Putting Evidence Into Practice Smoking Cessation

Putting evidence into practice:Smoking cessation

Klara Brunnhuber

K. Michael Cummings

Sheila Feit

Scott Sherman

James Woodcock

Summer 2007

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This report was commissioned by the United Health Foundation.

The BMJ Publishing Group Limited (BMJPG) is a world leader in medicalpublishing. Its journals and online products address major specialties, leadthe debate on health care, and deliver innovative knowledge and bestpractices to doctors, health professionals, researchers and patients, whenand where they need it. The BMJPG publishes BMJ Clinical Evidence, anevidence-based compendium of therapies, which is an authoritative resourcefor informing treatment decisions and improving patient care.

Funding

This report was funded by the United Health Foundation.

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The information contained in this publication is intended for medicalprofessionals.

We rely on studies to confirm the accuracy of the information presented, andto describe generally accepted practices, and therefore we cannot warrant itsaccuracy. Readers should be aware that professionals in the field may havedifferent opinions. Because of this fact and also because of regular advancesin medical research, we strongly recommend that readers independentlyverify specified treatments and drugs, including manufacturers’ guidance.Ultimately, it is the readers’ responsibility to make their own professionaljudgements, so as to appropriately advise and treat their patients.

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Authors

Klara Brunnhuber, MD Clinical Editor, BMJ Publishing Group Limited

K. Michael Cummings, PhD, MPH (Public policy on smoking) Chair, Departmentof Health Behavior, Division of Cancer Prevention and Population Sciences, RoswellPark Cancer Institute, Buffalo, NY

Sheila Feit, MD Deputy Editor, Point of Care, BMJ Publishing Group Limited

Scott Sherman, MD, MPH (Toolkit: 12-step guide to a primary care systemsapproach for smoking cessation) Associate Professor, Department of Medicine, NYUMedical Center, NY

James Woodcock, MSc Product Development Editor, BMJ Publishing GroupLimited

Acknowledgments

Dr Nicholas Gaudin (Head of Communications IARC, WHO, Lyon, France) forproviding pre-publication access to Tobacco Control, Vol. 11: Reversal of Risk AfterQuitting Smoking

Dr Beth Nash (Product Development Manager, BMJ Publishing Group Limited) forher help with planning and reviewing the paper

Sam Martin (Information Specialist, BMJ Publishing Group Limited) and AlexMcNeil (Information Specialist, BMJ Publishing Group Limited) for conductingliterature searches and assisting with appraisal of studies

Polly Brown (Freelance Scientific Editor, BMJ Publishing Group Limited) and DrKaren Devries (PhD, London School of Hygiene and Tropical Medicine) for writingevidence summaries

Tricia Lawrence (Copy Editor, BMJ Publishing Group Limited) for copyediting thepaper

Advisory board and peer review

K. Michael Cummings, PhD, MPH Chair, Department of Health Behavior, Divisionof Cancer Prevention and Population Sciences, Roswell Park Cancer Institute,Buffalo, NY

Michael Fischer, MD, MS Associate Physician in the Division ofPharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital;Instructor in Medicine, Harvard Medical School, Boston, MA

Nancy Rigotti, MD Associate Professor, Department of Medicine, Harvard MedicalSchool; Associate Professor, Department of Health and Social Behavior, HarvardSchool of Public Health; Director, Tobacco Research and Treatment Unit,Massachusetts General Hospital, Boston, MA

Scott Sherman MD, MPH Associate Professor, Department of Medicine, NYUMedical Center, NY

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Additional peer reviewers

Carolyn Dresler, MD, MPA Associate Professor of Health Policy and ManagementDepartment of Health Policy and Management, University of Arkansas for MedicalSciences, Fayetteville, AR

Nancy Lee Clinical Pharmacist, University of California, UCLA Medical Center,Los Angeles, CA

Maria Leon-Roux, MPH Tobacco and Cancer Team, Lifestyle, Environment andCancer Group, IARC, WHO, Lyon, France

Competing interests

K. Michael Cummings, PhD, MPH has been paid by the Pfizer Corporation to givelectures to doctors about their new stop-smoking medication, Chantix. The PfizerCorporation and GlaxoSmithKline have also supported continuing medical education(CME) programs for health care professionals that he has helped to organize. He isco-author of six articles that are referenced in this report.

Carolyn Dresler, MD was the medical director for research and development for theSmoking Control Category (Nicotine replacement products) for GlaxoSmithKlineConsumer Healthcare from June 1998 to June 2004.

Maria Leon-Roux, MPH is one of the officers overseeing a comprehensive reviewreferenced in this report.

Nancy Rigotti, MD has consulted for the Pfizer Corporation and Sanofi-Aventisregarding smoking cessation treatments. The Tobacco Research and Treatment Centerthat she directs has received research grants from the Pfizer Corporation,Sanofi-Aventis, and Nabi Biopharmaceuticals to study smoking cessation treatments.She is co-author of four articles that are referenced in this report.

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Contents

Introduction......................................................................................................................1

Demographics .................................................................................................................2

Disease burden from smoking ........................................................................................3

Health benefits of cessation............................................................................................4

Predictors of quitting and maintained cessation...........................................................12

Public policy on smoking...............................................................................................13

Interventions for smoking cessation..............................................................................15

Economic issues in smoking cessation ........................................................................26

References ....................................................................................................................28

Appendix: Methodology.................................................................................................34

Toolkit: 12-step guide to a primary care systems approach for smokingcessation .......................................................................................................................38

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IntroductionMost smokers want to quit.1 But most attempts fail and new smokers are constantlyrecruited, so about 45 million American adults still smoke.2,3 Cigarette smoking remainsthe single most avoidable cause of death and disability in the United States.2 Sequelaeof smoking include cardiovascular and respiratory disease, cancer (e.g., lung, larynx,esophagus, mouth, bladder, cervix, pancreas, kidneys), and infant deaths related tomaternal smoking.1,2 Increasingly, the dangers of secondhand smoke, such as cardiacdisease and lung cancer, are also recognized by researchers and policy makers.2,4

In the long run, the most effective way to eliminate smoking-related illness is to preventpeople from starting use of tobacco. For those who already smoke, discontinuing use isthe best and surest option for reducing health risks.

+ Motivation to quit smoking is important, but it’s not enough. Most people thinkthey can quit on their own, but although some smokers succeed, most attempts fail.About 40% of smokers stop for at least a day in an attempt to quit each year.3,5 Manyneed encouragement, assistance, and guidance.

+ Smoking can be thought of as a chronic illness, with exacerbations andremissions.6 A brief tobacco use assessment can help identify those people who arehighly nicotine-dependent, or lack motivation and confidence to quit, in order to tailortreatment to individual needs.

+ Medications treat the addiction component of smoking. Drugs are available thatincrease the chance of a successful quit attempt. Trials have generally includedbehavioral support and most have excluded people with serious medical or psychiatricillnesses.

+ Behavioral counseling addresses the habit. Smoking is both a habit and a copingstrategy. Although no method is proven to prevent relapse, patients can try to identifytriggers and plan or rehearse responsive strategies. At follow-up, patients can discussdifficult situations and how to handle them.

+ A systems approach may help to identify and treat smokers. [See Toolkit:12-step guide to a primary care systems approach for smoking cessation] Office visitsand any contact with the health care system (e.g., pregnancy, acute respiratory illness,hospitalization, or pediatric visits) are opportunities to relay smoking cessation informa-tion. Considering smoking status a vital sign can highlight its importance.7 Electronictools may be a promising component of delivering smoking cessation interventionsefficiently.

Encouraging smoking cessation is now recognized as an important part of medical careand public health. This paper will examine the disease burden related to smoking andthe health benefits of quitting. It will present the evidence for interventions to help adultsquit smoking, and provide a practical toolkit for putting the evidence into everydaypractice.

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DemographicsThe prevalence of smoking has decreased by about 50% over the past 50 years toaround one fifth of the U.S. population. Currently about 58% of Americans have neversmoked.

The remainder of the population is about evenly split between former (21%) and current(21%) smokers.8 More men smoke than women (23% vs. 19%). Among people ofdifferent ancestries, smoking is most common among American Indians/NativeAlaskans (33%) and least common among Asians/Pacific Islanders (11.3%) andHispanics (15%). The prevalence of smoking for both blacks and whites is 21%.8

About 22% to 24% of adults aged 18 to 64 are smokers, compared to about 8.8% ofpeople aged 65 or older. Length of education is associated with lower smoking rates,ranging from 26% in people with less than 12 years of education to 10% in those with16 years or more. Therefore, smoking is an important contributor to health disparities.

Smoking rates are higher among young adults (aged 18 to 24) than older ones. Thehighest percentage of young adult smokers is in men with less than 12 years ofeducation (40%). Overall, 26% of young adult men and 22% of young adult womensmoke.8 Smoking is more common among lower socioeconomic groups. About 21% ofpeople at or above the poverty line ($9,645 in 2004) smoke, compared to 29% of thosebelow the poverty line.8

Levels in all of these groups are above the U.S. government’s Healthy People 2010goal: an adult smoking rate of less than 12%.9

Figure 1. Changes in prevalence of smoking among adults in the United States8

2 © BMJ Publishing Group 2007


Disease burden from smokingSmoking is the biggest preventable cause of premature mortality in the United Statesand is a major factor in many diseases and adverse health events, such as cardiovas-cular disease, lung cancer, respiratory diseases and harmful effects on reproduction.Smoking also adversely impacts wound healing in patients who have undergonesurgery. Evidence is still being accumulated for other harms of smoking.

