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Tools in the Battle Against Smoking and Tobacco Heart Institute, Hadassah Hospital, Jerusalem, ISRAEL Chaim Lotan, MD 3-C CON, AHMEDABAD, FEBRUARY 2011.

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Presentation on theme: "Tools in the Battle Against Smoking and Tobacco Heart Institute, Hadassah Hospital, Jerusalem, ISRAEL Chaim Lotan, MD 3-C CON, AHMEDABAD, FEBRUARY 2011."— Presentation transcript:


2 Tools in the Battle Against Smoking and Tobacco Heart Institute, Hadassah Hospital, Jerusalem, ISRAEL Chaim Lotan, MD 3-C CON, AHMEDABAD, FEBRUARY 2011

3 Smoking and coronary artery disease History Epidemiology CV Effects Importance of Cessation


5 Cigarette Smoking as a Risk Factor for Cardiovascular Disease was recognized in the results of the Framingham Heart Study in 1960

6 Smoking kills more people each year than  alcohol  cocaine  crack  heroin  homicide  suicide  car accidents  fires  AIDS C O M B I N ED!!!

7 Smoking Cessation: New Concepts of Management to Prevent Hazardous Consequences

8 Smoking and coronary artery disease History Epidemiology CV Effects Importance of Cessation

9 WHO World Health Report.Tobacco Atlas.2008. Global Cigarette Consumption

10 Section 2: The Hazards of Smoking

11  1.25 billion smokers Worldwide  30 million smokers added every year  84% of smokers live in developing countries Africa & Middle East (17% of World’s population) accounts for 7% of World’s total cigarette consumption 8 smokers die every minute Facts & Numbers Voute J, World Heart Foundation

12 Tobacco – a major health problem now and for the future

13 One out of two lifelong adult smokers will die from a smoking related disease. CDC. Projected smoking-related deaths among youth – United States. MMWR 1996;45(44):971-974

14 Gender-specific Smoking Prevalence Across the World 1.Mackay J, Eriksen M. The Tobacco Atlas. Second Ed. American Cancer Society, 2006. 1.25 billion smokers worldwide 1 US24%19% Australia19%16% Belarus53%7% Brazil22%14% Canada22%17% Chile48%37% China67%2% Egypt45%12% France30%21% Iceland25%20% Mexico13%5% Iran22%2% Kenya21%1% Sweden17%18% Philippines41%8% Portugal33%10% South Africa 23%8% India47%17% Russian Federation 60%16% Italy33%17% Spain39%25% Germany37%28% MenWomen

15 4 year-old addict to smoking in Indonesia

16 Smoking and coronary artery disease History Epidemiology CV Effects Importance of Cessation

17 Smoking: Leading Preventable Cause of Disease and Death 1 Cancer Lung (#1) Leukemia (AML, ALL, CLL) 2-4 Oral cavity/pharynx Laryngeal Esophageal Stomach Pancreatic Kidney Bladder Cervical Cardiovascular Ischemic heart disease (#2) Stroke – vascular dementia 5 Peripheral vascular disease 6 Abdominal aortic aneurysm Respiratory COPD (#3) Pneumonia Poor asthma control Reproductive Low-birth weight Pregnancy complications Reduced fertility SIDS Other Adverse surgical outcomes/wound healing Hip fractures Low-bone density Cataract Peptic ulcer disease in Helicobacter pylori-positive patients AML = acute myeloid leukemia; ALL = acute lymphocytic leukemia; CLL = chronic lymphocytic leukemia; COPD = chronic obstructive pulmonary disease; SIDS = sudden infant death syndrome. Surgeon General’s Report. The Health Consequences of Smoking; 2004. Sandler DP, et al. J Natl Cancer Inst. 1993;85:1994-2003. Crane MM, et al. Cancer Epidemiol Biomarkers Prev. 1996;5:639-644. Miligi L, et al. Am J Ind Med. 1999;36:60-69. Roman GC. Cerebrovasc Dis. 2005;20:91-100. Willigendael EM, et al. J Vasc Surg. 2004;40:1158-1165.

