Protocol · graded by use, five uses
Quitting smoking: programs and medicines
Graded on: not smoking at 6 months or longer, biochemically validated where reported.
At a glance
This is about programs and medicines that help people stop smoking. Varenicline, nicotine patches and gum, cytisine and nicotine e-cigarettes all help more people stay off cigarettes for at least 6 months. One large study of a stop-smoking program found fewer deaths over 14 years. A second study pointed the same way but was not certain. Studies that follow people over time find that those who stop before 40 get back most of a lost decade of life.
- What was measured
- Whether people were still not smoking 6 months or more later, usually checked with a breath or saliva test, and in two long trials, how many people died.
- How big
- In one long trial, 21.7% of people in a quit program had stopped smoking at 5 years against 5.4% with usual care, about 163 more per 1,000.Read from the summary of PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 15710956.
- Who it applies to
- Adults who smoked, usually 10 or more cigarettes a day, who wanted to stop. The death results come from middle-aged smokers with mild lung damage. It does not cover pregnancy.
- Safety
- Varenicline led to more serious side effects than dummy pills in pooled trials, while mood and mental health problems were not clearly more common. Nicotine patches and gum can irritate the skin or mouth. Effects of years of e-cigarette use are not known.
- Compared with
- Dummy pills, no medicine, nicotine patches or gum, or usual care.
- Certainty
- Grade B, resting on: Cochrane meta-analyses A study that pools the numbers from several trials into one combined estimate. of randomized trials of quit-smoking medicines, and two randomized trials of quit programs with mortality; cohort studies An observational study that follows a group of people over time and compares what happens to them. described, not graded.
- What would change this grade
- Could rise to A with: Randomized trial of a quit program or medicine against usual care, large enough and long enough to count deaths, run by a group independent of the Lung Health Study. Who: Adults who smoke, without selection for lung disease. Measured: Death from any cause, with heart attack, stroke and lung cancer as second outcomes. Length: At least 10 years of follow-up.
- Cost
- No price recorded yet.
- Sources
- 8 studies cited on this record, listed under Sources.
The B is shared by four of the five uses graded on this record, each on its own evidence. The other one carries its own letter.
This record carries a separate letter for each thing it has been measured on. The headline grade is the best of them, and it does not transfer to the others.
Anthonisen et al. (Ann Intern Med, 2005; PMID 15710956): death from any cause 8.83 against 10.38 per 1,000 person-years over up to 14.5 years (p = 0.03), with 21.7% against 5.4% having stopped at 5 years. Rose and Colwell (J Epidemiol Community Health, 1992; PMID 1573365): total mortality 7% lower over 20 years, not statistically significant Unlikely to be explained by chance alone at the threshold the study set. It says nothing about whether the difference is large enough to matter.. One significant trial and one pointing the same way: C under Rule 06.
Livingstone-Banks et al. (Cochrane, 2023; PMID 37142273): risk ratio 2.32 (2.15 to 2.51) against placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received., 41 trials, high certainty. In EAGLES, 8,144 smokers, varenicline beat placebo, nicotine patch and bupropion on abstinence (Anthenelli et al., Lancet, 2016; PMID 27116918). Replicated The same finding reproduced by a separate research group. A result seen once can be chance or bias; a replicated one is harder to explain away., but quitting stands in for health outcomes: B.
Hartmann-Boyce et al. (Cochrane, 2018; PMID 29852054): any nicotine replacement against control risk ratio 1.55 (1.49 to 1.61), 133 trials, high quality; patch 1.64, gum 1.49, lozenge 1.52, inhaler 1.90, nasal spray 2.02. Replicated, a stand-in outcome: B.
Lindson et al. (Cochrane, 2026; PMID 42642048): risk ratio 1.61 (1.23 to 2.12) against nicotine replacement, 11 trials, high certainty, about 4 more quitters per 100; serious adverse events similar over the trials' follow-up. Effects of years of use are not known. Replicated, a stand-in outcome: B.
Livingstone-Banks et al. (Cochrane, 2023; PMID 37142273): risk ratio 1.30 (1.15 to 1.47) against placebo, 4 trials, moderate certainty, limited by heterogeneity How much the results of the pooled trials differ from each other. High heterogeneity makes a combined estimate less reliable. (I2 83%); against varenicline, no clear difference in 2 trials. A stand-in outcome: B.
Smoking shortens life by about a decade, and in large cohort studies people who stop before 40 recover most of it. Randomized trials test something narrower: whether a program or medicine helps people stop, and whether a program that helps them stop changes how many die. Varenicline, nicotine replacement, cytisine and nicotine e-cigarettes each raise long-term quit rates in pooled trials. One trial of a quit program found fewer deaths over 14.5 years. Graded by use.
