1. The essentials of smoking cessation
Dr Alex Bobak
GP and GPSI in Smoking Cessation Wandsworth, London
Speaker’s note:
The speaker notes are for guidance only, they are intended to be used as an adjunct to the slides. They provide extra information to clarify or expand on the points made on the slides.
Presenters are encouraged to become familiar with the information but naturally may wish to choose their own form of wording to articulate the points.
It is expected that the majority of the core slides (slides 1-48) should be used in a presentation to a GP audience. Any additional slides from the supplementary section (slides 49 onwards) may be added in as appropriate depending on the audience and time allowed.
The case histories are intended to stimulate some audience discussion; some discussion points have been proposed, but you or your audience may interpret the clinical aspects differently.
The slide set is divided into the following sections:
Burden of smoking and benefits of quitting
Pharmacotherapy in smoking cessation
The role of primary care in smoking cessation
Case studies
Supplementary slides
includes additional NRT and bupropion information.

2. Smoking: the size of the problem
Smoking is the largest preventable cause of disease and premature death in the world1
More than 50% of long-term smokers die prematurely due to smoking-related diseases2
1. WHO Report on the Global Tobacco Epidemic: the MPOWER package. Geneva, World Health Organization, 2008
2. Doll R, et al. Br Med J 2004;328:1519–27

3. Smoking is by far the biggest single preventable cause of death and disease in the UK

4. More than 50% of long term smokers die prematurely of smoking related diseases

5. Smoking - the Size of the Problem
13 million adults smoke in the UK
HALF of young adults become long term smokers
Smoking kills HALF of long term smokers

6. What’s in a cigarette?
Nicotine
Tar
Arsenic
Ammonia
Toluene
Phenol
DDT
Cigarette smoke contains more than 4,000 chemicals, including nicotine, carbon monoxide, tar, cadmium, hydrogen cyanide and arsenic.1
The burning of tobacco generates more than 9 billion tar particles per cubic centimetre, constituting the visible portion of cigarette smoke.1
Smokers efficiently extract almost 90% of the particulate as well as gaseous constituents from the smoke.1
It is the nicotine that smokers become addicted to, but the 4,000 or more other chemicals that lead to smoking-related diseases.1
Nitrosamine
Butane
Naphthalene
Carbon monoxide
Hydrogen Cyanide
Cadmium
Cigarette smoke contains more than 4,000 chemicals, including over 60 known carcinogens and metabolic poisons
Ginzel KH. What’s in a cigarette?
1. Ginzel KH. What’s in a cigarette?

7. Why do people keep smoking?
NICOTINE
ADDICTION
HABIT
SOCIAL

8. The power of nicotine addiction
60% smoke again post MI (40% within 2 days)
50% smoke again post laryngectomy
50% smoke again post pneumonectomy
80% of women do not stop smoking during pregnancy
Nicotine addiction is extremely powerful and makes quitting smoking very difficult.
The following startling statistics highlight the power of nicotine addiction:
nearly 38% of smokers who suffer a heart attack return to smoking while still hospitalized.1
40% of those who have had a laryngectomy try smoking again soon afterwards2
nearly 50% of lung cancer patients resume smoking within a year of surgery (pnemonectomy)3
and
only 1 in 4 women who smoke succeed in stopping at some time during pregnancy, and two-thirds of these restart again after the birth of their baby.4
Other indicators of dependence include time from waking to first cigarette. Among smokers of all ages, 15% light up within 15 minutes of waking and nearly half within the first half hour.5
Over 80% of those who smoke more than 20 cigarettes per day say they would find it difficult to go a whole day without smoking.5
Bigelow GE, Rand CS, Gross J, Barling TA, Gotlieb SH. Smoking cessation and relapse among cardiac patients. In: Tims FM, Leubefeld CG (eds). Relapse and recovery in drug abuse. 1986; NIDA Research Monograph. Rockville, MD: US Department of Health & Human Services, Public Health Service, Alcohol, Drug Abuse, and Mental health Administration, National Institute on Drug Abuse.
Himbury S, West R. Smoking habits after laryngectomy. Br Med J 1984; 291:
Davison G, Duffy M. Smoking habits of long-term survivors of surgery for lung cancer. Thorax 1982; 37:
Action on Smoking and Health. Fact sheet No. 7. Smoking, sex and reproduction. May 2004.
Living in Britain General Household Survey Office for National Statistics, Social Survey Division. London: The Stationery Office, 2003.
1. Bigelow GE et al. US DHHS Himbury S Br Med J Davidson G et al. Thorax ASH May 2004.