Exposure to secondhand tobacco smoke is a significant health risk for nonsmokers,especially those with pre-existing respiratory and cardiac conditions. Health careprofessionals should routinely question all their patients about exposure to secondhandsmoke and advise their patients to adopt a smoke-free home and car policy.

According to the 2004 Surgeon General’s Report there is sufficient evidence thatsmoking causes the following conditions:10,11

+ Cancers: lung, oral (laryngeal), GI (esophageal, stomach, liver, pancreatic), GU(bladder, kidney, cervical), hematologic (myeloid leukemia)

+ Cardiovascular disease: atherosclerosis, cerebrovascular and coronary heart dis-ease (CHD), abdominal aortic aneurysm

+ Respiratory disease: chronic obstructive pulmonary disease (COPD), increasedsusceptibility to pneumonia, and impaired lung growth during childhood and adoles-cence

+ Reproductive effects: decreased fertility in women, complications of pregnancysuch as premature rupture of the membranes, placenta previa, or placental abruption,miscarriage, still birth, low birth weight, reduced lung function in infants, sudden infantdeath syndrome (SIDS)

+ Other: hip fractures, low bone density, peptic ulcer disease, cataracts, diminishedhealth status

In 2000, smoking was responsible for 269,000 deaths among men and 243,000 deathsamong women in the United States (see figures 2 and 3).

However, many more people are harmed by tobacco use than is indicated by mortalitystatistics. In 2000, an estimated 8.6 (95% CI 6.9 to 10.5) million people in the UnitedStates had disease attributable to smoking.13 For current smokers, chronic bronchitiswas the most prevalent condition (49%), followed by emphysema (24%). For formersmokers, the three most prevalent conditions were chronic bronchitis (26%), emphy-sema (24%), and previous heart attack (24%).



Health benefits of cessationStopping smoking reduces the risk of many of the conditions associated with smoking.However, lag times differ among conditions between smoking and development ofdisease. Although for some conditions the risk falls off quickly after quitting toward thelevel of a never smoker, for others there remains an elevated risk for many decades.

Individual risk often depends on previous duration and intensity of smoking and variesbetween those with and without pre-existing evidence of disease. This means that it isimportant to promote smoking cessation as early as possible among young smokerswho have the greatest chance of avoiding adverse smoking-related events. As thesepopulations are usually in good health and have limited contact with the medicalcommunity, all opportunities need to be taken. Although the largest potential benefits

Figures 2. and 3. Number of deaths attributable to smoking in men and women in 200012



are in young smokers, there are benefits from quitting even among elderly smokers andpeople with considerable comorbidities. These groups should also be encouraged toquit. The best evidence on benefits of cessation comes from a new systematic review bythe International Agency for Research on Cancer (IARC).14

MortalityThere is strong and consistent evidence from cohort and case control studies thatsustained smoking cessation reduces mortality compared with ongoing smoking.

Some of the longest term data has come from 50 years’ follow-up of 34,439 male Britishdoctors.15 This study found a difference in life expectancy of 10 years betweencontinuing smokers and never smokers for men born between 1900 and 1930. There

Figure 4. Timeline of health benefits after smoking cessation14

COPD: chronic obstructive pulmonary disease; CHD: coronary heart disease



were substantial benefits from cessation. Gains in life expectancy were 3 years at age60, 6 years at age 50, 9 years at age 40, and 10 years at age 30.

In the study, overall mortality decreased among nonsmokers over the second half of the20th century. However, as a result of earlier and more intensive smoking, this changewas not observed among cigarette smokers, resulting in an increased smoker tononsmoker death rate ratio.

As Figure 5 shows, cessation is extremely beneficial for all age groups, and the earliersmokers quit, the closer will their chances of survival resemble that of never smokers.

Less good data exist for women, in part because of historically lower smoking levels. Inthe past, female smokers started later and smoked smaller amounts than men, whichmay have produced a lower loss of life. However, this difference increasingly no longerapplies. A population-based cohort study in Norway followed 24,505 women and 25,034men over 26 years and collected smoking status at multiple time points.16 For women, itfound that mortality was approximately halved in smokers who stopped before the ageof 40 compared with continuing smokers (risk of dying in middle age 9.4% vs. 19.4%).Lung cancer rates, which had been adjusted for amount smoked and age started, weresimilar in women and men, but middle-aged women had lower cardiovascular mortalityleading to less all-cause mortality from smoking.

Evidence from observational studies has been supplemented by recent evidence from alarge randomized trial with long-term follow-up that found benefits from cessation eventhough only a minority of the population successfully quit.17 The Lung Health Study in10 clinical centers in the United States and Canada followed 5,887 middle-agedvolunteers with asymptomatic airway obstruction and compared an intensive smokingcessation intervention versus usual care. It found that all-cause mortality was signifi-cantly lower in the intervention group (8.83 per 1000 person-years vs. 10.38 per 1000person-years; P = 0.03).

Cancer riskLung cancer represents the biggest cause of smoking-related cancer mortality. Accord-ing to the Centers for Disease Control and Prevention (CDC), smoking-related lungcancer accounts for more than 10 times the number of years of potential life lost (YLL)in the United States compared with any other smoking-related cancer (based on datafrom 1997 to 2001: 1,113,600 YLL in men and 740,200 YLL in women.10 Because of thetime lag between cigarette smoke-related cell mutation, and disease detection, adifference in lung cancer risk between smokers and former smokers is not to beexpected before around 2 years after quitting. Because of the high relative risk for lungcancer from smoking and the high disease burden, the impact of cessation is relativelyeasy to study. One systematic review found 34 studies with results in men, 21 inwomen, and 6 in both sexes.14 It concluded that most of the increased risk is avoided bythose who stop smoking before middle age, but that there is a smaller but stillsubstantial gain among those who quit in middle or older age. However, the absoluteannual risk of developing or dying from lung cancer does not decrease after stoppingsmoking.

Table 1 summarizes a meta-analysis of U.S. studies for the relative reduction in risk forquitters compared with persistent smokers.14



Figure 5. Impact of smoking and smoking cessation on survival in men15



Table 1. Changes in relative risk (RR) for lung cancer after cessation between former andpersistent smokers14

Years since cessation

< 10 10–19 20–29 30–39

RR in men 0.78 (95% CI0.67–0.92)

0.28 (95% CI0.15–0.51)

0.20 (95% CI0.18–0.22)

0.10 (95% CI0.08–0.13)

RR in women 0.73 (95% CI0.58–0.92)

0.23 (95% CI0.13–0.40)

0.14 (95% CI0.04–0.42)

0.10 (95% CI0.08–0.12)

A systematic review found that smoking cessation was associated with a reduction inthe risk of all the major histologic types of lung cancer.18 However, the risk foradenocarcinoma and large cell carcinoma fell off less rapidly than for small cell lungcancer and squamous cell carcinoma. The subsequent review supported these find-ings.14

As described in Table 2, other types of cancer are also causally linked to smoking.

Table 2. Cancer types other than lung cancer and their association with smoking

Cancer type Disease burden from smoking, additional risk factors, andhealth benefits from cessation

Esophageal cancer + Second biggest cause of years of life lost (YLL) through cancerfrom smoking among men (101,100 YLL), and the third amongwomen (25,000 YLL)

+ Good evidence of reduced risk for ex-smokers compared withcurrent smokers for squamous cell esophageal cancer;14 after 10years of cessation the risk among ex-smokers was still twice therisk of never smokers, and an increased risk was probablymaintained for at least 20 years

+ Evidence on adenocarcinoma was more limited with no clearreduction of risk on cessation.14

Oral cancer + Third biggest cause of years of life lost through cancer amongmen (63,200 YLL) and the fifth among women (19,700 YLL)

+ Strong interaction between alcohol and smoking

+ The best evidence came from a study of 177,903 veterans aged30 years or older. 14,19 It found that former smokers had significantlyless than half (44%) of the risk of current smokers. A recentsystematic review concluded that the risk remained elevatedcompared with never smokers up to 20 years after cessation.14

Pancreatic cancer + Second biggest cause of smoking-related years of life lost fromsmoking among women (51,600 YLL)

+ There is good evidence of risk reduction following cessation.14

The risk is likely to remain elevated for at least 15 years aftercessation.

Urinary tract cancer + There is good evidence of reduced risk among former comparedwith persistent smokers.14 However, the risk remained elevated forat least 25 years after cessation.

Cervical cancer + Following cessation, the relative risk returned rapidly to the levelof never smokers. 20



Stomach cancer + Smoking has recently been found to be causally associated withstomach cancer.

+ Helicobacter pylori infection and alcohol consumption are otherimportant risk factors.

