smoking cessation and copd philip tønnesen, m.d., dr.med. dept. pulm. medicine gentofte hospital...
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Smoking cessation Smoking cessation and COPDand COPD
Philip Tønnesen, M.D., Philip Tønnesen, M.D., dr.med.dr.med.
Dept. Pulm. MedicineDept. Pulm. MedicineGentofte HospitalGentofte Hospital
Copenhagen, DenmarkCopenhagen, Denmark
I have received consulting and I have received consulting and speaking fees and research speaking fees and research
grants from many companies grants from many companies who develop smoking cessation who develop smoking cessation
medications, products and medications, products and services services
DisclosureDisclosure
DisclosureDisclosure
First line drugs: Efficacy figures First line drugs: Efficacy figures from the Cochrane registerfrom the Cochrane register
Sustained quit rates for 1-year (Risk Ratio)Sustained quit rates for 1-year (Risk Ratio)
NRT versus placeboNRT versus placebo11 1.581.58
(111 studies)(111 studies) (95 % CI, 1.50-1.66)(95 % CI, 1.50-1.66)
Any type of NRTAny type of NRT
Bupropion SR versus placeboBupropion SR versus placebo22 1.851.85
(31 studies)(31 studies)
VareniclineVarenicline versus placeboversus placebo33 2.332.33
(9 studies)(9 studies) (95% CI, 1.95-2.80)(95% CI, 1.95-2.80)
1. Silagy et al. Cochrane Database Syst Rev. 2008;jan 23(0):CD000146.2. Hughes et al. Cochrane Database Syst Rev. 2008;(3) CD0000313. Cahill et al. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD006103.
First line drugs: Efficacy figures from US First line drugs: Efficacy figures from US clinical guidelines clinical guidelines
OR (95%CI)OR (95%CI)Abstinence Abstinence
raterate
PLACEBOPLACEBO aa
1.0 1.0 13.813.8
MONOTHERAPIESMONOTHERAPIES ““
VareniclineVarenicline 3.1 (2.5-3.8) 3.1 (2.5-3.8) 33.233.2
High dose nicotine patch High dose nicotine patch 2.3 (1.7-3.0)2.3 (1.7-3.0) 26.526.5
Nicotine gum (>14 weeks)Nicotine gum (>14 weeks) 2.2 (1.5-3.2)2.2 (1.5-3.2) 26.126.1
BupropionSRBupropionSR 2.0 (1.8-2.2)2.0 (1.8-2.2) 24.224.2
COMBINATION THERAPIES COMBINATION THERAPIES 22
Patch + ad lib NRTPatch + ad lib NRT 3.6 (2.5-5.2)3.6 (2.5-5.2) 36.536.5
Patch + BupropionSRPatch + BupropionSR 2.5 (1.9-3.4)2.5 (1.9-3.4) 28.928.9
Patch + inhalerPatch + inhaler 2.2 (1.3-3.6)2.2 (1.3-3.6) 25.8 25.8
Fiore MC, Bailey WC, Cohen SJ, et al. Clinical Practice Guideline.Treating Tobacco use and Dependence.: 2008 Update. Rockville, MD: U.S. Department of Health
and Human Services. Public Health Service. May 2008.
Smoking prevalence among COPD pt’s Smoking prevalence among COPD pt’s in large RCT trials with ICS/LABAin large RCT trials with ICS/LABA
Study N Age FEV1(%) SmokersStudy N Age FEV1(%) Smokers
INSPIRE 1,323 65 1.3 (39%) INSPIRE 1,323 65 1.3 (39%) 38%38%
ISOLDEISOLDE 751 64 1.4 (50%) 751 64 1.4 (50%) 38%38%
TORCH 5,343 65 1.2 (45%) TORCH 5,343 65 1.2 (45%) 45%45%
TRISTAN 1,465 63 1.4 (45%)TRISTAN 1,465 63 1.4 (45%) 51%51%
EUROSCOP 647 53 2.5 (80%) EUROSCOP 647 53 2.5 (80%) 54%54%
VESTBO 290 59 2.4 (86%)VESTBO 290 59 2.4 (86%) 77%77%
Network meta-analysis of RCT’s in COPD (1)Network meta-analysis of RCT’s in COPD (1)
8 trials included COPD8 trials included COPD
N=7,372N=7,372 Prolonged abstinence rate Prolonged abstinence rate
Lung Health Study (N=5,887) 12 M: 34 % versus 9 % (NRT)Lung Health Study (N=5,887) 12 M: 34 % versus 9 % (NRT) Hilberink (N=392) 6 M: 16 % versus 9 % (NRT)Hilberink (N=392) 6 M: 16 % versus 9 % (NRT) Tønnesen (N=370)Tønnesen (N=370) 12 M: 14 % versus 5 % (NRT) 12 M: 14 % versus 5 % (NRT) Taskin Taskin (N=404) 6 M: 16 % versus 9 % (BUP) (N=404) 6 M: 16 % versus 9 % (BUP) Wagena (N=255) 6 M: 30 % versus 19 %(BUP)Wagena (N=255) 6 M: 30 % versus 19 %(BUP) Pederson (N=64) Pederson (N=64) 6 M: 27 % versus 16 % 6 M: 27 % versus 16 % Crowley (N=49)Crowley (N=49) 6 M: 14 % versus 14 % 6 M: 14 % versus 14 % Brandt (N=56)Brandt (N=56) 12 M: 32 % versus 16 % 12 M: 32 % versus 16 % (Taskin (N=499) 12 M: 19 % versus 6 % (VAR))***(Taskin (N=499) 12 M: 19 % versus 6 % (VAR))***