9. Mechanics of nicotine addiction

10. α4β2 Nicotinic Receptor Nicotine Dopamine Nucleus Accumbens (NAcc)
Ventral Tegmental Area (VTA)
NIC
NIC
Nicotine
Dopamine

11. The dopamine triggered by inhaled nicotine rapidly gets reabsorbed which leads to…..
low mood and craving
which leads to…..

12. Regular smoking leads to a 300% increase in brain nicotine receptors

13. On stopping smoking:
It takes hours for nicotine to leave the body
It takes 8-12 weeks for the nicotine receptors to down-regulate

14. Smokers want to stop ~2–3% succeed in stopping each year3 All smokers
~70%
want to stop1
~2–3%
succeed in
stopping
each year3
~30%
try each year2
About two thirds of smokers in the UK (70%) say they want to stop.1 Nearly 80% have attempted to stop at least once,2 with about 30% actively trying each year.3
Cessation rates increase with age, starting at about 2% per year among smokers in their 20s and 30s, rising to about 4% per year among smokers in their late 40s and 50s.4 Overall, 2% to 3% of all smokers manage to stop permanently each year.5
The percentages shown on the slide mean that, of the current 13 million adult smokers in the UK, about 9 million want to stop and about 4 million will actually try each year with only about 300,000 succeeding in giving up for good.
Many smokers require multiple attempts before succeeding.5,6
Even people with potentially life-threatening smoking-related diseases continue to smoke: 40% of those who have had a laryngectomy try smoking again soon afterwards;7 nearly 50% of lung cancer patients resume smoking within a year of surgery;8 and 38% of smokers who suffer a heart attack return to smoking while still hospitalized.9
1. Bridgwood et al, General Household Survey West, Getting serious about stopping smoking Arnsten, Prim Psychiatry 1996.
1. Bridgwood A, Lilly R, Thomas M et al. Living in Britain: Results from the 1998 General Household Survey. Office for National Statistics, Social Survey Division. London: The Stationery Office, 2000.
2. Hansbro J, Bridgwood A, Morgan A, Hickman M. Health in England 1996: what people know, what people think, what people do. A survey of adults aged in England. Office for National Statistics, Social Survey Division on behalf of the Health Education Authority. London: The Stationery Office, 1996.
3. West R. Getting serious about stopping smoking. A review of products, services and techniques. A report for No Smoking Day, 1997.
4. Stapleton J. Stat Methods Med Res 1998; 7:
5. Arnsten JH. Prim Psychiatry 1996; 3:
6. Rose JE. Ann Rev Med 1996; 47:
7. Himbury S, West R. Br Med J 1985; 291:
8. Davison G, Duffy M. Thorax 1982; 37:
9. Bigelow GE, Rand CS, Gross J et al. Smoking cessation and relapse among cardiac patients. In: Relapse and recovery in drug abuse. NIDA Research Monograph 72. Rockville, Maryland: US Department of Health & Human Services 1986: 167–71.

15. Stopping smoking: What works, what doesn’t

16. A number of tools to aid smoking cessation are available
Non-pharmacological
methods
Counselling
Lifestyle changes
(e.g. increased
exercise)
Pharmacological
methods
NRT
Bupropion SR
Varenicline
Combination of both methods?
NRT = nicotine replacement therapy; SR = sustained release

17. Long term cessation rates
No Pharmacotherapy
Pharmacotherapy
(eg NRT)
Willpower alone
2-3%
4-6%
Support (trained adviser)
10-15%
20-30%

18. Nicotine replacement therapy

19. Nicotine replacement therapy
Available in six different forms
Based on nicotine weaning1
Significantly reduces withdrawal symptoms and cravings vs placebo2
Significantly increases smoking cessation rate vs placebo (odds ratio = 1.77)3
Treatment lasts 8–12 weeks with gradual withdrawal
1. Thompson GH, et al. Ann Pharmacother 1998;32:1067–75
2. Henningfield JE, N Engl J Med 1995;333:1196– Silagy C, et al. Cochrane Database Syst Rev CD000146
CNS = central nervous system

20. NRT-Dosage and use Gum upto 15 or 25/day 2mg or 4mg
Patch 16 or 24 hours strengths
S/L tabs upto 40/day mg
Lozenges min 9 max 15/day mg or 4mg
Inhalator cartridges/day
Spray upto 64 sprays/day