+ Reduced relative risk compared with persistent smokers, butinsufficient evidence to assess whether the risk ever fell to that ofnever smokers.14

Laryngeal cancer + Rapid reduction in risk (about 60% at 10 to 15 years comparedwith persistent smokers), and continuing to fall, although an elevatedrisk remains compared with never smokers for at least 20 years.14

However, caution is warranted as the cohort studies measuredsmoking status only at enrollment.

Myeloid leukemia + Inconclusive evidence to assess the benefits of cessation for therisk of myeloid leukemia.14

A recent study summarized the effects of smoking on cancer treatment efficacy inpeople with malignancies.21 It found that most oncology clinical trials did not collect dataon smoking history and status, particularly in cancers that are not widely acknowledgedas smoking-related. If collected, smoking status was monitored in very few trials andinfrequently reported or included as potential moderator of outcomes. It found thatsmoking was associated with pulmonary complications during and following surgery,poorer wound healing, and increased complications from radiation therapy. Otherstudies have associated smoking cessation with increased survival times in breastcancer and non-small cell lung cancer.22,23,24

Cardiovascular risk

Coronary heart diseaseSmoking operates at different stages in the development of coronary heart disease(CHD). It both reduces the ability of the blood to carry oxygen and causes progressiveatherosclerosis with endothelial injury and thrombotic processes that may lead to acuteinfarction.10,14 A systematic review found that smoking cessation decreased the RR forreinfarction or death by 36% among people with CHD.25 Three subsequent cohortstudies confirmed the benefit from cessation in people with CHD.26–28 The IARC reviewfound some studies showing that RR falls to that of never smokers 10 to 15 years aftercessation, although other studies found that RR was still 10% to 20% elevated 10 to 20years after quitting.14 As a result of possible confounding through misclassification ofsmoking status, reverse causation, and overall healthier behavior by quitters, it is notpossible to assess with the current body of evidence if any long-term residual riskremains.

Cerebrovascular diseaseThe evidence base for association of smoking with cerebrovascular disease is lessgood than for cardiovascular disease. However, it is clear from the IARC review that theRR decreases with cessation and may reach that of never smokers following 5 to 10years of abstinence, although there could still be some elevated risk.14 In part thisprobably depends on past smoking habits, with light smokers (< 20 cigarettes/day)reaching the risk of never smokers within 5 years, whereas heavier smokers may neverreach it.



Peripheral artery diseaseSmoking is the dominant risk factor for peripheral artery disease (PAD). The reduction inRR is slower than for cerebrovascular and CHD, with elevated risk observed even after20 years.14

However, there is evidence of a clearer and more rapid benefit in people with advancedPAD who quit smoking. A meta-analysis of 4 randomized controlled trials (RCTs) and 12prospective studies included in a systematic review found that smoking increased graftfailure 3.09-fold (95% CI 2.34–4.08; P < 0.00001) in people with PAD who wereundergoing arterial reconstructive surgery in the lower extremities, with no difference inpatency rates between autogenous and polyester grafts.29 It demonstrated a clear doseresponse relationship, with reduced patency in heavy smokers compared with moderatesmokers. After quitting, patency failure rates returned to the level of never smokers.

Chronic obstructive pulmonary diseaseThe IARC review found that the general decline in lung function with age reverted tothat of never smokers within 5 years of cessation.14 The strongest evidence for benefitis in people with mild COPD. One RCT, the Lung Health Study, which included peoplewith mild to moderate COPD, found an increase in FEV1 in the first year followingsmoking cessation.30 Subsequently the rate of decline in sustained quitters was halfthat of continuing smokers.31 Limited evidence in people with severe COPD suggestedalso a large benefit.14 Long-term studies suggested a substantial reduction in mortalitycompared with continuing smokers.

The British doctors’ study, after 50 years of observation, found age-standardizedmortality rates per 1000 man-years for COPD of 0.11 for never smokers, 0.64 for formersmokers, and 1.56 for current smokers.15 Given the long time lag between firstsymptoms and death from COPD, reverse causality may lead to underestimatation ofthe benefits of cessation.

Reduced cigarette consumptionAlthough there is good evidence of a dose response effect from smoking from studies ofboth intensity and duration, the evidence on reduced smoking is less clear than theevidence for benefit from smoking cessation on mortality, lung cancer, and cardiovas-cular disease. Recent long-term studies from Norway (24,959 men and 26,251 womenaged 20–49 years) and Denmark (19,732 people with a mean follow-up of 15.5 years)found no evidence of reduced mortality in smokers who reduced smoking.32,33 However,reduced cigarette consumption may be useful as a step toward cessation, with lowercigarette dependency being associated with a greater chance of successful quitting.34

Secondhand smokeSecondhand smoke is now a recognized carcinogen, containing over 50 harmfulchemicals, such as formaldehyde, benzene, vinyl chloride, arsenic, ammonia, andhydrogen cyanide.4 Concentrations of many harmful chemicals are higher in second-hand smoke than in that inhaled by smokers.

Difficulties studying the link between secondhand smoke and disease incidence includethe need to examine large numbers of people for long time lengths, a lack of controlledstudy conditions and recall bias on the part of study participants. However, breathingsecondhand smoke has been found to be immediately detrimental to the cardiovascularsystem.4 There is a prothrombotic effect with increased platelet stickiness, decreased



coronary flow reserves, and reduced heart rate variability. Pooled evidence hasindicated a causal relationship between secondhand smoke and both lung cancer andCHD. Nonsmokers exposed to secondhand smoke at home or at work have about a25% to 30% increased risk of heart disease and 20% to 30% increased risk of lungcancer.

A recent systematic review and meta-analysis looked specifically at workplace expo-sure to tobacco smoke, excluding studies that featured former smokers.35 The analysisstratified studies depending on level of exposure and weighted evidence on several keyissues including geographic location, gender, and level of exposure to other lungcarcinogens such as coal heating fumes. Most of the included studies (20 of 25) foundan increased lung cancer risk among never smokers exposed to workplace secondhandsmoke. Meta-analysis found that relative risk increased on average by 24%, with peoplein the highest workplace exposure categories being twice as likely to develop lungcancer compared with nonexposed people.

Despite declining smoking rates, millions of Americans continue to be exposed tosecondhand smoke, including 60% of children aged 3 to 11 years.4 Millions of indoorworkers are still not covered by smoke-free workplace rules. Secondhand smokeexposure varies by occupation, gender, and ethnicity, but exposure tends to be higher inlower socioeconomic groups. People who work in entertainment jobs, restaurants, orbars are at highest risk. Homes and vehicles also remain important places of exposure.

Infants and young children are considered especially vulnerable. Maternal exposureduring pregnancy is associated with a small decrease in birth weight and persistentadverse effects on lung function throughout childhood. Parental smoke is linked to everhaving asthma, and exposure in children has been associated with increased risk forsudden infant death syndrome (SIDS), acute respiratory infections, ear problems, andincreased severity of asthma.

The Surgeon General has concluded that there is no safe level for secondhand smokeexposure. Mechanical ventilation or separation of smokers does not fully eliminate therisk. Air cleaning systems leave behind small particles. Heating and cooling systemsmay distribute smoke throughout a building.

A final frontier is the restriction of smoking in cars and homes. Custody and fosterarrangements may be affected by parental smoking; some residential buildings are nowsmoke-free; and, a few regions have introduced fines for smoking in cars withchildren.4,36,37



Predictors of quitting and maintained cessationThere are two aspects to cessation: making a quit attempt and maintaining cessation.Two prospective studies (including over 13,000 smokers) found that nicotine depend-ence was the key predictor of cessation success, as assessed by length of time to firstcigarette of the day and number of cigarettes smoked per day.34,38

Table 3. Predictors of quit attempts and cessation success

Predictive factor Definition Increased quitattempts

Increased cessa-tion success

Low nicotinedependence34,38,39

Low Heaviness of SmokingIndex (variable of number ofcigarettes smoked per dayand time to first cigarette) orsmoking less than daily

+ +

High motivation34,38,39 Quit date set or strongdesire to quit

+ Small effect

Longer prior attempt38,39 Longest time off smoking inthe past ≥6 months

+ +

Prior quit attempts38,39 Tried to quit during previousyear

+ –

Higher socioeconomicstatus34

Assessed by length ofeducation or income

+ +

Initial success38,40 No smoking within 2 weeksof attempt

No data +

Gender as a predictor of successThe recent International Tobacco Control (ITC) Four Country Survey and the Commu-nity Intervention Trial for Smoking Cessation (COMMIT) trial found some evidence forhigher successful cessation rates among men.34,38,39 However, a systematic review didnot show that the relative benefits of different smoking cessation interventions varied bysex.41



Public policy on smokingEfforts to increase smoking cessation at the population level involve interventions thatconvince smokers to make quit attempts, and encourage those who do try to quit to usetreatments that will increase their odds of staying quit.42 Fortunately, effective treat-ments for tobacco use are available, with several new treatments in the pipeline.43

However, the potential impact of current and emerging treatments for tobacco use willdepend not only on their efficacy, but also the extent to which these treatments reachthose who might benefit from them.