Eur Respir J 2009;34:634-40Eur Respir J 2009;34:634-40
Efficacy of smoking cessation in COPD (2)Efficacy of smoking cessation in COPD (2)
Odds ratioOdds ratio Nothing/ usual careNothing/ usual care
Counselling aloneCounselling alone 1.82 (0.96-3.34), P=0.071.82 (0.96-3.34), P=0.07
Counselling +antidepres.Counselling +antidepres. 3.32 (1.53-7.21), P=0.0023.32 (1.53-7.21), P=0.002
Counselling + NRTCounselling + NRT 5.08 (4.32-5.97), P<0.0015.08 (4.32-5.97), P<0.001
Counselling + varenicline Counselling + varenicline
(1 study only) (CHEST, 2011)(1 study only) (CHEST, 2011)
4.04 (2.13-7.67) P<0.0014.04 (2.13-7.67) P<0.001
Eur Respir J 2009;34:634-40
COPD cont.COPD cont.
Smoking cessation in COPDSmoking cessation in COPD
Tønnesen et al, Chest 2006:Tønnesen et al, Chest 2006:
Nurse-conducted smoking cessation in patients with Nurse-conducted smoking cessation in patients with COPD, using nicotine sublingual tablets and behavioral COPD, using nicotine sublingual tablets and behavioral supportsupport
Smoking cessation/reduction in COPD Smoking cessation/reduction in COPD (Tønnesen et al. Chest, 2006)(Tønnesen et al. Chest, 2006)
370 COPD patients370 COPD patients
Age :62 yearsAge :62 years
FEVFEV11: 1.57 (56 % predicted): 1.57 (56 % predicted)
Cigarettes/day: 20Cigarettes/day: 20
FTND: 6.4FTND: 6.4
High – low support, NRT – placebo 12 weeksHigh – low support, NRT – placebo 12 weeks
Smoking cessation in COPDSmoking cessation in COPD
NRT versus placebo:NRT versus placebo:
6 months quit rate: 6 months quit rate: 23 % vs 10 %23 % vs 10 %
12 months quit rate:12 months quit rate: 17 % vs 10 % (OR 2.0)17 % vs 10 % (OR 2.0)
2 week to 12 months: 14 % vs. 5 %2 week to 12 months: 14 % vs. 5 %
SGRQ in COPD (12 Months)SGRQ in COPD (12 Months)
QuittersQuitters Reducers Reducers SmokersSmokers
Symptoms -28Symptoms -28 -21 -21 -2 -2
ActivityActivity -6-6 -8 -8 -2 -2
ImpactImpact -8-8 -5 -5 -4 -4
Total score -10.9Total score -10.9 -8.5 -8.5 -2.9 -2.9
Varenicline and COPD (mild-moderate)Varenicline and COPD (mild-moderate)Chest 2010, Tashkin et alChest 2010, Tashkin et al
12 weeks 12 weeks VareniclineVareniclinePlaceboPlacebo
NumbersNumbers 250250 254254
AgeAge 5757 5757
FEV1 % FEV1 % 71 %71 % 69 %69 %
Cig/dayCig/day 2525 2424
QuittersQuitters
3-12 Months3-12 Months 18.6 %18.6 % 5.6 %5.6 %
Effect of smoking cessation interventionsEffect of smoking cessation interventions
GPs short advice: GPs short advice: 2 %2 %
Intensive behavioural support: Intensive behavioural support: 7 %7 %
Self-help materialSelf-help material 1 %1 %
Proactive telephone counselingProactive telephone counseling 2 %2 %
Nicotine productsNicotine products 7 %7 %
BupropionBupropion 9 %9 %
VareniclineVarenicline 11 %*11 %*
Intensive support+NRT/bupropion Intensive support+NRT/bupropion 13 -19 %13 -19 %
Intensive support + vareniclineIntensive support + varenicline 18 - 22 %*18 - 22 %*
Modified from West et al, Thorax 2000; *Cochrane Library 2007-2008
Lung Health study 1 (1)Lung Health study 1 (1)
10 clinical centers in US10 clinical centers in US
12 group sessions during the first 10 weeks12 group sessions during the first 10 weeks
4 sessions in the first week4 sessions in the first week
Target quit dayTarget quit day
CounsellingCounselling
Aggresive use of Nicotine 2-mg chewing gumAggresive use of Nicotine 2-mg chewing gum
Follow-up program with focus on relapse prevention, Follow-up program with focus on relapse prevention, stress mangement, weight gainstress mangement, weight gain
Formal re-treatment when relapsedFormal re-treatment when relapsed
Lung Health Study: Point prevalenceLung Health Study: Point prevalence
Recycling of smokers every 4 months in 5 years! NRT:2mg-GUM
(N=5587)
0
5
10
15
20
25
30
35
40%
qu
itte
rs
1-year 2-year 3-year 4-year 5-year
S-IU-C
Anthonisen NR, Connett JE, Kiley JP,et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study. JAMA 1994; 272: 1497‑1505.