21. Plasma nicotine levels – contrast between cigarettes and NRT25 20 15 10 5
Cigarette
Spray
Plasma nicotine (ng/ml)
Gum/Inhalator/Tablet/lozenge
The cigarette is “a wonderfully efficient nicotine delivery device, delivering the optimum dose of nicotine, rapidly, to the dependent brain”.1
NRT products give lower peak plasma concentrations of nicotine at a slower pace, and as a result lack the rapid onset of pharmacological action achieved with a cigarette.2,3
As the slide shows, NRT products provide plasma nicotine levels of about a third to a half those achieved by cigarette smoking.2
Patch 10 20 30 40 50 60
Time (minutes)
Adapted from: Tobacco Advisory Group of the Royal College of Physicians 2000.
1. Moxham J. Br Med J 2000; 320:
2. Royal College of Physicians of London. Nicotine addiction in Britain: A Report of the Tobacco Advisory Group of the Royal College of Physicians. London: Royal College of Physicians, 2000.
3. Benowitz NL. Drugs 1993; 45:

22. Considerations for patients using NRT
USE ENOUGH! Avoid under-dosing and irregular use.
LONG ENOUGH! Don’t stop early, continue 8-12 weeks.
NOT A PUFF! Slower and less efficient source of nicotine than cigarettes so can not compete.
While NRT is effective in some patients, there are some considerations to its use.
Smokers’ use of NRT is variable.
For example, there is a tendency to under-dosing or irregular usage1,2 while some patients may smoke cigarettes concurrently despite instructions not to.1
Other patients may discontinue treatment prematurely3 or continue to use it long-term.3-6
In general, NRT products are a slower and less efficient source of nicotine compared with inhalation of cigarette smoke.2,3
In addition, some smokers worry that they will transfer their dependence from cigarettes to NRT.7,8 Indeed, there is some evidence suggesting that this might occur with certain presentations.5,9-11
Finally, NRT is not suitable for all patients.12
1. Fant RV, Owen LL, Henningfield JE. Primary Care Clin Office Pract 1999; 26:
2. Rennard SI, Daughton DM. J Resp Dis 1998; 19 (Suppl 8): S20-25.
3. Benowitz NL. Drugs 1993; 45:
4. Hajek P, Jackson P, Belcher M. J Am Med Assoc 1988; 260:
5. Sutherland G, Stapleton JA, Russell MAH et al. Lancet 1992; 340:
6. Hjalmarson A, Franzon M, Westin A, Wiklund O. Arch Intern Med 1994; 154:
7. Anon. Nicotine replacement to aid smoking cessation. Drug Therap Bull 1999; 37:
8. Hughes JR. J Drug Dev 1994; 6:
9. Hughes JR. Biomed Pharmacother 1989; 43:
10. Hughes JR, Hatsukami DK, Skoog KP. J Am Med Assoc 1986; 255:
11. West R, Russell MAH. Psychol Med 1985; 15:
12. Thompson GH, Hunter DA. Ann Pharmacother 1998; 32:

23. Bupropion (Zyban)

24. Bupropion SR
Non-nicotine prescription tablet originally developed to treat depression1
Modifies dopamine levels and noradrenergic activity1
Significantly increases smoking cessation rate vs placebo (odds ratio = 1.94)2
1.Bupropion (Zyban) prescribing information. Available at 2.Hughes et al. Cochrane Database Syst Rev CD000031

25. Bupropion treatment regime
150 mg o.d.
for 6 days
150 mg b.d.
for remainder of 120 tablet treatment course
Start treatment while patient is still smoking and set a ‘target stop date’ in the second week, e.g. day 11 or earlier if the patient feels ready to stop. This is to allow time for plasma levels of bupropion HCI SR to reach steady state and for the drug to start working effectively.1
To help break the cycle of nicotine addiction, bupropion HCl SR should be prescribed and taken as a full 120 tablet treatment course.
If at 7 weeks no effect is seen, treatment should be discontinued.1
A success rate of almost 1 in 3 smokers abstinent at 1 year has been achieved when patients receive the full treatment course of bupropion HCl SR.2
Some patients who succeeded in stopping smoking by the end of treatment were still smoking mid-way through the treatment course.3,4
Previously, it was recommended that bupropion HCI SR be taken at a dose of 150 mg o.d. for 3 days and 150 mg b.d. for the remainder of the treatment course. The SmPC now recommends that bupropion HCI SR is taken at a dose of 150 mg o.d. for 6 days and 150 mg b.d. for the remainder of the treatment course. By allowing a longer period at a lower dose patients will have more time to adjust to their medication.
Patients should choose a quit date in the second week, for example day 11, or earlier if the patient feels ready to stop
1. Zyban 150 mg prolonged release tablets (bupropion HCI) Summary of Product Characteristics, May 2001.
2. Jorenby DE, Leischow SJ, Nides MA et al. N Engl J Med 1999; 340: 685–91.
3. Jamerson BD, Jorenby D, Johnson JA et al. ASAM, November 1998 (Abstract I5A).
4. GlaxoSmithKline, data on file (study 405).

