Smoking Cessation within tobacco control:

Own contributions

C T Bolliger

FHS, US 25 May 2012

Projected annual tobacco-related deaths

Year Total 1.World 3.World

1950 300.000 300.000 -

1965 1.000.000 900.000 100.000

1975 1.500.000 1.300.000 200.000

1995 3.000.000 2.000.000 1.000.000

2000 3.500.000 2.400.000 1.100.000

2025 10.000.000 3.000.000 7.000.000 Mackay JL. Tuber Lung Dis 1994;75:8-24

21st century mortality prediction: 1 Billion

Reference: Joossens L, Raw M. The Tobacco Control Scale: a new scale to measure country activity.

Tob Control 2006; full PDF available at: http://tobaccocontrol.bmj.com/content/15/3/247.full.pdf

Three-pronged approach

Counselling

Hospital QuitSupport (HQS) in Switzerland

Regional smoking cessation Clinics in SA

Guidelines

For Africa/Middle East Ali AY. Respiration. 2012;83(5):423-32

Pharmaceutical Aids

Smoking Reduction

Varenicline

VarNic Study

Map of Switzerland

Bolliger CT. Swiss Med Wkly. 2008 Jul 26;138(29-30):427-31

WEB Search/Phone call

Offers for 3 risk factors:

Obesity (nutrition, alimentation, Ernaehrung)

Hypertension

Smoking 102 US hospitals: web sites: 30%, phone call:47% Denny JT. CHEST 2002;122:692

Bolliger CT. Swiss Med Wkly. 2008 Jul 26;138(29-30):427-31

Personal Visits to Hospitals

►Letter to hospital director and head of Internal Medicine (or medical director) Describe project

Announce visit of HQS team (CTB, XvB)

►Visit all hospitals 10/05 – 1/06

explain project

Motivate for establishment of smoking cessation clinic

Bolliger CT. Swiss Med Wkly. 2008 Jul 26;138(29-30):427-31

WEB

Telephone Visit

Obesity

29/44 (65.9%)

42/44 (95.5%)

42/44 (95.5%)

Hypertension

19/44 (43.2%)

43/44 (97.7%)

43/44 (97.7%)

Smoking

6/44 (13.6%)

10/44 (22.7%)

9/44 (20.5%)

Medical offer 17.1.06

Bolliger CT. Swiss Med Wkly. 2008 Jul 26;138(29-30):427-31

Smoking Cessation Clinics in SA

►Planned: TAH, Paarl, Worcester..and primary care centres around peninsula

►In cooperation with Mark Cotton, Bob Mash

►NIH refused to look at R01 proposal

because of lack of Northern hemisphere expert…what a joke!

we are now looking at Swiss connections

Nicotine Replacement Therapy (NRT)

Smoking Reduction with NRT

► 400 smokers, 18y, 15 cig/day, CO 10ppm unwilling or unable to quit

►Recommended: 50% no of cig/d

► 200 nicotine/200 placebo inhaler 18/12

► Success: 50% no of cig/d, any CO

Bolliger BMJ 2000;321:329-33

Smoking Reduction with NRT

►Results (sustained reduction):

month n (%) active n (%) placebo p

4 52 (26) 18 (9) <0.001

12 26 (13) 8 (4) 0.002

24 19 (9.5) 6 (3) 0.012

Bolliger BMJ 2000;321:329-33

Varenicline

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

a4 b2 b2 b2 a4

a4b2 nicotinic

acetylcholine

receptor (nAChR)

Varenicline (Champix ®)

Specifically developed for smoking cessation

Partial agonist of the a4b2-nicotinic acetylcholine

receptor, combines agonistic and antagonistic

properties in one drug

► As agonist: reduces withdrawal symptoms

► As antagonist: blocks reward pathway after

nicotine uptake

As a partial agonist of α4β2 nAChRs, varenicline:

• Stimulates dopamine release from the VTA at a lower level than nicotine

• Blocks nicotine antagonistically from binding these receptors2

Varenicline: A Highly Selective a4b2 Nicotinic Acetylcholine Receptor Partial Agonist

1. Picciotto MR, et al. Nicotine Tob Res. 1999;Suppl 2:S121-S125. 2. Coe JW, et al. J Med Chem. 2005;48:3474-3477.

Binding of nicotine at the α4β2 nicotinic acetylcholine receptor (nAChR) in the VTA is believed to cause release of dopamine at the nAcc1

Nicotine Varenicline

Copyright restrictions may apply.

Gonzales, D. et al. JAMA 2006;296:47-55

7-Day Point Prevalence Abstinence

Does it work in SA?

► A multicenter, randomized, double-blind, placebo-controlled clinical trial conducted at 42 sites in 11 countries

Latin America: Brazil, Colombia, Costa Rica, Mexico, Venezuela

Africa: South Africa, Egypt

Middle East: Jordan, Lebanon, Saudi Arabia, United Arab Emirates

► Treatment

12 weeks of treatment with varenicline (0.5 mg once daily for 3 days, 0.5 mg BID for 4 days, then 1.0 mg BID) or placebo

Varenicline (1 mg BID, up-titration during first week)

Study Design (1080)

Treatment Phase Non-treatment Phase

Placebo

Screening Visit

Baseline Randomization

12 24

Primary Endpoint: 4-week continuous abstinence rate Weeks 9–12 (CO-confirmed)

Secondary Endpoint: Continuous abstinence rate Weeks 9–24 (CO-confirmed)

9 Week

Target Quit Date at Week 1 visit

1

Weeks 2, 3, 4, 6, 8, 10, 12, 13, 16, 20 and 24 Clinic Visits

Telephone calls TQD+3, Weeks 14, 18 and 22

CO-Confirmed CARs Bolliger CT. Clin Ther. 2011;33(4):465-77

OR: 5.76* (95% CI 3.74 to 8.88), P<0.0001*

53.59

39.74

18.69

13.13

0

10

20

30

40

50

60

Weeks 9-12 Weeks 9-24

Varenicline 1 mg BID (n=390)

Placebo (n=198)OR: 4.78* (95% CI 2.97 to 7.68), P<0.0001*

*Odds ratio and P values obtained from logistic regression model including the main effects of treatment and country

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VarNic:

VarNic study: varenicline ± nicotine patch:

Never done

SA multicenter study (n=438, 7 sites, 6/12)

5 Cape Town, 1 JHB, 1 Durban

Last patient in: 31/3/2012: out: 30/9/2012

First impressions:

Good safety

......and do not forget....