Why this letter
Why this gradeThe reasoning, and what the grade does not cover.
Grade B on quitting: varenicline (high certainty, 41 trials), nicotine replacement (high quality, 133 trials), nicotine e-cigarettes against nicotine replacement (high certainty) and cytisine (moderate certainty) each raise the share of people not smoking at 6 months or more in pooled randomized trials (PMIDs 37142273, 29852054, 42642048). Not smoking is the behavior the medicines target and a stand-in for the outcomes that matter, so the letter stops at B. Grade C on death from any cause: one randomized trial of a quit program found it lower over 14.5 years (Lung Health Study; PMID 15710956), and the only other, Whitehall, found it 7% lower over 20 years without reaching significance (PMID 1573365); under Rule 06 one positive trial without independent replication is a C.
WHAT THIS GRADE DOES NOT COVERthe decade of life that cohort studies link to quitting (PMIDs 15213107, 23343063), which describes people who quit rather than the effect of a program and carries no letter under Rule 05; bupropion, which is not graded on this record; heated tobacco and nicotine pouches; and pregnancy, where nicotine replacement trials found a smaller effect that did not last after birth.
A grade describes the human evidence for a named use. It is not advice, and it is not a judgment on any individual prescription. How the letters are decided →
Who responds: this record's trial reading reports no subgroup that identifies who responds.
Evidence notes: randomized trial, meta-analysis, independently replicated
Endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score. graded: Not smoking at 6 months or longer, biochemically validated where reported (surrogate)
Last reviewed: October 2026
The trial that would change this grade.
Positive trials of this shape from independent research groups would move this entry to A.
Why the current trials fall short
The record's B rests on quit rates, a stand-in outcome. A second independent trial finding fewer deaths would replicate the Lung Health Study result (Anthonisen et al., 2005; PMID 15710956) on a hard outcome and could lift the record to A; the only other trial, Whitehall (Rose and Colwell, 1992; PMID 1573365), pointed the same way without reaching significance.
ClinicalTrials.gov, the public registry run by the U.S. National Library of Medicine, lists studies that are recruiting volunteers. The link below searches it for Smoking Cessation among studies recruiting now. EBL has no relationship with any listed study and receives no payment for this link.
Search recruiting studies of Smoking Cessation on ClinicalTrials.gov
Dose, form and timing
Measured in the graded trials: not smoking at 6 months or longer, usually confirmed by exhaled carbon monoxide or cotinine, and in the two program trials, deaths over 14.5 and 20 years.
As studiedDose, form, population and duration for every use.
A grade describes the intervention that was tested. Where the product on the shelf differs from it, this says so.
Safety
Varenicline: more people reported serious adverse events than on placebo (risk ratio 1.23, moderate certainty), with estimates for cardiac events (1.20) and psychiatric events (0.89) too imprecise to settle either way (PMID 37142273); in EAGLES, moderate and severe psychiatric adverse events were not significantly more common than on placebo, including in people with psychiatric disorders (PMID 27116918). Nicotine e-cigarettes: non-serious side effects may be more common than with behavioral support alone, serious events were similar to nicotine replacement over the trials' months of follow-up, and effects of years of use are not known (PMID 42642048). Nicotine replacement: local irritation from patch, gum or spray is the common problem (PMID 29852054).
Cautions documented in human studies. Each caution on this record, sorted by what it rests on.
- Varenicline: more serious adverse events than placebo (risk ratio 1.23), while psychiatric events were not significantly more common in EAGLES (PMID 37142273 PMID 27116918)
- Nicotine e-cigarettes: non-serious side effects may be more common than with behavioral support alone (PMID 42642048)
- Nicotine replacement: local irritation from patch, gum or spray is the common problem (PMID 29852054)
None recorded.
None recorded.
- Long-term e-cigarette use: effects of years of use are not known beyond the trials' months of follow-up
Does not apply: human harm data are listed above.
Grade history
How this letter has changedLatest: No. 386 · October 2026 · First graded.
Varenicline (Livingstone-Banks et al., Cochrane, 2023; PMID 37142273), nicotine replacement (Hartmann-Boyce et al., Cochrane, 2018; PMID 29852054), nicotine e-cigarettes against nicotine replacement (Lindson et al., Cochrane, 2026; PMID 42642048) and cytisine each raise long-term quit rates in pooled randomized trials: B, because not smoking stands in for the outcomes that matter. One randomized trial of a quit program found fewer deaths over 14.5 years (Anthonisen et al., Ann Intern Med, 2005; PMID 15710956), not significantly repeated: C under Rule 06. The decade of life cohort studies link to quitting before 40 (Jha et al., N Engl J Med, 2013; PMID 23343063) is described and carries no letter. Applied the written grade definitions under the editor's standing instruction of October 2026 (Arnold Sandlow, D.C.).PMID 37142273 PMID 29852054 PMID 42642048 PMID 15710956 PMID 23343063
Every change to a letter on this site is dated and published. The full evidence log →
Sources
- Citations
- Every paper cited on this page is matched to its PubMed record on every build.