26. Adverse events on bupropion in smokers with CVD. McRobbie 2001
Placebo 25 24 20 18 15 13 12 11 11 10 10 6 5
Insomnia
Headache
Dry mouth
Nausea

27. General population bupropion trial: continuous abstinence rates (%)
Tonstad
et al (2001) 46 23 32 18 25 13 21 11 5 10 15 20 30 35 40 45 50
4-7 wks
4-12 wks
4-26 wks
4-52 wks
Zyban
Placebo
p<0.001)

28. NICE Guidance on NRT & Bupropion
April 2002

29. “Both bupropion and NRT are considered to be among the most cost effective of all healthcare interventions.”
“Estimates of cost-effectiveness……are below £2000 per Life Year Gained”
NICE April 2002

30. Cost Per Life Year Gained
£14,000
£12,000
£10,000
£11,8001
£8,000
Cost per Life Year Saved
£6,000
£4,000
£2,000
Smoking cessation is one of the most cost-effective healthcare interventions that can be made in the NHS today.1,2
Indeed, as the slide illustrates, smoking cessation treatments are probably the most effective way the NHS spends money.3
NICE estimated the cost-effectiveness of the smoking cessation medicines, NRT and Zyban, to be well below £2,000 per Life Year Gained (LYG) (UK discount rates) and among the most cost-effective of all healthcare inteventions.1
This makes smoking cessation interventions at least 6-fold more cost effective than statin drugs which are routinely used to protect patients from cardiovascular disease (~£11,8004 per LYG)* and at least 15 times lower than the NICE threshold of £30,000 per LYG.5
Smoking cessation interventions therefore offer excellent value for money when compared with some other healthcare interventions.6
Note: * The figure for statins is the net discounted cost per life year saved to the NHS for a year’s treatment of people with a 1.5% risk of coronary heart disease (15% risk over 10 years).
National Institute for Clinical Excellence. Guidance on the use of nicotine replacement therapy (NRT) and bupropion for smoking cessation. London: NICE, March 2002.
Royal College of Physicians. Nicotine addiction in Britain. A report of the Tobacco Advisory Group of the Royal College of Physicians. London: Royal College of Physicians, 2000.
Stapleton J. Cost effectiveness of NHS smoking cessation services, August
Raithatha N, Smith RD. Paying for statins, Br Med J 2004; 328:
Timmins N. Drugs and the NHS's £ question. Financial Times 2001;10 Aug.
Parrott S, Godfrey C. Economics of smoking cessation. BMJ 2004; 328: 947–949.
<£2,0002 £0
Smoking cessation
interventions
Statins
Raithatha N, Smith RD. BMJ 2004; 328:
NICE Smoking Cessation Guidance 2002.

31. NHS Annual Expenditure (£millions)
(approx. £ millions expenditure annually)
7001
This slides illustrates the mismatch in expenditure and cost-effectiveness.
NHS expenditure on statins has risen dramatically in risen years and is currently about £2 million each day (over £700 million annually).1,2
For the period April to September 2004, NHS expenditure on stop smoking services in England was £20.6 million with a further £20 million being spent on the cost of bupropion or NRT on prescription – a total of £40.6million.3
In absolute terms, this means the NHS spends at least 10 times as much on statins as it does on smoking cessation interventions3, where the average cost-effectiveness of statins is only about one-sixth or less that of smoking cessation interventions.4
Greater expenditure on smoking cessation could vastly reduce expenditure on statins by reducing heart disease risk below the level at which treatment with statins is no longer required.4
Dr Roger Boyle. NHS Modernisation Agency conference: excellence in cardiac services, a journey to improvement March 2004.
Gibson L. Move to sell statins over the counter raises concerns. Br Med J 2004; 328; 1221.
Statistics on NHS Stop Smoking Services in England, April-Sept 2004.
The Wanless Review: Securing our future health (Chapter 2: the Health Service in 2022), April 2002.
McNeil A, Bates C. Smoking cessation in primary care….how to spend NHS money much more effectively. Action on Smoking in Health, July 2000.
412
Smoking cessation
Interventions
Statins
Gibson L. BMJ 2004; 328: 1221.
NHS smoking statistics (England), April-Sept 2004.