8 weekly individual visits with 2 mg nico-gum (2)
Mean FEVMean FEV1 1 quitters and smokers (diff. 11-yrs: (3)quitters and smokers (diff. 11-yrs: (3)380 ml; diff smokers and interm: 100 ml;380 ml; diff smokers and interm: 100 ml;
0
0,5
1
1,5
2
2,5
3
3,5
Entry 1-year 2-year 3-year 4-year 5-year 11-years
FE
V-1 Quitters
Smokers
Smoking Cessation: Effects on Smoking Cessation: Effects on Mortality (4)Mortality (4)
CHD=coronary heart disease; CVD=cardiovascular disease.
4
2
1
0
Rat
e o
f D
eath
per
100
0 P
erso
n-Y
ears
OtherCHD CVD Lung Cancer
Other Cancer
Respiratory Disease
Unknown
Causes of Death
Sustained Quitter Intermittent Quitter Continuing Smokers
3
Athonisen et al. Ann Intern Med. 2005;142(4):233-239.
0
1
2
3
4
5
6
7
8
9
10
0 1 2 3 4 5Year
Me
an
we
igh
t ch
an
ge
Male smokersMale quittersFemale smokersFemale quitters
Weight change in the Lung Health Study (5)
Intensity of interventionIntensity of intervention
Minimal (<3 minutes) is effective (A)Minimal (<3 minutes) is effective (A)
Dose-response effect (person-to-person) (A)Dose-response effect (person-to-person) (A)
Four or more sessions are especially effective (A)Four or more sessions are especially effective (A)
Fiore MC, Bailey WC, Cohen SJ, et al. Clinical Practice Guideline.Treating Tobacco use and Dependence.: 2008 Update. Rockville, MD: U.S. Department of Healthand Human Services. Public Health Service. May 2008.
Brief intervention = 2 questionsBrief intervention = 2 questions
””Do you smoke?” and if yesDo you smoke?” and if yes
” ” Have you considered to quit?”Have you considered to quit?”
Very simple and short:Very simple and short:
It’s the patients project to quit but your obligation to It’s the patients project to quit but your obligation to support the smoker in the quitting attemptsupport the smoker in the quitting attempt
Arrange referal to smoking cessation: a new Arrange referal to smoking cessation: a new appointment, smoking cessation clinic, etc. appointment, smoking cessation clinic, etc.
Good idea to have a card with address and phone Good idea to have a card with address and phone numbernumber
Smoking cessation by hospitalization (1) Smoking cessation by hospitalization (1) COPD patients: COPD patients: Hospitalization (N=247) vs. Usual careHospitalization (N=247) vs. Usual care (N=231) (N=231)
FEV1 % pred.:75 % Age: 52 yearsFEV1 % pred.:75 % Age: 52 years
Hospitalization in Åre Hospital in Northern SwedenHospitalization in Åre Hospital in Northern Sweden
11 days, third day: target quit day, NRT; exercise, 1 hour daily meeting 11 days, third day: target quit day, NRT; exercise, 1 hour daily meeting with trained cessation nurses, educational program followed by weekly with trained cessation nurses, educational program followed by weekly telephone calls by nursestelephone calls by nurses
After 2-3 months 2-4 days in hospital After 2-3 months 2-4 days in hospital
Sundblad, Larsson K, Nathell L, Nic Tob Res 2008;10:883-890Sundblad, Larsson K, Nathell L, Nic Tob Res 2008;10:883-890
Smoking cessation by hospitalization (2)Smoking cessation by hospitalization (2)
Smoking cessation groupSmoking cessation group
1-year quit rate: 52 %1-year quit rate: 52 %
3-year quit rate: 38 %3-year quit rate: 38 %
Used NRT: 28 %Used NRT: 28 %
Used BUP: 5 %Used BUP: 5 %
Sundblad, Larsson K, Nathell L, Nic Tob Res Sundblad, Larsson K, Nathell L, Nic Tob Res 2008;10:883-8902008;10:883-890
Usual careUsual care
1-year quit rate: 7 %1-year quit rate: 7 %
3-year quit rate: 10 %3-year quit rate: 10 %
Used NRT: 14 %Used NRT: 14 %
Used BUP: 5 %Used BUP: 5 %
What are we doing today in smoking What are we doing today in smoking cessation?cessation?