- Retractions
- None of these papers is retracted or under a journal expression of concern. PubMed is checked again on every build.
- Read against the papers
- October 2026. By the EBL editor, Arnold Sandlow, DC.
- Outside review
- Not yet done. No reviewer outside EBL has checked this record.
What each of these checks can and cannot show: evidence integrity.
The evidence, in fullEight papers, each linked to its PubMed record.
Mortality: Anthonisen et al., Lung Health Study (Ann Intern Med, 2005; PMID 15710956), 5,887 middle-aged smokers with mild airway obstruction at 10 US and Canadian centers, a 10-week program (physician message, 12 group sessions, nicotine gum) against usual care; at 5 years 21.7% against 5.4% had stopped since entry; after up to 14.5 years death from any cause 8.83 against 10.38 per 1,000 person-years (p = 0.03). Rose and Colwell, Whitehall trial (J Epidemiol Community Health, 1992; PMID 1573365), 1,445 male civil servants aged 40 to 59 at high cardiorespiratory risk, anti-smoking advice against normal care; over 20 years total mortality 7% lower, fatal coronary heart disease 13% lower and lung cancer 11% lower. Rates of quitting (abstinence for at least 6 months, biochemically validated where reported): Livingstone-Banks et al. (Cochrane Database Syst Rev, 2023; PMID 37142273), 75 trials, 45,049 people: varenicline against placebo risk ratio 2.32 (2.15 to 2.51; 41 trials, 17,395 people; high certainty), serious adverse events 1.23 (1.01 to 1.48; moderate certainty); cytisine against placebo 1.30 (1.15 to 1.47; 4 trials, 4,623 people; moderate certainty). Hartmann-Boyce et al. (Cochrane Database Syst Rev, 2018; PMID 29852054), 133 trials, 64,640 people: any nicotine replacement against control 1.55 (1.49 to 1.61; high quality). Lindson et al. (Cochrane Database Syst Rev, 2026; PMID 42642048), 80 trials, 29,861 people: nicotine e-cigarettes against nicotine replacement 1.61 (1.23 to 2.12; high certainty), about 4 more quitters per 100. Anthenelli et al., EAGLES (Lancet, 2016; PMID 27116918), 8,144 smokers with and without psychiatric disorders: no significant excess of moderate or severe neuropsychiatric adverse events with varenicline or bupropion against placebo; varenicline odds of abstinence 3.61 against placebo. Observational Research that watches what people already do rather than assigning a treatment. It can show that two things travel together, not that one causes the other., not graded (Rule 05): Doll et al. (BMJ, 2004; PMID 15213107), 50 years of British doctors, stopping at 60, 50, 40 or 30 gained about 3, 6, 9 or 10 years of life expectancy; Jha et al. (N Engl J Med, 2013; PMID 23343063), US adults, smokers lost more than 10 years of life expectancy, and quitting at 25 to 34, 35 to 44 or 45 to 54 gained about 10, 9 and 6 years. The Lung Health Study, Whitehall and the Cochrane reviews were publicly or academically funded; EAGLES was funded by Pfizer and GlaxoSmithKline, makers of varenicline and bupropion.
How EBL searched for the trials (1 search)
The search that was run, what it returned, and what was left out and why, so the absence of evidence can be checked as well as its presence.
smoking cessation[ti] AND "Cochrane Database Syst Rev"[ta] AND (pharmacotherap*[tiab] OR nicotine[tiab] OR varenicline[tiab] OR cytisine[tiab] OR "electronic cigarettes"[tiab])PubMed watch: does a new study change the grade? (nothing new)
No new paper matching the search behind this grade has been added to PubMed since October 2026.
Last run October 2026. A letter on EBL moves only after a logged review. A new paper never moves a letter by arriving: it is read, the answer is written here, and any change to the letter is published in the evidence log.
Disclosure
Educational use only · Not medical advice · EBL grades published human evidence and does not recommend treatment. Stopping a prescription is a decision for your physician.
Evidence Based Longevity, Inc. is owner-operated and edited by Arnold Sandlow, D.C., a California-licensed chiropractor. Evidence Based Longevity publishes in English only · Machine translations are not produced or reviewed by EBL for accuracy
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These statements have not been evaluated by the Food and Drug Administration. Any grade on this page describes the strength of published human trial evidence in the populations studied. It is not a recommendation for any individual and is not medical advice. Starting, stopping or changing any supplement or medication is a decision for your physician.
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