32. Varenicline (Champix)

33. Varenicline Oral prescription medicine
Specifically designed
Oral prescription medicine
Targets the 42 nicotinic acetylcholine receptor
1. Coe JW. J Med Chem 2005; 48: Dani JA, Harris RA. Nature Neuroscience 2005; 8:

35. Varenicline- partial nicotine agonist
Part blocking
Reduces the pleasurable effects of smoking and potentially the risk of full relapse after a temporary lapse1-4
Part Stimulating
Relieves craving and withdrawal symptoms1-3
1. Coe JW. J Med Chem 2005; 48: Gonzales D et al. JAMA 2006; 296: Jorenby DE et al. JAMA 2006; 296: Foulds J. Int J Clin Pract 2006; 60:

36. ‘Recruitment’ to abstinence
Drug treatment
Varenicline (n=352)
Bupropion SR (n=329)
Placebo (n=344) 60 50 40 30 20 10
Point prevalence abstinence (%)
Time (weeks)
Gonzales D, et al. JAMA 2006;296:47–55

37. Continuous quit rate weeks 9 – 12 (%)
12 week quit rates
Continuous quit rate weeks 9 – 12 (%)
n=692
n=669
n=684
varenicline vs. bupropion OR = 1.87 (95% CI 1.40, 2.34), *p<0.0001
varenicline vs. placebo OR = 3.69 (95% CI 2.88, 4.72), *p<0.0001
Primary endpoint –
Pooled Analysis, comparator studies 1 & 2 (n=2,045)
1. Gonzales DH et al. Presented at 12th SRNT, 15-18th Feb, 2006, Orlando, Florida. Abstract PA9-2.

38. Continuous abstinence rate weeks 9 - 52 (%)
52 week quit rates
Continuous abstinence rate weeks (%)
n=692
n=669
n=684
varenicline vs. bupropion OR = 1.56 (95% CI 1.19, 2.06) †p<0.0013
varenicline vs. placebo OR = 2.82 (95% CI e.06, 3.86), †p<0.0001
Secondary endpoint –
Pooled Analysis Comparator Studies 1 & 2 (n=2,045)
1. Gonzales DH et al. Presented at 12th SRNT, 15-18th Feb, 2006, Orlando, Florida. Abstract PA9-2.

39. End of treatment quit rate
OR 1.70, 95% CI: ; p<0.001

40. 52 week quit rate
OR 1.40, 95% CI: ; p=ns (0.056)

41. 2007/08 English Stop Smoking Services Data
The real world!
2007/08 English Stop Smoking Services Data

42. English Stop Smoking Services 2007/2008:
No. Setting Quit Date
Quit at 4 Weeks
Quit Rate
NRT
474,311
231,601
49%
Zyban
22,348
11,923
53%
Champix
97,259
60,864
63%

43. Adverse events on varenicline compared
with placebo

44. What about nausea? Warn before prescribing Usually self limiting
Take with food or water
Can use anti-emetics ?prochlorperazine (Stemetil)
Adjust dose

45. Varenicline 24 wks Varenicline 12 wks
12 vs 24 Weeks Use: Results
Varenicline 24 wks Varenicline 12 wks
P= OR = 1.34
70.5%
% of Patients
43.6%
49.6%
36.9%
Week
Tonstad S, et al. JAMA. 2006;296:64-71.

46. Who Can Use It? Contraindicated: Hypersensitivity to Varenicline
Not Recommended:
Pregnancy
Under 18 yrs
End stage renal disease

47. Cautions for Use
Severe renal disease as primarily excreted via kidneys (unchanged)
Breast feeding
Epilepsy (not tested)
Psychiatric illness (not tested)
Quitting smoking may exacerbate underlying condition

48. Withdrawal Symptoms
Compared to placebo varenicline significantly reduced :
Depressed mood
Irritability, frustration or anger
Anxiety
Difficulty concentrating
Gonazales D et al. JAMA 2006;296:47-55; Jorenby DE et al. JAMA 2006;296:56-63.

49. Dose of varenicline Days 1 – 3: 0.5mg once daily Days 4 – 7:
0.5mg twice daily
Days 8 – 14:
1mg twice daily
Days 15+
Quit date

50. NICE Guidance on varenicline July 2007
“Varenicline is recommended, within its licensed indications, as an option for smokers who have expressed a desire to quit smoking”
“….should normally be provided in conjunction with counselling and support”
….but if such support is refused, or not available, this should not preclude treatment with varenicline

51. Numbers Needed to Treat (NNT) to Obtain 1 Long-Term Quitter?
Brief advice (<5 mins) = 40(1)
Adding medication to behavioural support…..
NRT = 20(2)
Bupropion = 15(2)
Varenicline = 8(2)
1. West (2006) 2. Cochrane Review. (2007)

52. Numbers Needed to Treat (NNT) to Prevent a Premature Death?
Brief advice (<5 mins) = 80
Adding medication to behavioural support…..
NRT = 40
Bupropion = 30
Varenicline = 16