Cost-effectivenessCost-effectiveness
Meta-analysis of cost effectivness of smoking Meta-analysis of cost effectivness of smoking cessation after 25 yearscessation after 25 years
Quit rate Cost per QUALYQuit rate Cost per QUALYUsual careUsual care 1.4 % 1.4 %Minimal counsellingMinimal counselling 2.6 % 2.6 % 16.900 Euros 16.900 EurosIntensive counsellingIntensive counselling 6.0 % 6.0 % 8.200 Euros 8.200 EurosIntesive c. + pharma. 12.3 % 2.400 EurosIntesive c. + pharma. 12.3 % 2.400 Euros
Hoogendoorn M et al. Thorax 2010;65:711-718
The US experimentThe US experiment
Re-imbursement Re-imbursement
InInssurance coverage of smoking cessationurance coverage of smoking cessation r resulted inesulted in::1.1. Higher rates of use of evidence-based therapies Higher rates of use of evidence-based therapies 2.2. Higher Higher overall overall quit ratesquit rates3.3. Smoking Smoking cessation coverage in US 25 % (1997) to 90 % cessation coverage in US 25 % (1997) to 90 %
(2003)(2003)22
1. Kaper et al 2006 1. Kaper et al 2006 Pharmacoeconomics 24(5): 453-64Pharmacoeconomics 24(5): 453-64
2. McPhillips-Tangum et al. Prev Chronic Dis 2006 3; 1-11. Available from: 2. McPhillips-Tangum et al. Prev Chronic Dis 2006 3; 1-11. Available from: http://www.cdc.gov/pcd/issues/2006/jul/05_0173.htmhttp://www.cdc.gov/pcd/issues/2006/jul/05_0173.htm
ERS Guidelines ERS Guidelines
Aggressive smoking cessation is recommended i.e. Aggressive smoking cessation is recommended i.e. varenicline, NRT, bupropionSR, and counseling and varenicline, NRT, bupropionSR, and counseling and recycling recycling
Data from NIV-COPD national register in Data from NIV-COPD national register in Denmark for 2010Denmark for 2010
Ambulatory COPD patients in DKAmbulatory COPD patients in DK
Asked about smoking habitAsked about smoking habit Oct.-Dec. July-Sept.Oct.-Dec. July-Sept. Jan.-JuneJan.-June
(N=6167) 75 % (N=6167) 75 % 75 % 75 % 66 % 66 %
Adviced to quit smokingAdviced to quit smoking
(1467)(1467) 91 % 91 % 92 % 92 % 88 % 88 %
Conclusion smoking cessation in COPDConclusion smoking cessation in COPD
Counselling + NRT increases quit rateCounselling + NRT increases quit rate
Counselling + BupropionSR increases quit rateCounselling + BupropionSR increases quit rate
Counselling + Varenicline increases quit rateCounselling + Varenicline increases quit rate
(study under publication)(study under publication)
Retreatment after relapse increases long-term quit rateRetreatment after relapse increases long-term quit rate
Expect a 1-year quit rate of 15-35 % (point prevalence)Expect a 1-year quit rate of 15-35 % (point prevalence)
Tønnesen et al. ERS guidelines. ERJ 2008Tønnesen et al. ERS guidelines. ERJ 2008
Take home meassage: Smoking Take home meassage: Smoking cessation in COPDcessation in COPD
Counselling + NRT/ BupropionSR or Varenicline for 6 Counselling + NRT/ BupropionSR or Varenicline for 6 months should be perscribed to COPD smokers months should be perscribed to COPD smokers
Retreatment if the COPD patient relapseRetreatment if the COPD patient relapse
Tønnesen et al. ERS guidelines. ERJ 2008Tønnesen et al. ERS guidelines. ERJ 2008
“Last Request: Please Don’t Smoke” My step-father asked me to take this picture of him after he regained consciousness in ICU. He lost the
fight with lung disease (Asbestosis, COPD, and Pnuemonia) Friday morning. I will be away for a little while