The essentials of smoking cessation

1
The essentials of smoking cessation
Dr Alex Bobak GP and GPSI in Smoking Cessation
Wandsworth, London
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
Epidemicthe MPOWER package. Geneva, World
Health Organization, 2008 2. Doll R, et al. Br
Med J 2004328151927
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
Whats in a cigarette?
Nicotine
Tar
Arsenic
Ammonia
Toluene
Phenol
DDT
Nitrosamine
Naphthalene
Butane
HydrogenCyanide
Carbonmonoxide
Cadmium
Cigarette smoke contains more than 4,000
chemicals,including over 60 known carcinogens
and metabolic poisons
Ginzel KH. Whats in a cigarette? http//www.acsh.
org/publications/priorities/0102/nicotine.html
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Why do people keep smoking?

• NICOTINE
• ADDICTION

HABIT
SOCIAL
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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

1. Bigelow GE et al. US DHHS 1986. 2. Himbury S
Br Med J 1995. 3. Davidson G et al. Thorax 1992.
4. ASH May 2004.
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Mechanics of nicotine addiction
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NucleusAccumbens(NAcc)
NIC
VentralTegmentalArea(VTA)
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
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On stopping smoking

• It takes 24-48 hours for nicotine to leave the
  body
• It takes 8-12 weeks for the nicotine receptors to
  down-regulate

14
Smokers want to stop
All smokers
70 want to stop1
23 succeed in stopping each year3
30 try each year2
1. Bridgwood et al, General Household Survey
1998. 2. West, Getting serious about stopping
smoking 1997. 3. Arnsten, Prim Psychiatry 1996.
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Stopping smokingWhat works, what doesnt
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A number of tools to aid smoking cessation are
available
Combination of both methods?
NRT nicotine replacement therapy SR
sustained release
17
Long term cessation rates
18
Nicotine replacement therapy
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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 812 weeks with gradual withdrawal

1. Thompson GH, et al. Ann Pharmacother
199832106775 2. Henningfield JE, N Engl J Med
199533311962033. Silagy C, et al. Cochrane
Database Syst Rev 2004. CD000146
CNS central nervous system
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NRT-Dosage and use

• Gum upto 15 or 25/day 2mg or 4mg
• Patch 16 or 24 hours 3 strengths
• S/L tabs upto 40/day 2mg
• Lozenges min 9 max 15/day 2mg or 4mg
• Inhalator 6-12 cartridges/day
• Spray upto 64 sprays/day

21
Plasma nicotine levels contrast between
cigarettes and NRT
25 20 15 10 5 0
Cigarette
Spray
Plasma nicotine (ng/ml)
Gum/Inhalator/Tablet/lozenge
Patch
10
0
20
40
30
50
60
Time (minutes)
Adapted from Tobacco Advisory Group of the Royal
College of Physicians 2000.
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Considerationsfor patients using NRT

• USE ENOUGH! Avoid under-dosing and irregular
  use.
• LONG ENOUGH! Dont stop early, continue 8-12
  weeks.
• NOT A PUFF! Slower and less efficient source
  of nicotine than cigarettes so can not compete.

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Bupropion(Zyban)
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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 athttp//us.gsk.com/products/assets/us_
zyban.pdf 2.Hughes et al. Cochrane Database Syst
Rev 1996. CD000031
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Bupropion treatment regime

• Patients should choose a quit date in the second
  week, for example day 11, or earlier if the
  patient feels ready to stop

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Adverse events on bupropion in smokers with CVD.
McRobbie 2001
Bupropion
Placebo
25
24
20
18
15
13
12
11
11
10
10
6
5
0
Insomnia
Headache
Dry mouth
Nausea
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General population bupropion trial continuous
abstinence rates ()
Tonstad
et al (2001)
plt0.001)
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NICE Guidance on NRT Bupropion April 2002
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• Both bupropion and NRT are considered to be
  among the most cost effective of all healthcare
  interventions.
• Estimates of cost-effectivenessare below 2000
  per Life Year Gained
• NICE April 2002

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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
lt2,0002
0
Smoking cessation interventions
Statins

• Raithatha N, Smith RD. BMJ 2004 328 400-2.
• NICE Smoking Cessation Guidance 2002.