Not much evidence is available to support the idea that therapies for treating tobaccouse have dramatically influenced rates of smoking on a population level.44 The mainreason for this failure is the generally low utilization of these therapies, which is in partthe result of a need for health care workers to more aggressively assist theirtobacco-using patients in quitting. Health care providers have an important role to playin creating practice environments that promote cessation treatment as part of routinecare.45 Medicare currently covers cessation counseling benefits, and its prescriptiondrug benefit (Part D) plan also covers smoking cessation treatments, though notover-the-counter (OTC) products such as nicotine patches and gum.46,47 Other strate-gies that can increase the reach, appeal, and use of effective interventions include thepromotion of a national quit line number on cigarette packs and the availability of moreconsumer-appealing cessation treatments.46,47 These hold great untapped potential toreduce overall adult smoking prevalence and growing disparities in tobacco use in thefuture.

Interventions that have the greatest chance of reducing tobacco use in the populationare those that reach the most smokers. This is one of the reasons why past researchhas shown that the most potent demand-reducing influences on tobacco use have beeninterventions that impact all smokers repeatedly, such as higher taxes on tobaccoproducts, comprehensive advertising bans, pack warnings, hard-hitting anti-tobaccoeducation campaigns, and smoke-free policies.48–50 Studies have found that reward-based (quit and win) campaigns may increase quit rates, but misreporting cessationmakes studying them difficult.51

Smoking is more widespread among lower socioeconomic groups and is a majorcontributor to health inequities. This means successful cessation can be more difficultas a result of greater exposure to cues for smoking. Furthermore, low-income smokersmay have lower access to pharmacotherapy and other treatments that improvecessation. A systematic review looked at the effect of reducing the cost of smokingcessation treatments for smokers.52 A meta-analysis of four studies found that such apolicy helped an additional 2% (95% CI 0–5%) of smokers to quit. One largesubsequent controlled study found that sending free nicotine replacement therapy tosmokers who called a quit line substantially increased cessation.53 Similarly, anotherrecent trial found that giving away vouchers for nicotine replacement therapy (NRT) tosmokers as part of a broader campaign increased quit rates,54 although a study of NRTand telephone counseling found no benefit.55 Moreover, population-based studies havefound that women with low educational levels were particularly responsive to mediamessages and were more sensitive to price increases than more educated women(elasticity near 1 for the period 1992 to 2002, implying that a 10% increase in pricewould reduce smoking by 10%).56

Comprehensive tobacco control measures can prove effective across the population.California was the first U.S. state to begin a comprehensive tobacco control program,



including price increases and mass media campaigns, and spent considerably morethan other states per head on tobacco control during the 1990s. This resulted in higherrates of cessation among younger and to a lesser extent middle-aged smokers than inother states.57 In New York, increased cigarette taxes, smoke-free legislation, increasedprovision of cessation services, including a free nicotine patch program, and educationwere credited with reducing the prevalence of smoking, which fell from 21.6% to 19.2%during 2002 and 2003, across both sexes and among all age groups, ethnicities, andeducational levels.48 The study found that increased taxation accounted for most of thereduction, although out-of-state purchase of tobacco reduced the benefit.

Simulation modeling found that the largest reductions in smoking prevalence in theUnited States between 1993 and 2003 have come from price increases, because otherinterventions have not been implemented to the degree necessary to achieve majorchange.58 Projections predict that a total smoking ban in workplaces, restaurants, andpublic places would reduce the prevalence of smoking by 3.4% by 2010.

In May 2007, the Institute of Medicine (part of the National Academy of Sciences)issued a report recommending a two-pronged approach to reducing tobacco use in theUnited States.59 The first proposed step was to strengthen traditional tobacco controlmeasures and the second to change the current regulatory landscape. The Institutesupported local efforts, but also advised giving regulatory authority to a federal agencysuch as the U.S. Food and Drug Administration (FDA). Suggested actions includedstepped-up health warnings, limitations on advertising, increased funding and coordina-tion of state activities, decreased nicotine content of cigarettes, higher tobacco taxes,and a national ban on indoor smoking.

In order to establish an environment conducive to reducing tobacco use, over 140countries have ratified the Framework Convention on Tobacco Control (FCTC), which isthe first global health treaty negotiated under the auspices of the World HealthOrganization (WHO). The FCTC commits countries to implement a comprehensiverange of policies (see table 4).60

Table 4. Key policy provisions of the Framework Convention on Tobacco Control (FCTC)

+ Increase tobacco taxes+ Protect citizens from exposure to tobacco smoke in workplaces, public transport, and indoor public

places+ Enact comprehensive bans on tobacco advertising, promotion, and sponsorship+ Regulate the packaging and labeling of tobacco products to prevent the use of misleading and

deceptive terms such as light and mild+ Regulate the packaging and labeling of tobacco products to ensure appropriate product warnings

are communicated to consumers; for example, obligate the placement of rotating health warningson tobacco packaging that cover at least 30% (but ideally 50% or more) of the principal displayareas and include pictures or pictograms

+ Regulate the testing and disclosure of the content and emissions of tobacco products+ Promote public awareness of tobacco control issues by ensuring broad access to effective

comprehensive educational and public awareness programs on the health risks of tobacco andexposure to tobacco smoke

+ Promote and implement effective programs aimed at promoting the cessation of tobacco use+ Combat smuggling, including the placing of final destination markings on packs+ Implement legislation and programs to prohibit the sale of tobacco products to minors+ Implement policies to support economically viable alternative sources of income for tobacco

workers, growers, and individual sellers



Interventions for smoking cessation

Effectiveness of drug treatmentsBoth nicotine- and nonnicotine-based therapies can increase the chances of successfulsmoking cessation.61 Nicotine-based therapies are available as transdermal patch,gum, nasal spray, inhaler, or lozenge. FDA-approved nonnicotine-based drug treat-ments include bupropion and varenicline.

Other effective drugs include nortriptyline or clonidine, but side effects may limit theiruse.

Table 5. Comparison of FDA-approved drug therapies for smoking cessation

Mechanism ofaction

Efficacy compared with:

placebo orcontroltherapy

NRT* bupropion varenicline

NRT Reducesnicotinewithdrawalsymptoms

NRTincreasesodds ofsmokingcessation1.5- to2-fold.62

N/A NRT andbupropionseem equallyefficacious 63

No RCTs

Bupro-pion

Antidepressantor independentneurologiceffects64

Bupropionincreasesodds ofsmokingcessation2-fold.64

Bupropionand NRTseem equallyefficacious63

N/A Vareniclineincreasesodds ofsmokingcessationabout1.7-foldcompared tobupropion**65

Vareni-cline

Partial nicotinereceptor agonist

Vareniclineincreasesodds ofsmokingcessation3-fold**65

No RCTs Vareniclineincreasesodds ofsmokingcessationabout 1.7-foldcompared tobupropion**65

N/A

* NRT: nicotine replacement therapy

** All studies included in this systematic review, although of high quality, receivedindustry funding from the varenicline manufacturer Pfizer.65

Nicotine replacementNicotine replacement therapy (NRT) reduces the withdrawal symptoms associated withsmoking cessation, such as anger, anxiety, craving, difficulty concentrating, hunger,impatience, or restlessness.6,62,66

Two recent high-quality systematic reviews found all forms of NRT to be effective.6,62

The first review, with follow-up of at least 6 months, found that NRT achieved an overall



abstinence rate of about 17% compared with 10% in the control groups.62 However,there was considerable variation in control group abstinence rates, depending on thelength of follow-up, how cessation was assessed, and the population included in thetrial. The second review looked at a follow-up of more than 1 year after the start oftreatment.6 Relative efficacy of NRT over and above placebo fell from 11% at 1 year to7% at an average of 4.3 years of follow-up. Relapse rates did not differ between NRTand control groups over time or depend upon length of initial NRT treatment or length offinal follow-up. The low relapse rates after the second year showed that NRT had apermanent effect on smoking cessation. However, using only 6 to 12 months of results,as usually reported in reviews and guidelines, will result in overestimating the lifetimebenefits and cost savings from NRT by about 30%.

The first review observed that the main factor determining the effectiveness of NRT onquit rates was the level of nicotine dependence.62 It found little good evidence that NRTwas effective for people who smoke fewer than 10 to 15 cigarettes daily. An additionalcohort study found that nicotine patches were more effective in achieving long-termcessation (52 weeks) in smokers with moderate nicotine dependence compared withthose with mild or high dependence.40

The review found no evidence that one form of NRT is preferable or that additionalcounseling offered any benefit, although most trials of NRT have included some type ofnonpharmacologic support.6,62 An additional trial looked at nicotine patches comparedwith nasal spray and found no significant difference in abstinence between the twotreatments at 6 months.67 However, it found that positive predictors for the patch weredifferent compared with the nasal spray: low to moderate dependency smokers withwhite ancestry and a BMI less than 30 kg/m2 were more successful with the patch,whereas highly dependent obese people from a nonwhite background had highercessation rates with the spray. Another trial compared four different formats of NRT andfound that women were more successful with inhaler compared with gum and men viceversa.68

Side effects of NRT include local irritation, the manifestation of which depends on routeof administration. NRT appears to be generally safe in patients with a history of stablecardiovascular disease.62 As a result of concerns regarding the sympathomimeticeffects of nicotine, most studies have excluded people with unstable cardiac disease.NRT has an FDA Category D rating in pregnancy.69

Higher doses of the patch (> 22 mg/day or > 15 mg/16 hours) may be slightly moreefficacious than standard dosage. One multicenter European trial, which looked athigher doses and longer durations of treatment, also found increased 1-year successrates associated with a higher dose patch, but treatment beyond 8 to 12 weeks did notimprove efficacy.70 Higher doses may be useful for heavy smokers (≥ 30 cigarettes/day)or patients relapsing with withdrawal symptoms on standard dosage.62

Patient preference, costs, or side effects may be considerations when choosing NRT. Incurrent clinical practice, the patch, with its long-acting effect because of stable nicotineblood levels, is generally used as the base product, with other shorter-acting formsused as add-ons.



