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
Medical offer 17.1.06 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%) 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 b2 b2 a4 b2 a4 a4b2 nicotinic acetylchol ine receptor (nachr) 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
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
Varenicline: A Highly Selective a4b2 Nicotinic Acetylcholine Receptor Partial Agonist Nicotine Varenicline Binding of nicotine at the α4β2 nicotinic acetylcholine receptor (nachr) in the VTA is believed to cause release of dopamine at the nacc 1 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. 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 receptors 2
7-Day Point Prevalence Abstinence Gonzales, D. et al. JAMA 2006;296:47-55 Copyright restrictions may apply.
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
Study Design (1080) Treatment Phase Varenicline (1 mg BID, up-titration during first week) Non-treatment Phase Screening Visit Week 1 Placebo 9 12 24 Primary Endpoint: 4-week continuous abstinence rate Weeks 9 12 (CO-confirmed) Baseline Randomization Target Quit Date at Week 1 visit Secondary Endpoint: Continuous abstinence rate Weeks 9 24 (CO-confirmed) Clinic Visits Weeks 2, 3, 4, 6, 8, 10, 12, 13, 16, 20 and 24 Telephone calls TQD+3, Weeks 14, 18 and 22
Continuous Abstinence (%) CO-Confirmed CARs Bolliger CT. Clin Ther. 2011;33(4):465-77 60 50 40 30 20 10 OR: 5.76* (95% CI 3.74 to 8.88), P<0.0001* 53.59 18.69 39.74 Varenicline 1 mg BID (n=390) Placebo (n=198) OR: 4.78* (95% CI 2.97 to 7.68), P<0.0001* 13.13 0 Weeks 9-12 Weeks 9-24 *Odds ratio and P values obtained from logistic regression model including the main effects of treatment and country
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...