18 The INTERHEART Study Published 2004 Finding: Nine potentially modifiable risk factors are strongly associated with AMI worldwide

19 INTERHEART: Smoking and MI 2 4 8 16 OR (99% CI) 0 1-5 6-10 11-15 16-20 21-25 26-30 31-40 >40 #cigarettes smoked per day Odds of myocardial infarction

20 Risk of AMI associated with Risk Factors in the Overall Population Risk FactorControls %Cases %Odds ratioPAR(99%)CI ApoB/ApoA1(5vs1) ± 0.5541. ± 4.5 Current smoking 26.7645.15 2.95 ± 0.2 C+Former smoking 48.1265.19 2.27 ± 0.436.4 ± 2.6 Diabetes7.5218.453.08 ± 0.312.3 ± 0.8 Hypertension21.9139.022.48 ± 0.223.4 ± 1.7 Abd obesity (3vs1)33.3246.312.24 ± 0.233.7 ± 3.6 All psychosocial--2.51 ± 0.428.8 ± 6.8 Veg&fruit daily42.3635.790.70 ± 0.112.9 ± 3.7 Exercise19.2814.270.72 ± 0.125.5 ± 5.4 Alcohol intake24.4524.010.79 ± 0.113.9 ± 4.6 COMBINED129.20 (90-185)90.4 ± 2.3

21 Cardiovascular Risk Factors Smoking > 1 ppd Weight > 129% ideal vs < 112% Cholesterol > 268 vs < 219 Systolic BP > 150 vs < 130 Diastolic BP > 94 vs < 80 Relative Risk of Major Coronary Events 8422 Men Age 40-64 Followed for 72,011 person-years The Pooling Project Research Group. J Chron Dis 1978;31:201-306. There are also interactions between risk factors.

22 Causes Related to Smoking WHO top ten causes of death 3  1 in 10 adult deaths are smoking-related 2  500,000,000 people alive today will die from smoking-related causes 2 1. Surgeon General’s Report, 2004. 2. World Bank, 1999. 3. World Health Organization, 2003. Smoking Is Related To 5 of the Top 10 Leading Causes of Death Worldwide 1

23 Platelet function Coagulation (PAI-1) Inflammation (hs-CRP, cytokine, chemokine) Smooth muscle cells LDL-C HDL-C TG Viscosity Endothelial function Collagen Macrophages MMPs How does smoking induce ACS ?


25 Pais P, Fay MP, Yusuf S Indian Heart J 2001; 53:731-5 N=300 AMI, 300 Controls Role of AMI due to tobacco in India


27 Intl J Epidemiol 2005;43(6):1395-1402 Tobacco associated mortality in Mumbai (Bombay) India. Results of the Bombay Cohort Study Gupta PC, Pednekar MS, Parkin DM, Sankaranarayanan R Background Little is known about the excess mortality from forms of tobacco use other than cigarette smoking that are widely prevalent in India, such as bidi smoking and the various forms of smokeless tobacco use. We report on absolute and relative risks of mortality among various kinds of ever tobacco users vs never-users in the city of Mumbai, India. (n=99570) Results The adjusted relative risk was 1.37 (95% CI 1.23–1.53) for (men) cigarette smokers and 1.64 (95% CI 1.47–1.81) for bidi smokers, with a significant dose– response relationship for number of bidis or cigarettes smoked. Women were essentially smokeless tobacco users; the adjusted relative risk was 1.25 (95% CI 1.15– 1.35). Conclusions Bidi is no less hazardous than cigarette smoking, and smokeless tobacco use may also result in significantly increased mortality.

28 Smokeless tobacco and health in India and South Asia Prakash C. GUPTA, Cecily S. RAY Abstract: South Asia is a major producer and net exporter of tobacco. Over one-third of tobacco consumed regionally is smokeless. Traditional forms like betel quid, tobacco with lime and tobacco tooth powder are commonly used and the use of new products is increasing, not only among men but also among children, teenagers, women of reproductive age, medical and dental students and in the South Asian diaspora. Smokeless tobacco users studied prospectively in India had age-adjusted relative risks for premature mortality of 1.2–1.96 (men) and 1.3 (women). Current male chewers of betel quid with tobacco in case-control studies in India had relative risks of oral cancer varying between 1.8–5.8 and relative risks for oesophageal cancer of 2.1–3.2. Oral submucous fibrosis is increasing due to the use of processed areca nut products, many containing tobacco. Pregnant women in India who used smokeless tobacco have a threefold increased risk of stillbirth and a two- to threefold increased risk of having a low birthweight infant. In recent years, several states in India have banned the sale, manufacture and storage of gutka, a smokeless tobacco product containing areca nut. In May 2003 in India, the Tobacco Products Bill 2001 was enacted to regulate the promotion and sale of all tobacco products. In two large-scale educational interventions in India, sizable proportions of tobacco users quit during 5– 10 years of follow-up and incidence rates of oral leukoplakia measured in one study fell in the intervention cohort. Tobacco education must be imparted through schools, existing government health programmes and hospital outreach programmes. Respirology 2003;8(4):419-31

