Summary of findings for the main comparison.
Nicotine receptor partial agonists for smoking cessation
| Varenicline versus placebo or other first‐line treatments for smoking cessation | ||||||
| Patient or population: Individuals who smoke tobacco Setting: Varied Intervention: Varenicline Comparison: Varied controls | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Risk with control | Corresponding risk with varenicline | |||||
| Varenicline vs placebo: continuous/sustained abstinence at longest follow‐up (24+ weeks) | Study population (where risk refers to quitters) | RR 2.24 (2.06 to 2.43) | 12,625 (27 RCTs) | ⊕⊕⊕⊕ HIGH 1, 2 | ||
| 111 per 1000 | 250 per 1000 (230 to 271) | |||||
| Varenicline vs bupropion: continuous/sustained abstinence (24 weeks) | Study population (where risk refers to quitters) | RR 1.39 (1.25 to 1.54) | 5877 (5 RCTs) |
⊕⊕⊕⊕ HIGH | ||
| 171 per 1000 | 238 per 1000 (214 to 264) | |||||
| Varenicline vs NRT: point prevalence abstinence (24 weeks) | Study population (where risk refers to quitters) | RR 1.25 (1.14 to 1.37) | 6264 (8 RCTs) | ⊕⊕⊕⊝ MODERATE 3 | ||
| 189 per 1000 | 237 per 1000 (216 to 259) |
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| Varenicline vs placebo: number of participants reporting SAEs in duration of trials (trials reporting no events in either group excluded) | Study population (where risk refers to SAEs) | RR 1.25 (1.04 to 1.49) | 15,370 (29 RCTs) | ⊕⊕⊕⊕ HIGH | ||
| 30 per 1000 | 39 per 1000 (32 to 48) | |||||
| Varenicline vs placebo: number of participants reporting cardiac SAEs, including deaths, in duration of trials | Study population (where risk refers to SAEs) | RR 1.36 (0.91 to 2.04) |
8587 (21 studies) | ⊕⊕⊕⊝ MODERATE 4 | ||
| 9 per 1,000 | 12 per 1,000 (8 to 17) |
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| Varenicline vs placebo: number of participants reporting nausea in duration of trials | Study population (where risk refers to SAEs) | RR 3.27 (3.00 to 3.55) |
14963 (32 studies) |
⊕⊕⊕⊕ HIGH | ||
| 85 per 1,000 | 277 per 1,000 (254 to 301) |
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| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).The assumed risk in the comparison group is calculated as the median risk in control groups. CI: Confidence interval; RR: Risk ratio; SAEs: Serious adverse events | ||||||
| GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect | ||||||
1Moderate heterogeneity detected, however all but two studies showed positive effect of varenicline, so did not downgrade on this basis.
2Lack of smaller trials with negative findings suggests possible publication bias. However, earliest studies reported 2006. We are reasonably confident that licensing and subsequent trials have been registered online in clinical trials registries. Thus absence of negative studies may be marker of sustained efficacy rather than suppression or selective management of data.
3Downgraded once as three of the eight studies were rated at high risk of bias due to using an open‐label design.
4Downgraded once due to imprecision; CIs do not rule out an increase in risk