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Combination NRTThere is weak evidence that combination NRT may be more effective than singleforms.62 Overall, abstinence rates were 1.4-fold higher with combination than mono-therapy. Possible benefits include sensory effects of multiple delivery systems, highernicotine substitution, or other factors.84

Table 7. One-year abstinence rates with combined NRT delivery *

Combination used Combinationtherapy

Monotherapy orno therapy

P value Abstinence rates

Patch + gum vs.patch alone

18% 13% 0.2 Significantly higherwith combination earlyon, but no significantdifference betweengroups at 1 year62

Patch + gum vs.gum alone

24% 17% 0.2 Significantly higherwith combination at12 weeks; trendcontinued but nosignificant differencebetween groups at 1year62

Patch + nasal sprayvs. patch alone

27% 11% 0.002 Significantly higherwith combination at 1year62

16% (at 6 years) 9% (at 6 years) 0.077 Trend continued butno significantdifference betweengroups at 6 years85

Patch + nasal sprayvs. either alone

9.1% (at 6months)

+ 7.8% (patch)+ 6.9% (spray)(at 6 months)

0.3 No significantdifference betweengroups at 6 months62

Patch + inhaler vs.inhaler alone

19.5% 14% 0.1 Significantly higherwith combination at12 weeks; trendcontinued but nosignificant differencebetween groups at 1year62

Patch + inhaler vs.either alone

3% 7% 0.2 No significantdifference betweengroups at 1 year62

Patch + inhaler vs.no therapy

15% 14% 0.8 No significantdifference betweengroups at 1 year62



*based on trials including 100 to 500 smokers; exceptions to 1-year time frame noted intable

Combining NRT with other drug treatmentsTwo small studies suggest that adding mecamylamine, a nicotine receptor antagonist,to NRT may be superior to NRT alone.86 A benefit from adding antidepressants to NRThas not been shown.64 The opioid antagonist naltrexone is under investigation as anadjunct to treatment such as NRT and may attenuate smoking cessation-associatedweight gain.87–89

There is no good evidence about combining NRT with varenicline, anxiolytics, orclonidine.

Adding NRT to nondrug therapyAlthough the absolute chances of quitting increase when NRT is used in conjunctionwith additional support, a systematic review found the relative benefit of NRT to bemostly independent of length of therapy, intensity of other support, or setting in whichNRT was given.62 One trial showed that NRT plus physician training improved quit ratesover physician training alone.90

AntidepressantsMonotherapy with either bupropion or nortriptyline approximately doubles the odds ofsmoking cessation at 6 months.64 Bupropion is a selective serotonin/norepinephrineuptake inhibitor (SSNRI) and nortriptyline is a tricyclic antidepressant (TCA).

Possible, but unproven, mechanisms of action include:

+ improving depressive symptoms precipitated by quitting smoking

+ substituting for possible antidepressant effects of nicotine

+ independent neurologic effect(s), such as nicotine receptor antagonism.

Bupropion has been shown to be effective in varied populations and settings, in peoplewith and without depression, and in combination with different types of behavioralsupport. A recent trial has shown it to be effective and safe in people with acutecardiovascular disease.91 It decreases depressive symptoms in highly nicotine-dependent smokers, but symptoms rebound when bupropion is discontinued.92

Extended therapy with bupropion to prevent relapse has not been found to bebeneficial.64 Nortriptyline has been studied in fewer trials than bupropion. Bupropionand nortriptyline appear to be about equally efficacious with NRT, but direct compari-sons are few.63 There is also insufficient evidence about combining an antidepressantand NRT. One small trial found that bupropion was associated with higher smokingcessation rates at 6 months compared with nortriptyline or placebo when each wasadded to intensive counseling therapy.93 Initial trials suggest that bupropion may be lessefficacious than varenicline, although so far all relevant high-quality trials have receivedindustry funding from varenicline’s manufacturer.65

Since May 2006, bupropion has an FDA Pregnancy Category C rating. As for manyolder drugs, nortriptyline has not been rated by its manufacturer but has receivedPregnancy Category C listings.94,95

One cohort study of predictors of abstinence in people who were receiving long-termsustained release bupropion, found that older age and minimal early weight gain were



positive predictive factors for long-term abstinence (52 weeks).96 One randomizedcontrol trial found that risk factors for relapse in people treated with bupropion andcounseling (in varying dosages and intensities) were younger age, female sex, highlevels of nicotine dependence, shorter previous quit attempts, previous use of NRT, andself-reported depression.97 One cohort study looked at bupropion and nicotine patchesin combination and concluded that positive predictive factors for continued abstinenceat 1 year were:98

+ Absent history of COPD

+ Having effectively quit after the first week of treatment

+ In people with COPD: lower value for mid-range forced expiratory flow (FEF 25–75)

Antidepressants such as selective serotonin uptake inhibitors (SSRIs) or monoamineoxidase (MAO) inhibitors have not been shown to help smoking cessation.64,99,100,101

Nicotine partial receptor agonistsVarenicline increases smoking cessation approximately 3-fold at 1 year compared withplacebo.65,102 It is not clear whether further lengthening the duration of therapy would bebeneficial or whether varenicline may help prevent relapse.103,60

A systematic review found that compared with bupropion, varenicline increased theodds of smoking cessation approximately 1.7-fold at 1 year, although this result isbased on studies that have received industry funding.65 The main side effect has beennausea, which usually improves over time.60,104 Direct comparisons with NRT arelacking.

Varenicline has been given an FDA Pregnancy Category C rating.

Cytisine is the natural chemical from which varenicline was developed. Like varenicline,it works as a nicotine partial receptor agonist, but has a considerably lower price. It iscurrently only available in Europe, is less well studied but may also aid smokingcessation.105

There have been no good quality trials about a third partial nicotine agonist, lobeline.106

Table 8. Nonnicotine drugs for smoking cessation

FDA-approvedfor indica-

tion

Dose Side effects

Bupropion SR √ + Set target quit datefor during second weekof treatment.+ 150 mg daily x 3days, then 150 mg twicedaily+ Continue treatmenttotal 7–12 weeks107

+ Dry mouth, sedation 108,109

+ Seizure (1/1000 when used forsmoking cessation)64

+ Has not been linked toincreased risk of suicide,64 but allantidepressants are labeled with aBlack Box warning about possiblyincreased risk

Nortriptyline + Total dosage instudies has generallybeen 75–100 mg dailyfor 6–12 weeks64

+ Sedation, constipation, urinaryretention, risk of arrhythmia64



FDA-approvedfor indica-

tion

Dose Side effects

Varenicline √ + Set a target quit datefor 1 week after startingtreatment+ 0.5 mg once daily for3 days then twice dailydays 4–7+ Increase to 1 mgtwice daily from day 8through end of 12 weekstotal therapy104

+ Nausea, sleep disturbances,headache60,104

Other drug therapies

+ Clonidine, a centrally acting antihypertensive agent, has been studied mostly inconjunction with behavioral counseling. Based on limited data, it increased smokingcessation approximately 2-fold, but had side effects, especially dry mouth and sedation,which limit its use.108 Tapering of dosing at the end of therapy is recommended to avoidwithdrawal effects of clonidine.69,110 Hypertensive patients in particular are at risk forrebound hypertension upon abrupt cessation.

+ Limited evidence from four trials identified by a systematic review found no significantlong-term benefit for smoking cessation from the opioid antagonist naltrexone com-pared with placebo.87 Adding naltrexone to NRT did not attenuate weight gain insmoking cessation. However, the confidence intervals were compatible with bothclinically significant benefit and possible negative effect (OR 1.26, 95% CI 0.80–2.01).

+ There have been no systematic reviews or good quality trials evaluating the efficacyof rimonabant (a CB1 cannabinoid receptor antagonist) for smoking cessation. It ismarketed in Europe, but in June 2007 the FDA refused approval for its use as a weightloss aid, based on concern about psychiatric side effects.

+ Silver acetate gum, lozenge, or spray causes an unpleasant taste when combinedwith cigarettes.111 Limited data do not support a role for it, possibly because ofreportedly poor compliance.

+ There is no consistent evidence that anxiolytics aid smoking cessation.112 In onetrial, buspirone improved smoking abstinence in high-anxiety smokers, but only for theduration of therapy.113

OTC devices and aids for smoking cessationMany smoking cessation devices or aids are sold OTC in the United States. If notspecifically marketed as a cessation tool, they may bypass regulatory oversight and arenot regulated by the FDA. Products include smokeless inhalers, nicotine filteringdevices, and a water-soluble gel containing tobacco extracts. We found no high-qualityevidence that these products work.