29  Tobacco consumption is a major source of mortality and morbidity in India.  Studies have shown contradictory results regarding smokeless tobacco use as a cardiovascular risk factor, but many show conclusive connection.  2003 Study of adults males in a rural village in Haryana, northern India (chosen randomly)

30 Prevalence of tobacco use in study population (N=443):  Non-user of tobacco26.6%  Smokeless tobacco user (exclusive) 21%  Smoker of tobacco (exclusive) 33%  Both smoker and smokeless tobacco user 19.4% Pandey A etal. Tobacco Induced Diseases 2009; 5:15 Exclusive ST User N=93 (21%) Non User of tobacco N=118 (26.6%) P value Mean body weight (kg) 51.8 ±10.453.2 ±12.50.386 Family history of HTN 5.4% (n=5)6.77% (n=8)0.779 Regular exercise 12.9% (n=12)11.8% (n=14)0.835 Mean systolic BP (mmHg) 139.2 ±17.4135.7 ±18.80.16 Mean diastolic BP (mmHg) 86.8 ±11.582.6 ±11.50.01 Systolic HTN prevalence 43% (n=40)36.4% (n=43)0.39 Diastolic HTN prevalence 40.9% (n=38)22.9% (n=27)0.0018 Conclusion: Smokeless tobacco consumption is associated in this population with increased prevalence of high blood pressure, which is an indicator of increased disposition to major adverse cardiac events.

31  With smoke-free laws, smokeless tobacco (ST) products are being marketed as smoking substitutes: snuff, chewing tobacco, spitless pouched moist snuff, compressed tobacco lozenges.  A recent US study found no reduction in smoking rates among people using ST as replacement, although a previous (2006) Swedish study showed an overall country reduction in smoking with increased overall ST consumption. smokeless tobacco

32 Global Common Smokeless Tobacco Products North America Chewing tobacco: loose leaf, plug, twist, iq’mik Snuff (spit tobacco): moist, dry Snus (drier moist snuff) Oral compressed tobacco lozenges South AmericaChimo, tobacco with NaHCO 3, brown sugar, vanilla SwedenSnus (finely ground moist tobacco) BritainGutka (betal quid with tobacco, betel nut and slaked lime), snuff Central Asia Gul (tobacco powder and molasses), nass or naswar, niswar, pan masala or betel quid, zarda East/SE AsiaGutka, pan masala or betel quid South Asia Snuff (creamy), gul, gutka, khaini, mawa, mishri, misheri, qiwam or kima, red tooth powder, snus, snuff Middle EastNass or naswar, niswar, shammah, zard SudanToombak (fermented ground powdered tobacco with NaHCO 3

33 Chemical Composition of ST Products  Similar to cigarettes, nicotine is the principal alkaloid  Amount of total and free nicotine varies substantially - generally, concentration similar in oral snuff and cigarette tobacco, somewhat lower in chewing tobacco  Minor alkaloids: nornicotine, anatabine, anabasine  Carcinogens: Combustion-derived Benzo[a]pyrene and other polycyclics lower than in cigarette smoking  Carcinogens: Nitrosamines - highest known nonoccupational exposure  Nitrite, nitrate, formate, chloride, sulfate, phosphate

34 Impact of Smokeless Tobacco Products on Cardiovascular Disease: Implications for Policy, Prevention and Treatment: A Policy Statement From The American Heart Association  Long-term use of smokeless tobacco products increases the odds of fatal heart attack or fatal stroke (according to analysis of several studies).  The AHA advises against smokeless tobacco products for smoking cessation - they are not a “safe” alternative to smoking, and carry the risk of addiction and return to smoking. 2010

