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