Under investigation: Nicotine conjugate vaccineThe purpose of current drug therapies for smoking cessation is to either replacenicotine from cigarettes with nicotine in safer forms or try to otherwise reduce



withdrawal symptoms. A vaccine currently in development aims to induce nicotine-specific antibodies in order to prevent nicotine’s passage into the brain.114 Vaccine isconjugated because ordinarily nicotine is a small, nonimmunogenic molecule. In onesmall study, patients received either a nicotine conjugate vaccine given as one of 3doses (50, 100, or 200 µg) intramuscularly or placebo at approximately 0, 1, 2, and 6months.115 Vaccine immunogenicity and 30-day abstinence rates were dose-related.Nicotine conjugate vaccine is currently in Phase IIb trials in the United States butachieving adequate antibody response and duration of antibodies remain challenges inits development.

Effectiveness of nondrug treatments for smoking cessationNonpharmacologic measures can be used singly, in combination, or along with drugtherapies. There is good evidence that combining brief practical advice to quit withpharmacotherapy increases success rates. Similarly, delivery systems such as doctorcounseling and/or quit lines with access to drug treatments are significantly moreeffective than nondrug treatments alone.

+ Self-help materials and brief advice both increase the chances of smokingcessation. The benefit per patient is low, but because of the high number of contactswith health care professionals, self-help materials and brief advice both offer animportant opportunity to promote cessation with potentially large population effects.However, self-help materials may not offer additional benefit when more intensiveinterventions are used.

+ Individual, group, and telephone counseling are effective at a patient level andare recommended for those willing to accept them. When provided with NRT, individualcounseling offers a lower relative benefit than on its own, but the absolute benefit maybe similar. Self-help materials and group behavioral counseling may not offer additionalbenefit when added to NRT.

+ Internet- and computer-based programs may offer some benefit, but moreresearch is needed to identify effective programs.

+ Exercise reduces symptoms of withdrawal. Although evidence for long-term cessa-tion is less clear, given the additional benefits, it can be recommended.

+ There is no good evidence that biomedical risk assessment, hypnotherapy, oracupuncture increase cessation.

+ Providing telephone quit lines increases cessation.

+ It is not clear which interventions reduce relapse.

+ The effectiveness of rapid (aversive) smoking is unproven.

Training health professionals may offer some benefit, particularly if the importance offollow-up is emphasized.



Table 9. Nondrug treatments for smoking cessation

Intervention Evidence Clinical implications

Self-helpmaterials

+ In one review, self-help materials, whether tailored ornot, increased long-term abstinence about 1.5-foldcompared with no intervention (absolute differenceabout 2%).116 Tailored materials might be more effectivethan standard materials, but the evidence was notconclusive.+ However, there was no evidence that self-helpmaterials would be of benefit when added to NRT orface-to-face contact.

+ Self-help materials are aneasy intervention, and shouldbe readily available in theoffice and offered to allsmokers.

Brief advice + In one review, brief advice increased the odds ofquitting approximately 1.7-fold (absolute increase ofabout 2.5%) compared with no advice (or usual care).117

+ The absolute benefit in trials of brief advice is lowerthan in trials involving highly motivated people.+ There appeared to be a small advantage of intensiveadvice (longer, defined as > 20 minutes, more visits, ora self-help manual) over minimal advice.+ There is possibly a small benefit to follow-up visits.+ The review did not look at potential harms fromphysician counseling.

+ Any interaction with ahealth care professional is anopportunity to provide briefadvice. Most studies havebeen conducted in a primarycare setting.117 Brief advicemay be given by a physicianor nurse.+ Brief advice is an easyintervention and has thepotential to have a largepopulation impact.+ Forty smokers wouldneed to be given intensiverather than minimal advice toproduce one extra quitterafter 6 to 12 months.

Individualcounseling

+ One review found that individual counseling bynurses increased quit rates about 1.5-fold.118 NRT usein the trials varied considerably. Nurse counselingoffered a larger relative benefit for inpatients withcardiovascular disease and when offered as part ofcardiac rehabilitation, whereas there was no evidence ofbenefit in other hospitalized smokers.+ One recent subsequent UK trial found no significantdifference between basic and weekly support added toNRT.119

+ Individual counseling byphysicians seems to be mosteffective, followed bymultidisciplinary teams,dentists, and nurses.120

Smokingcessationcounselor

+ One review found that individual counseling by atrained smoking cessation counselor providing one ormore face-to-face sessions outside of usual careincreased cessation about 1.5-fold.121 Although therelative benefit appeared lower when used inconjunction with NRT, the absolute benefit appeared tobe similar in trials with and without NRT.+ The review found no evidence that intensivecounseling was more effective than shorter sessions,although the evidence was not conclusive. The reviewdid not report on harms.+ One subsequent trial found that individual counseling(primarily in person but allowing phone counseling) wasmore effective than advice and minimal support forabstinence at 6 months.122

+ Another subsequent RCT found 5-fold highercessation after 6 and 12 months with motivationalinterviewing than with brief advice.123

+ Most trials wereconducted with inpatients.121




Telephonecounseling

+ One recent systematic review found that smokerswho received additional call back counseling afterphoning a quit line were about 1.4-fold more likely toquit (absolute difference about 3%).124 Similar resultswere found for telephone counseling not initiated bycalls to help lines. The study suggested that increasingthe number of calls increased the benefit.+ There was a small benefit from adding telephonecounseling to NRT.+ The number of calls, their content, and durationvaried considerably between different quit lines.

+ A meta-analysissuggested that younger,male, light smokersbenefited the most fromtelephone counselinginitiated by health carepersonnel and added to otherminimal interventions.125

Telephone quitlines

+ One review found limited evidence that providing atelephone hotline helped 1 in 50 extra smokers toquit.124

Internet + In early studies, mailing computer-generatedfeedback reports was associated with improved quitrates.126 It is not yet clear how well more recentinteractive computer systems work.+ Among visitors to a smoking cessation website,counseling letters and email reminders based onpsychological and addiction theory, which includeinformation on health risks and coping strategies, maybe more effective than a shorter program with moreinformation on nicotine replacement therapy andnicotine dependence127

+ More research is neededabout which patients benefit,how to add internet to otherinterventions and use of theinternet in sophisticated orinteractive ways.126

Group behaviortherapy

+ In one review, group programs were about twice aseffective as self-help programs or no intervention.128

+ The evidence is not conclusive on how groupprograms compare with individual counseling.+ The review suggested that adding group behaviortherapy to NRT provided no additional benefit, but thecontrol groups included behavioral components that mayhave affected the results.

+ Patient acceptance ofgroup therapy may vary.128

+ Evidence is lacking aboutspecific psychologicalmethods aside from usualsupport.+ Cost effectivenesscompared with individualcounseling is not clear.

Exercise + A single session of exercise seems to temporarilyreduce cigarette craving,129 but a systematic reviewfound only weak evidence that exercise improved quitrates, alone or added to a smoking cessationprogram.130

+ One trial identified by the systematic reviewsuggested that adding exercise to NRT may be ofbenefit.

+ Studies have been smalland heterogeneous.130

+ Exercise reducespost-smoking cessationweight-gain.131

+ Even with weak evidenceof effectiveness of increasedsmoking cessation, exerciseoffers a wide range of otherbenefits.

Biomedical riskassessment

+ Evidence is limited about biomedical risk assessment(e.g., exhaled carbon monoxide, spirometry).132

+ More research is neededto evaluate the efficacy ofbiomedical risk assessment.

Complementaryinterventions

+ There is no evidence that hypnotherapy,133

acupuncture, acupressure, laser therapy, orelectrostimulation help quit rates.134,135

+ These measures cannotbe recommended forsmoking cessation on thebasis of current evidence.




Nondrugtreatments forrelapseprevention

+ There is no evidence that skills training (e.g.,avoidance of triggers) or other specific interventionsprevent relapse136,137

+ The studies in one review mostly included only briefor written interventions, so a benefit from more intensiveface-to-face contact can not be excluded.136

+ Many patients relapse,thus effective strategies aregreatly needed.136

Aversivesmoking

+ The available evidence does not allow determinationof the effectiveness of rapid (aversive) smoking.138

+ There is sufficientindication of promise towarrant further evaluation ofthis technique.138

Interventions aimed at health professionals

+ Training health professionals on a group basis and offering prompts may increase thechance of smoking cessation interventions being offered to patients.62,117

+ In one review, prompts increased how often smoking cessation interventions wereoffered. It is not clear if this improves quit rates.90 The trial with the most promisingresult emphasized follow-up more than other trials and physicians were paid forfollow-up visits.

Another review found limited evidence that tools (e.g., questionnaires, chart stickers,checklists, flow charts, reminder letters) and teamwork increased rates and effective-ness of counseling and increased quit rates.139

[See Toolkit: 12-step guide to a primary care systems approach for smoking cessation]



Economic issues in smoking cessationThe massive toll of smoking measured in morbidity and mortality is reflected in a largeeconomic burden on society. In the United States, this has been estimated for 1998 at$75.5 billion in health care costs alone. Beyond this, there are costs in terms of lostproductivity estimated at $81.9 billion as the annual average between 1995 and1999.140 Smoking cessation can reduce some of this burden and studies haveconsistently found that effective interventions for smoking cessation are cost effective.