35 Second-Hand Smoke ( Environmental Tobacco Smoke “ETS” – Passive Smoking)  Secondhand smoke is a mixture of thesmoke given off by the burning endof acigarette, pipe or cigar and thesmoke exhaled from the lungs of smokers.  Secondhand smoke is a mixture of the smoke given off by the burning end of a cigarette, pipe or cigar and the smoke exhaled from the lungs of smokers.  It is involuntarily inhaled by nonsmokers, lingers in the air hours after cigarettes have been extinguished and can cause or exacerbate a wide range of adverse healthncluding Cardiovascular cancer,respiratory infectionsandasthma.  It is involuntarily inhaled by nonsmokers, lingers in the air hours after cigarettes have been extinguished and can cause or exacerbate a wide range of adverse health effects, including Cardiovascular cancer, respiratory infections, and asthma. California Environmental Protection Agency. Identification of Environmental Tobacco Smoke as a Toxic Air Contaminant. Executive Summary. June 2005.

36 The Effects of Second-Hand Smoke Short-term effects of second-hand smoke:  Coughing  Headache  Eye irritation  Sore throat  Sneezing and runny nose  Feeling sick asthma attack  Breathing problems (and possibly an asthma attack)  Irregular heartbeat (a particular problem for people with heart disease) Long-term effects of second-hand smoke: asthma, hay fever,  Worsening of chest problems and allergies like asthma, hay fever, bronchitis and emphysema bronchitis and emphysema  Increased risk of heart disease lung cancer  Increased risk of lung cancer  Pregnant women exposed to second hand smoke can pass on the harmful gases and chemicals onto their babies.

37 The health consequences of smoking and second hand smoke evolve over a lifetime. Pregnancy Infant health Adolescence Adulthood Child Health and Smoking Fetal growth Birth weight Abortions Premature Birth Fetal Death SIDS Physical Growth Behavior and cognitive development Respiratory infections More hospitalization Small airway dysfunction Cough Wheezing Phlegm production other respiratory symptoms Chronic bronchitis Emphysema Lung cancer by 20%–30% Coronary heart disease Stroke COPD 1.News release, June 27, 2006; US Department of Health & Human Services. Available at: 2.Mackay J, et al. The Tobacco Atlas. World Health Organization, 2006. 3.Teo KK, et al. Lancet. 2006;368:647-658. 4.Fagerström K. Drugs. 2002;62:1-9. 5.Blizzard L, et al. Arch Pediatr Adolesc Med. 2004;158:687-693. 6.Leung GM, et al. Arch Pediatr Adolesc Med. 2004;158:687-693.

38 Passive Smoking and CV Disability CV disability & mortality  Have a clear relationship to CV disability & mortality  ~ 37,000 to 40,000 people die from cardiovascular disease caused by other people’s smoke every year 35,000 non-smokers die from coronary heart disease.  ~ 37,000 to 40,000 people die from cardiovascular disease caused by other people’s smoke every year. Of these, 35,000 non-smokers die from coronary heart disease. American Heart Association 2007

39 Importance of Not Smoking During Pregnancy Rate of Infants with Low-Birth Weight* in Taiwanese Infants by Smoking Status of the Mother (N=9499) * Low birth weight defined as <2500 g † ORs of having low birth weight infants, adjusted for mothers’ age, education level, parity, and alcohol consumption level, as well as the sex of the infants ‡ Before or during first trimester. Abbreviations: CI, confidence interval; OR, odds ratio 1.Wen CP, et al. Tob Control. 2005;14(Suppl 1):i56-i61. OR 1.1 (95% CI: 0.9–1.4) OR 1.7 (95% CI: 1.0–2.8)

40 Second hand Smoke

41 Smoking and coronary artery disease History Epidemiology CV Effects Importance of Cessation

42 Why Quit? Potential Health Benefits of Quitting Smoking Cessation 3 months Lung function may start to improve with decreased cough, sinus congestion, fatigue, and shortness of breath Cardiovascular Heart Disease (CHD): excess risk is reduced by 50% among ex-smokers 1 year Stroke risk returns to the level of people who have never smoked at 5–15 years post-cessation 5 years Lung cancer risk is 30%–50% that of continuing smokers 10 years CHD risk is similar to never smokers 15 years 1.USDHHS. The Health Benefits of Smoking Cessation: A Report of the Surgeon General, 1990. Available at: 2.American Cancer Society. Guide to Quitting Smoking. Available at:

43 Quitting at Any Age May Increase Life Expectancy Age Stopped Smoking: 45–54 Years Old Age (Years) Results From a Study of Male Physician Smokers in the UK Age Stopped: 45–54 Nonsmokers Cigarette Smokers Percentage Survival from Age 50  Even quitting smoking later in life can lead to longer life expectancy 1.Doll R, et al. BMJ. 2004;328:1519-1527.