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NHS Annual Expenditure (millions)
(approx. millions expenditure annually)
7001
412
Smoking cessation Interventions
Statins

• Gibson L. BMJ 2004 328 1221.
• NHS smoking statistics (England), April-Sept 2004.

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Varenicline(Champix)
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Varenicline

• Specifically designed
• Oral prescription medicine
• Targets the ?4?2 nicotinic acetylcholine
  receptor

1. Coe JW. J Med Chem 2005 483474-3477. 2. Dani
JA, Harris RA. Nature Neuroscience 2005
81465-1470.
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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 483474-3477. 2.
Gonzales D et al. JAMA 2006 29647-55. 3.
Jorenby DE et al. JAMA 2006 29656-63. 4. Foulds
J. Int J Clin Pract 2006 60571-576.
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Recruitment to abstinence
Drug treatment
Varenicline (n352) Bupropion SR (n329) Placebo
(n344)
60 50 40 30 20 10 0
Point prevalence abstinence ()
0 4 8 12 16 20 24 28 32 36 40 44 48 52
Time (weeks)
Gonzales D, et al. JAMA 20062964755
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12 week quit rates
Continuous quit rate weeks 9 12 ()
n692
n669
n684
varenicline vs. bupropion OR 1.87 (95 CI 1.40,
2.34), plt0.0001 varenicline vs. placebo OR
3.69 (95 CI 2.88, 4.72), plt0.0001
Primary endpoint Pooled Analysis, comparator
studies 1 2 (n2,045)
1. Gonzales DH et al. Presented at 12th SRNT,
15-18th Feb, 2006, Orlando, Florida. Abstract
PA9-2.
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52 week quit rates
Continuous abstinence rate weeks 9 - 52 ()
n692
n669
n684
varenicline vs. bupropion OR 1.56 (95 CI 1.19,
2.06) plt0.0013 varenicline vs. placebo OR 2.82
(95 CI e.06, 3.86), plt0.0001
Secondary endpoint Pooled Analysis Comparator
Studies 1 2 (n2,045)
1. Gonzales DH et al. Presented at 12th SRNT,
15-18th Feb, 2006, Orlando, Florida. Abstract
PA9-2.
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End of treatment quit rate
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52 week quit rate
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The real world!

• 2007/08 English Stop Smoking Services Data

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English Stop Smoking Services 2007/2008
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Adverse events on varenicline compared with
placebo
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What about nausea?

• Warn before prescribing
• Usually self limiting
• Take with food or water
• Can use anti-emetics ?prochlorperazine
  (Stemetil)
• Adjust dose

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12 vs 24 Weeks Use Results
Varenicline 24 wks Varenicline 12 wks
P0.02 OR 1.34
70.5
of Patients
43.6
49.6
36.9
Week
Tonstad S, et al. JAMA. 200629664-71.
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Who Can Use It?

• Contraindicated
• Hypersensitivity to Varenicline
• Not Recommended
• Pregnancy
• Under 18 yrs
• End stage renal disease

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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

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Withdrawal Symptoms

• Compared to placebo varenicline significantly
  reduced
• Depressed mood
• Irritability, frustration or anger
• Anxiety
• Difficulty concentrating

Gonazales D et al. JAMA 200629647-55 Jorenby
DE et al. JAMA 200629656-63.
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Dose of varenicline
Quit date
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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

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Numbers Needed to Treat (NNT) to Obtain 1
Long-Term Quitter?

• Brief advice (lt5 mins) 40(1)
• Adding medication to behavioural support..
• NRT 20(2)
• Bupropion 15(2)
• Varenicline 8(2)

1. West (2006) 2. Cochrane Review. (2007)
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Numbers Needed to Treat (NNT) to Prevent a
Premature Death?

• Brief advice (lt5 mins) 80
• Adding medication to behavioural support..
• NRT 40
• Bupropion 30
• Varenicline 16