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The essentials of smoking cessation Dr Alex Bobak GP and GPSI in Smoking Cessation Wandsworth, London.

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Presentation on theme: "The essentials of smoking cessation Dr Alex Bobak GP and GPSI in Smoking Cessation Wandsworth, London."— Presentation transcript:

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 world 1 Smoking is the largest preventable cause of disease and premature death in the world 1 More than 50% of long-term smokers die prematurely due to smoking-related diseases 2 More than 50% of long-term smokers die prematurely due to smoking-related diseases 2 1. WHO Report on the Global Tobacco Epidemic: the MPOWER package. Geneva, World Health Organization, 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 13 million adults smoke in the UK HALF of young adults become long term smokers HALF of young adults become long term smokers Smoking kills HALF of long term smokers Smoking kills HALF of long term smokers

6 Whats in a cigarette? NicotineTarArsenic Carbon monoxide Cadmium Hydrogen Cyanide Cigarette smoke contains more than 4,000 chemicals, including over 60 known carcinogens and metabolic poisons Ginzel KH. Whats in a cigarette? AmmoniaToluene Phenol Nitrosamine NaphthaleneButane DDT

7 Why do people keep smoking? NICOTINEADDICTION HABIT SOCIAL

8 The power of nicotine addiction 60% smoke again post MI (40% within 2 days) 60% smoke again post MI (40% within 2 days) 50% smoke again post laryngectomy 50% smoke again post laryngectomy 50% smoke again post pneumonectomy 50% smoke again post pneumonectomy 80% of women do not stop smoking during pregnancy 80% of women do not stop smoking during pregnancy 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 α4α4 β2β2 α4α4 β2β2 β2β2 NIC Nicotine Dopamine Nucleus Accumbens (NAcc) Ventral Tegmental Area (VTA) NIC

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

14 Smokers want to stop Allsmokers ~2–3% succeed in stopping each year 3 ~70% want to stop 1 ~30% try each year 2 1. Bridgwood et al, General Household Survey West, Getting serious about stopping smoking Arnsten, Prim Psychiatry 1996.

15 Stopping smoking: What works, what doesnt

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

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

18 Nicotine replacement therapy

19 Available in six different forms Available in six different forms Based on nicotine weaning 1 Based on nicotine weaning 1 Significantly reduces withdrawal symptoms and cravings vs placebo 2 Significantly reduces withdrawal symptoms and cravings vs placebo 2 Significantly increases smoking cessation rate vs placebo (odds ratio = 1.77) 3 Significantly increases smoking cessation rate vs placebo (odds ratio = 1.77) 3 Treatment lasts 8–12 weeks with gradual withdrawal 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 CD CNS = central nervous system

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

21 Plasma nicotine levels – contrast between cigarettes and NRT Plasma nicotine (ng/ml) Cigarette Spray Gum/Inhalator/Tablet/lozenge Patch Time (minutes) Adapted from: Tobacco Advisory Group of the Royal College of Physicians 2000.

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

23 Bupropion (Zyban)

24 Bupropion SR Non-nicotine prescription tablet originally developed to treat depression 1 Non-nicotine prescription tablet originally developed to treat depression 1 Modifies dopamine levels and noradrenergic activity 1 Modifies dopamine levels and noradrenergic activity 1 Significantly increases smoking cessation rate vs placebo (odds ratio = 1.94) 2 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 Patients should choose a quit date in the second week, for example day 11, or earlier if the patient feels ready to stop Patients should choose a quit date in the second week, for example day 11, or earlier if the patient feels ready to stop

26 Adverse events on bupropion in smokers with CVD. McRobbie InsomniaHeadacheDry mouthNausea BupropionPlacebo

27 General population bupropion trial: continuous abstinence rates (%) Tonstadet al (2001) wks4-12 wks4-26 wks4-52 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. 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 Estimates of cost- effectiveness……are below £2000 per Life Year Gained NICE April 2002

30 Cost Per Life Year Gained £11,800 1 <£2,000 2 £0 £2,000 £4,000 £6,000 £8,000 £10,000 £12,000 £14,000 Statins Smoking cessation interventions 1.Raithatha N, Smith RD. BMJ 2004; 328: NICE Smoking Cessation Guidance Cost per Life Year Saved

31 NHS Annual Expenditure (£millions) Statins Smoking cessation Interventions (approx. £ millions expenditure annually) Gibson L. BMJ 2004; 328: NHS smoking statistics (England), April-Sept 2004.

32 Varenicline (Champix)

33 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: Varenicline

34

35 Part Stimulating Relieves craving and withdrawal symptoms 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: Part blocking R educes the pleasurable effects of smoking and potentially the risk of full relapse after a temporary lapse 1-4 Varenicline- partial nicotine agonist

36 Gonzales D, et al. JAMA 2006;296:47– Point prevalence abstinence (%) Time (weeks) Varenicline (n=352) Bupropion SR (n=329) Placebo (n=344) Drug treatment Recruitment to abstinence

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

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

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 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 NRT474,311231,60149% Zyban22,34811,92353% Champix97,25960,86463%

43 Adverse events on varenicline compared with placebo

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

45 Week % of Patients 12 vs 24 Weeks Use: Results Tonstad S, et al. JAMA. 2006;296: % 36.9% P=0.02 OR = 1.34 Varenicline 24 wks Varenicline 12 wks 70.5% 49.6%

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

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

48 Withdrawal Symptoms Compared to placebo varenicline significantly reduced : nDepressed mood nIrritability, frustration or anger nAnxiety nDifficulty 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+ 1mg twice daily 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 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 ….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 ….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) Brief advice (<5 mins) = 40 (1) Adding medication to behavioural support….. Adding medication to behavioural support….. NRT = 20 (2) NRT = 20 (2) Bupropion = 15 (2) Bupropion = 15 (2) Varenicline = 8 (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 Brief advice (<5 mins) = 80 Adding medication to behavioural support….. Adding medication to behavioural support….. NRT = 40 NRT = 40 Bupropion = 30 Bupropion = 30 Varenicline = 16 Varenicline = 16


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