45 Smoking bans in public places and workplaces are significantly associated with a reduction in AMI incidence, particularly if enforced over several years.

46 Countries Banning Smoking in Public Places  Albania 2007  Andorra (partial)  Argentina-Buenos Aires 2006  Armenia (partial)  Australia 2007-10  Austria (partial)  Bahrain 2008  Bosnia-Herzegv.2007  Brazil 2009  Bulgaria (partial)  Canada  Chile (partial)  China (partial)  Colombia 2009  Croatia 2008-9  Cyprus 2009  Czech Rep.(partial)  Denmark 2007  Estonia (partial)  Finland 2007  France 2008  Germany (contested)  Greece 1010  Guatemala  Hong Kong 2007  Hungary (partial)  Iceland  India (partial)  Indonesia (partial)  Ireland 2004  Israel  Kazakhstan 2003-9  Kenya 2007  Latvia 2010  Lithuania (partial)  Luxemburg (partial)  Macedonia 2010  Malta  Malaysia  Mexico 2008  Monaco (partial)  Montenegro  Morocco  Mozambique 2007  Namibia 2010  Netherlands  New Zealand 2004  Nigeria  Norway 2004  Paraguay  Peru  Philippines (partial)  Poland (partial)  Portugal 2007  Puerto Rico  Singapore  Serbia  Slovenia  South Africa 2001  Spain 2006-10  Sweden (partial)  Syria 2009  Thailand 2008 and more! Source: Wikipedia

47 Beneficial Effects of Smoking Ban for Employees Eisner M et coll., JAMA 1998, 280, 1909-1914 Number of barmen with symptoms Source: 10 20 30 40 Before ban After Ban 0 Symptoms among 67 barmen before and after ban dyspnea morning cough cough sputum eye irritation nose irritation throat irritation

48 Smoking and coronary artery disease History Epidemiology CV Effects Importance of Cessation Nicotine addiction

49 Nicotine Addictive or Just a Bad Habit??????

50 WHAT IS ADDICTION? ”Compulsive drug use, without medical purpose, in the face of negative consequences” Alan I. Leshner, Ph.D. Former Director, National Institute on Drug Abuse National Institutes of Health


52 NICOTINE PHARMACODYNAMICS Nicotine binds to receptors in the brain and other sites in the body. Other: Neuromuscular junction Sensory receptors Other organs Central nervous system Exocrine glands Adrenal medulla Peripheral nervous system Gastrointestinal system Cardiovascular system Nicotine has predominantly stimulant effects.

53 Mechanism of Action of Nicotine in the Central Nervous System  Nicotine binds preferentially to nAChRs in the central nervous system; one key area is the α4β2 nicotinic receptor in the VTA  After nicotine binds to the α4β2 nAChR in the VTA, dopamine is released in the nAcc which is believed to be linked to reward 44 22 22 22 44  4  2 nicotinic acetylcholine receptor (nAChR)

54 The Cycle of Nicotine Addiction  Nicotine binding causes an increase in release of dopamine 1,2  Dopamine gives feelings of pleasure and calmness 1  competitive binding of nicotine to nicotinic acetylcholine receptors causes prolonged activation, desensitization, and upregulation 2 1.Jarvis MJ. BMJ. 2004; 328:277-279. 2.Picciotto MR, et al. Nicotine and Tob Res. 1999:Suppl 2:S121-S125. Dopamine Nicotine

55 The Cycle of Nicotine Addiction ( continued)  As nicotine levels decrease, receptors revert to an open state causing hyperexcitability leading to cravings 1,2  The dopamine decrease between cigarettes leads to withdrawal symptoms of irritability and stress 1  The smoker craves nicotine to release more dopamine to restore pleasure and calmness 1 1.Jarvis MJ. BMJ. 2004; 328:277-279. 2.Picciotto MR, et al. Nicotine and Tob Res. 1999:Suppl 2:S121-S125. Dopamine Nicotine