However, assessing cost effectiveness can be difficult because of variations in studypopulations and their motivation to quit, as well as extrapolation of relapse rates andbaseline cessation rates. For those populations without pre-existing disease, thebenefits may be measurable only decades down the line. This makes calculationsparticularly sensitive to how future costs and benefits are discounted.

Cost effectiveness of smoking cessation can be analyzed from the perspective of theindividual, the health provider or society. The individual saves through reduced expendi-ture on cigarettes, lower private health care costs, and increased income. The healthindustry benefits from reduced expenditure attributable to both primary and second-hand smoke, whereas society profits from increased productivity, reduced cost ofcleaning up after smokers, and fewer smoking-related fires.

Studies have approached these issues in different ways and are not always clear abouttheir perspective and which costs they have included. Furthermore, the outcomemeasures in clinical studies of cessation are varied and sometimes difficult to assess.Results based on these measures provide a key input into cost-effectiveness analyses,which makes it hard to reach and interpret definitive conclusions. This has notsupported informed decision making. A systematic review of cost-effectiveness studiesof smoking cessation recalculated the cost effectiveness from a societal perspective(using Dutch price levels but in U.S. dollars) and found that standardizing the measuresused in studies often increased the cost-effectiveness ratios substantially.141 Despitethis, smoking interventions still remained clearly cost effective. The review identified aself-help manual written for a specific subgroup of pregnant women as the mostcost-effective intervention, with a cost of $0 per year of life saved. It found thatcounseling or self help (with smokers choosing between them) cost $2340 per year oflife saved, whereas NRT plus counseling cost $8794. Although the least intensiveinterventions may offer the best cost effectiveness ratio, their low cost and the extremelylarge potential gains do not mean they should be selected in preference to moreintensive interventions. These interventions do not have large effects and the extrainvestment in intensive interventions can achieve additional benefit and offer a superiorreturn compared with many interventions that are routinely paid for in other fields.

A review looking at U.S. cost effectiveness from a third-party payer perspective foundthat in 2003, the cost per year of life saved with nicotine treatments and bupropionacross different age groups fell substantially below the generally accepted thresholdsfor cost effectiveness in the United States.142



Table 10. Cost per life year saved for different drug therapies by age in the United States in2003.142

Cost per year of life saved by age group ($)

Agegroup

(years)

Nicotine replacement Bupropion

Gum Patch Spray Inhaler

Men Women Men Women Men Women Men Women Men Women

20–34

5976 10,758 3661 6591 6230 11,217 6008 10,816 2284 4112

35–49

5008 7840 3068 4803 5221 8174 5035 7882 1914 2997

50–64

6637 8309 4066 5090 6920 8663 6673 8354 2537 3176



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Appendix: MethodologyThis report carries on the BMJ Publishing Group’s longstanding tradition of addressingthe health implications of tobacco use. Please see www.bmj.com and www.tobaccocon-trol.bmj.com for other high-quality publications on tobacco use and smoking cessation.For this paper, we have presented the results of a systematic review on the effective-ness of interventions to increase smoking cessation among adults, based on the BMJClinical Evidence search and appraisal methodology described at http://www.clinicalevidence.com/ceweb/about/search_process.jsp. We included the best evi-dence available, focusing on systematic reviews and randomized studies for theeffectiveness of interventions. We excluded trials with self-reported cessation as theseroutinely overestimate biochemically validated cessation. We only included trials with afollow-up of at least 6 months after the start of the intervention. Resuming smokingbefore that time can be considered part of the quit attempt rather than a subsequentrelapse. On the other hand, differences in longer term cessation rates may be diluted bysmokers who have made subsequent quit attempts. We extracted information from trialson the study population, patients’ readiness to quit, and other demographic data. Wespecifically noted trials conducted in specific populations and settings and investigatedwhether interventions were differentially effective for these groups. We did not system-atically search for papers on predictive factors for successful quit attempts, butextracted relevant information from our systematic treatment searches, other importantarticles, and from discussions with our expert panel.

Our approachWe searched MEDLINE, EMBASE, the Cochrane Library, the NHS Centre for Reviewsand Dissemination (CRD), the Database of Abstracts of Reviews of Effects (DARE), theHealth Technology Assessment (HTA), Turning Research into Practice (TRIP), and theNational Institute of Health and Clinical Excellence (NICE) guidance databases forrelevant systematic reviews, randomized controlled trials and other studies throughoutDecember 2006. Some additional searches were carried out in January and February2007.

For the background sections on incidence and prevalence, disease burden of smoking,benefits of cessation, guidelines, legal, policy and economic issues of interventions, wesearched MEDLINE, EMBASE, the National Guideline Clearinghouse, Action onSmoking and Health, and the U.S. Department of Health and Human Services inJanuary and February 2007. We referred to high-quality systematic reviews when theywere available and references recommended by experts. In addition, findings fromreputable, objective sources based on large, controlled surveys or guidelines wereincluded.

After gathering the research, we summarized the studies found and described theconclusions reached by authors of the systematic reviews. Where research was lackingor poor in quality, we reported this. Individual sections were sent to advisors and editorsfor review.

We commissioned two sections, the first one on public policy (written by K. MichaelCummings) and a second on a smoking cessation toolkit for clinicians (written bySherman).

The draft document was sent out to the following panel of expert clinicians for peerreview in June 2007 and the text revised in view of their comments and queries.



+ K. Michael Cummings, PhD, MPH (Chair, Department of Health Behavior,Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute,Buffalo, NY)

+ Carolyn Dresler, MD, MPA (Associate Professor of Health Policy and ManagementDepartment of Health Policy and Management, University of Arkansas for MedicalSciences, Fayetteville, AR)

+ Michael Fisher, MD, MS (Associate Physician in the Division of Pharmacoepidemi-ology and Pharmacoeconomics, Brigham and Women’s Hospital; Instructor in Medicine,Harvard Medical School, Boston, MA)

+ Nancy Lee (Clinical Pharmacist, University of California, UCLA Medical Center, LosAngeles, CA)

+ Maria Leon-Roux, MPH (Tobacco and Cancer Team, Lifestyle, Environment andCancer Group, IARC, WHO, Lyon, France)

+ Nancy Rigotti, MD (Associate Professor, Department of Medicine, Harvard MedicalSchool; Associate Professor, Department of Health and Social Behavior, HarvardSchool of Public Health; Director, Tobacco Research and Treatment Unit, Massachu-setts General Hospital, Boston, MA)

+ Scott Sherman, MD, MPH (Associate Professor, Department of Medicine, NYUMedical Center, NY)

Methodologic challenges of assessing the literature

Appraising studies on treatmentsOur aim, like that of BMJ Clinical Evidence, was to summarize and synthesize evidencefrom high-quality systematic reviews and large well-designed RCTs, and other studieswhen these are not available. Because the health benefits of smoking cessation can bea long time in the future and in most trials the quit rate is low, we have followed atwo-stage process: First providing the evidence on the health benefits of successfulcessation and then summarizing up-to-date, high-quality research on the effectivenessof interventions aimed at achieving cessation.

Disease burden of smokingThe harms of smoking have been repeatedly and convincingly demonstrated in manythousands of studies. However, research is still finding new harms from smoking andquantified estimates of harms will continue to develop as exposures and populationschange and study methods develop.

Using relative risk to measure disease burdenThe relative risk (RR) for a disease does not always give the best measure of thesocietal disease burden of smoking. For example, the RR for smokers for lung cancer isfar higher than that for coronary heart disease (CHD), but the overall disease burdenfrom smoking-related lung cancer and CHD is similar, because of the low baseline riskin never smokers. Age differences are also important, in older age groups the RR fromsmoking for CHD is smaller than for younger people, but because CHD is far morecommon among older people, the smoking-related disease burden is far higher in theelderly. Attempting to ascertain if a residual elevated risk persists after quitting in the



long term is more difficult for conditions with a lower elevated relative risk (e.g., CHD)than for those with a higher one (e.g., lung cancer), even if the smoking-related diseaseburden is similar.

Health benefits from smoking cessation

Which population groups to compareThe effects of smoking cessation are most usefully compared between quitters andcontinuing smokers, because this reflects the real choice that smokers or recent quittersface, rather than risks if they had never smoked.

ConfoundersQuantification of the benefits of cessation mainly rests on the large evidence base fromcohort and case control studies. These have found strong evidence of a reduction inmortality and risk of smoking-related disease following smoking cessation, comparedwith persistent smoking. However, some methodologic problems remain in quantifyingthe size of benefits.

+ Reverse causation: Smokers with symptoms of pre-existing disease, includingundiagnosed disease, tend to be more likely to quit than asymptomatic smokers. Thismeans that higher rates of disease will often be observed among recent quitters thanamong persistent smokers. This effect can have a long term impact for conditions aschronic obstructive pulmonary disease (COPD) and CHD with a long time lag betweenfirst symptoms and morality and can lead to a potentially substantial underestimate ofthe benefits of cessation.