56 Withdrawal Syndrome: A Combination of Physical and Psychological Conditions, Making Smoking Hard to Treat Restlessness or impatience Increased appetite or weight gain Anxiety (may increase or decrease with quitting) Dysphoric or depressed mood Irritability, frustration, or anger Difficulty concentrating Insomnia/sleep disturbance 1. DSM-IV-TR. APA; 2006: Available at: Decreased heart rate

57 The greatest risk of relapse is during the first three months after quitting. 37% have their first lapse between 8:00pm and midnight 50% are likely to relapse in the first month 67% are likely to relapse in the first three months DSM-IV-TR. APA; 2006: Available at:

58 “Nine out of ten ex-smokers who have a cigarette after quitting later return to smoking” (Brandon, 1990)

59 Many Health Organizations Emphasise the Important Role Physicians Can Play in Helping Their Patients Quit Smoking 1.World Health Organization. Mayo report on addressing the worldwide tobacco epidemic through effective, evidence-based treatment. Report of an expert meeting, March 1999, Rochester (Minnesota) USA. Available at: Accessed July 2006. 2.American Cancer Society. Tobacco control strategy planning, companion guide #2: Engaging doctors in tobacco control. Available at: 3.The American Academy of Family Physicians. Tobacco use, prevention and cessation. Available at: 4.National Institute for Health and Clinical Excellence. Brief interventions and referral for smoking cessation in primary care and other settings. Available at:  World Health Organization 1  Health Professionals Against Smoking 2  The American Academy of Family Physicians 3  American Medical Association 2  National Institute for Health and Clinical Excellence 4

60 ASK about tobacco USE ADVISE tobacco users to QUIT ASSESS READINESS to make a quit attempt ASSIST with the QUIT ATTEMPT ARRANGE FOLLOW-UP care US PHS Guideline – Treating Tobacco Use and Dependence: 2008 Update Tobacco Dependence Support – The “5 A’s”


62 US PHS Guideline – Treating Tobacco Use and Dependence: 2008 Update First-line Pharmacotherapies for Tobacco Dependence 1 Nicotine replacement therapy (NRT) Patch Gum Inhaler Nasal spray Sublingual tablets/lozenges Bupropion SR Champix (Varenicline) 1.Fiore MC, et al. Clinical Practice Guideline. Treating Tobacco Use and Dependence: 2008 Update. USDHHS. PHS. Rockville, MD. 2008.  All decrease cravings, withdrawal  20-25% quit rates at 1 year

63 21

64 (varenicline) A Selective  4  2 Nicotinic Acetylcholine Receptor Partial Agonist

65 Binding of nicotine at the  4  2 nicotinic receptor in the Ventral Tegmental Area (VTA) is believed to cause large amounts of dopamine to be released at the Nucleus Accumbens (nAcc) Champix  (varenicline): A Highly Selective  4  2 Receptor Partial Agonist Nicotine 1. Coe JW et al. Presented at the 11th Annual Meeting and 7th European Conference of the Society for Research on Nicotine and Tobacco. 2005. Prague, Czech Republic. 2. Picciotto MR et al. Nicotine Tob Res. 1999; Suppl 2:S121-125. Varenicline Binding of nicotine at the  4  2 nicotinic receptor in the Ventral Tegmental Area (VTA) is believed to cause release of dopamine at the Nucleus Accumbens (nAcc) Varenicline is an  4  2 nicotinic receptor partial agonist, a compound with dual agonist and antagonist activities. This is believed to result in both a lesser amount of dopamine release from the VTA at the nAcc as well as the prevention of nicotine binding at the  4  2 receptors

66 Champix  (varenicline) Efficacy Measurements: CO-Confirmed 4-Wk Continuous Abstinence Rates Wks 9– 12 Gonzales et al.Jorenby et al. VareniclineBupropion SRPlacebo 100 44.0 43.9 29.8 29.5 17.617.7 0 20 40 60 n=352n=329n=344 n=342n=341 1. Gonzalez D et al. JAMA. 2006;296:47-55. 2. Jorenby DE et al. JAMA. 2006;296:56-63. The 9-12 week Continuous Abstinence Rate is defined as the percentage of subjects who abstained from smoking (not even a puff) from Week 9 through 12 of the study as confirmed by both subject self-report and by end-expiratory carbon monoxide (CO) measurement P < 0.001 Continuous Abstinence Rate (%) P = 0.001

67 Smoking is Cool….again


69 Prevention of smoking


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