+ Relapse: Another potential cause of bias is that many people who have recentlystopped smoking cessation relapse. This means studies measuring cessation at onlyone point during the study may underestimate the benefits of ongoing cessation.

+ Population trends: A related problem is the reduction in smoking rates seen inmany Western populations over time. This means that many of those initially assessedas smokers will subsequently quit and gain some of the benefits of cessation. Again,studies that assess smoking status only once may underestimate the effect comparedwith studies that assess smoking status at multiple points.

+ Health behavior: However, other unadjusted confounders may lead to overestima-tion of the benefits, as it is likely that people who have quit smoking will display otherhealthy behaviors compared with persistent smokers.

Effectiveness of interventions for smoking cessation

Best available evidenceWe have selected well-conducted systematic reviews and randomized controlled trialsas our primary evidence source as these provide the best evidence of effectiveness fortreatments. Public policy interventions are more difficult to study and are usually basedon interrupted time series data or other observational studies.

How to measure cessationSimply asking people whether they currently smoke will identify a fair number that quitjust a few days previously, and are more likely to relapse. With better questions (e.g.,“Have you smoked any cigarettes in the last 30 days?”) the rate of overreporting can be



held at 5% to 10%, although it is higher in a few special populations, such asadolescents, pregnant smokers, and people enrolled in randomized smoking cessationtrials.143,144

Biochemical measures are used in smoking cessation studies rather than in routineclinical practice.

One of the available biochemical measures is exhaled carbon monoxide (Table 8).Measurements are not specific to cigarettes and half-life is short (3 to 5 hours). Levelsfall to normal in 24 hours.

Table 11. Exhaled carbon monoxide in nonsmokers and smokers145

Smoking intensity Exhaled carbon monoxide (ppm)

Nonsmoker 0–6

Light 7–10

Moderate 10–20

Heavy > 20

Another biochemical marker of smoking is cotinine, the primary metabolite of nicotine,which can be detected in serum, saliva, and urine. It has a long half-life (16 hours) andcan detect smoking in the preceding 3 to 4 days, but requires laboratory analysis.145

Cotinine will generate a false-positive test result in patients using nicotine replacement.

How to assess smoking intensityHeavy, light, and moderate smoking is defined and assessed differently in the includedstudies. We have not prioritized any one method but listed results for subgroups aspresented in each study.

Length of follow-upSmoking cessation is a process rather than a state. Similar to many chronic conditionswhere cure is rare, tobacco use is a relapsing and remitting condition. Even failing quitattempts matter as they reduce exposure to tobacco smoke and may be a predictor offuture success. Most relapses occur within days after quitting which imply treatmentmay need to be most intense early in the process. A lapse, which is smoking one or twocigarettes, is a strong predictor of relapse and implies the need for enhancing thetreatment. Most relapses occur within 3 months of the original quit day, which is whymost treatment programs are focused on the first 12 weeks of the quit process. Thelonger one abstains from cigarettes continuously, the greater the odds of remainingsmoke-free. Follow-up of 1 or 2 years would be more desirable, but with too few studiesproviding such long-term data, in this review we have focused on studies that reportedcessation measure at a minimum of 6 months.



Toolkit: 12-step guide to a primary care systemsapproach for smoking cessation

Goal: To improve tobacco control efforts in medical practiceAll of a health care site’s activities aimed at helping people to quit smoking can begrouped together as tobacco control. This may range from the traditional, but stillunderutilized, physician counseling to environmental tools (posters, pamphlets, etc.) toreminder systems that guide practice. The purpose of this toolkit is to help develop acomprehensive plan to improve tobacco control efforts at your site, ultimately leading tofewer smokers and less subsequent tobacco-related morbidity and mortality.

This toolkit is based on a practice with one or more physicians, along with additionaloffice staff (e.g., clerk, nurse). The main reason why most office-based efforts fail is thatthey rely too much on the physician. To excel at smoking cessation, delegation is key.

Every smoker interested in quitting should receive three things: 1) medications, 2)counseling, and 3) follow-up. The following 12-step approach is aimed at helping toconsistently deliver evidence-based cessation services to each and every smoker.

Step 1: Identify a coordinatorSomeone should be appointed to be in charge of smoking cessation. Make it part ofhis/her duties. Set measurable goals. Determine what rewards (including a financialbonus) the person will receive for success.

Step 2: Create a planThe coordinator should develop a multidimensional plan to improve tobacco controlefforts, which will be further refined in conjunction with the physician(s) and all officestaff. In a multi-physician practice, it may help to identify one physician most responsiblefor smoking cessation to act as a clinical resource for the coordinator.

Step 3: Create a supportive environmentReview the waiting room and all exam rooms. Obtain posters, flyers, and cards thatpromote cessation. If there is a government or other telephone quit line, ensure thatthere are handouts available. Any forms needed by staff (e.g., fax referral forms) shouldbe stocked in every room where they are needed and checked on a regular basis.Consider getting buttons for all staff that say, for example, “Interested in quittingsmoking? Ask me—I can help.”

Step 4: Identify all smokersThis is the second most important step. Treatment cannot be offered to all smokersunless they are identified. Identification should be clear, obvious, and consistent.Common approaches are colored stickers on the outside of charts or a flag in anelectronic medical record.

Step 5: Make smoking status part of checking inIf patients fill out a questionnaire for each visit, ensure that tobacco use is part of it.Along with verifying address and insurance information, clerical staff should verifysmoking status. Current smokers can be given a handout encouraging them to quit(“Ask your doctor . . .”), and any free offers (e.g., free medications through the quit line)should be mentioned.



Step 6: Make smoking assessment and advice a vital signIn most settings, a nurse or health technician sees each patient before the physicianand records vital signs. Adding smoking to the list of vital signs increases cessationrates. Staff can also assess interest in quitting, advise each patient to quit, and describeavailable options.

Step 7: Brief physician advicePatients often identify advice from their physician as a key factor in helping them quit. Inthe interest of efficiency, this should be kept brief—30 to 60 seconds. Advice should beclear, strong, and personalized. With patients interested in quitting (determined in Step6), a physician might say, “It’s great that you’re interested in quitting smoking. As yourdoctor, I think it’s one of the most important things you can do for your health. It willparticularly help you because <tailor to each patient>. I am going to ask _______ to talkto you some more about quitting. Also, I strongly encourage you to let us give you amedication to help you quit, as it doubles your chance of success.”

Step 8: Post-physician adviceA staff member in your office or practice needs to provide additional counseling tosupplement the physician’s brief advice. It need not take long—up to 10 minutes issufficient. In many settings, it will be the nurse providing this advice, but it could be ahealth educator, a pharmacist, or even a clerk. The key tasks are: 1) to set a quit date,2) to coordinate dispensing of smoking cessation medications, and 3) to provide briefcounseling. Many people find it helpful to provide a handout to augment the counseling,although it does not lead to higher quit rates.

Step 9: Record services providedIf at all possible, there should be some way to track what services were provided. Wasthe patient screened by the clerk at check-in? Did the physician provide brief advice?Were medications offered? This can be done in several different ways—with theelectronic medical record, a paper smoking cessation log, or simply a smokingcessation stamp or template on each smoker’s visit note. If the stamp is used, the clerkcould stamp the note initially and then each successive person could check or initial iftheir part was done.

Step 10: MeasureThis is by far the most important step. It is exceedingly difficult to improve ifperformance is not monitored. This is precisely why recording the services provided(Step 9) is important. It does not matter how performance is measured —electronicallyor on paper—as long as it is done. Identify the key processes to be measured. Sometypical ones are: whether each smoker was advised to quit, offered smoking cessationmedications, and offered referral to an available smoking cessation program ortelephone quit line. On a regular basis (e.g., monthly or quarterly), all staff should goover the measured results.

Step 11: Follow-upA staff member from the office should call all smokers in follow-up. An ideal minimum is2 calls. The first should be 1 to 2 weeks after the patient’s quit date (if one was set), toprovide counseling during this most vulnerable period. The second call should be at 6months, to assess smoking status and to offer people who are still smoking anotherchance to quit. It’s important to remember to document the calls and the outcomes.



Step 12: Reward yourselvesSystem redesign is hard work. Looking over the results in Step 10 is very helpful tokeep staff motivated, but financial measures are also important. Everyone can berewarded for good performance. Some ideas include singling out top performers for anextra bonus or having a party to celebrate when you reach a certain number oflong-term (6 months) nonsmokers. Put up posters to celebrate your success and toremind patients of what is available.

Toll-free quit lines

+ National Network of Tobacco Cessation:1–800-QUITNOW (1-800-784-8669) and 1-800-332-8615

+ National Cancer Institute:1-877-44U-QUIT (1-877-448-7848)

Additional resources

+ Centers for Disease Control and Prevention: Smoking & tobacco use (U.S. Depart-ment of Health and Human Services)http://www.cdc.gov/tobacco/

+ MedlinePlus: Smoking cessation (a service of the U.S. National Library of Medicineand the U.S. National Institutes of Health)http://www.nlm.nih.gov/medlineplus/smokingcessation.html

+ National Cancer Institute: Quitting smoking, smoking prevention (U.S. NationalInstitutes of Health)http://www.cancer.gov/cancertopics/smoking/quitting



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