Tobacco Cessation

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Tobacco Cessation

• Daniel Seidensticker

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In Kuwait

• 5 STEMIs in pts lt 35 yo
• Only risk factor
• TOBACCO USE

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30 yo male

• No risk factors
• Your risk of having a cardiovascular event in the
  next 10 years is lt 1.
• Smoking
• Your risk of having a cardiovascular event in the
  next 10 years is 2.
• Hypertension
• Your risk of having a cardiovascular event in the
  next 10 years is 2.
• Hyperlipidemia (total 240, HDL 40)
• Your risk of having a cardiovascular event in the
  next 10 years is 2.

http//www.med-decisions.com/cvtool/active/patient
/riskcalc.php
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• How much time/effort do we spend checking liver
  panels for statins?
• How many visits are follow-up for bp checks?
• How many GI bleeds are caused by ASA primary
  prevention?
• How much time do YOU spend talking about tobacco?
• How many times do YOU document it as a problem?
• Do you even think it is YOUR problem to address??

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Physician Advice ???

• 1989-1990 52 of smokers received counseling
• 3.6 surveyed said physicians helped them quit
• 1998-99 survey 64 of smokers in Wisconsin
  received advice to quit

Frank E. Predictors of physician smoking
cessation advice. JAMA 1991266(22)3139-3144 Marbe
lla et. Al. Wisconsin physicans advising smokers
to quitWMJ 2003102(5)41-45
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Paradigm shiftWe need to consider

• Tobacco dependence as a chronic problem
• Tobacco dependence as important as HTN,
  Hyperlipidemia
• Tobacco dependence as a problem we must address

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• Why is tobacco so bad?
• Does quitting really make a difference?
• How do we get people to quit??

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Does Cigarette smoke affect atherosclerosis?

• Increase plaque in aorta seen on TEEs in smokers
• ARIC trial looked at gt 10,000 pts carotid intimal
  thickness over 3 year period
• Smokers gt 50 increase in thickness
• Secondhand smokers gt 20 increase

JAMA 1998 279 (2) 119
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HOW does cigarette smoking do this?

• Modification of Lipids
• Vasomotor dysfunction
• Inflammation
• Prothrombotic

Ambrose JA, Barua RS. The pathophysiology of
cigarette smoking and cardiovascular disease
JACC 43 (10) 2004 1731-1737
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Modification of Lipids

• Smokers generally have higher LDL/TG
• Smokers generally have lower HDL
• Increases oxidative modification of LDL
• Actively taken up by macrophages ? foam cells

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Vasomotor dysfunction

• Decreased vasodilatory function
• Decreased NO availability
• Endothelial cells exposed to smokers sera
• Smoking alters the expression and activity of
  endothelial NO synthase enzyme
• NO also thought to regulate cytokines/inflammation

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Inflammation

• CS increased WBC, CRP, TNF-a, and IL-6
• Endothelium
• Increased leukocyte recruitment
• Higher levels of ICAM-1, VCAM-1
• Cell-cell interaction
• CSE 70-90 increase in adherence of monocytes to
  umbilical cells in culture
• CSE 200 increase in rate of transendothelial
  migration of monocyte-like cells across umbilical
  cell monolayer
• Smoking fuels the fire of inflammation in the
  blood and at the vessel wall

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Prothrombotic

• Platelet dysfunction
• Increased stimulated/spontaneous aggregation
• Decreased availability of platelet-derived NO
• Prothrombotic
• Higher fibrinogen, tissue factor levels
• Decreased TF pathway inhibitor-1 (TFPI-1) levels
• Decreased fibrinolysis
• Decreased basal and substance-P-stimulated t-PA
  release

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• Lipid metabolism
• Helps create foam cells, facilitate initiation of
  plaque
• Vasomotor dysfunction
• Vasoconstriction, less vasodilation
• Inflammation
• fuels the fire of inflammation in the blood and
  at the vessel wall
• Thrombosis
• dysfunctional thrombo-hemostatic mechanism(s)
  that promote the initiation and/or propagation of
  thrombus formation and limit its effective
  dissolution.

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• Modification of Lipids -- STATINS
• Vasomotor dysfunction NTG, etc
• Inflammation -- STATINS, ASA
• Prothrombotic ASPIRIN, PLAVIX

Ambrose JA, Barua RS. The pathophysiology of
cigarette smoking and cardiovascular disease
JACC 43 (10) 2004 1731-1737
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.
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What about smokeless tobacco or secondhand smoke?

• INTERHEART study
• Smokeless OR 2.23 (1.41-3.52)
• Smoking smokeless OR 4.09 (2.98-5.61)
• Secondhand smoke
• OR1.24 (1.17-1.32) for low exposure (lt7
  hrs/week)
• OR1.62 (1.45-1.81) for high exposure
  (gt21hrs/week)

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Does Quitting Make a Difference?
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.
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It is never too late to quit
Vollset et. Al. Annals of Internal Medicine 2006
144(6) 381-389
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Short term results
Teo et al. INTERHEART Lancet 2006 368647-658
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Our population
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What can we do??

• Brief counseling
• Pharmacotherapy
• Behavioral therapy
• Combined approaches

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lt 3 minutes counseling.

• Brief advice vs. no advice
• 2.5 absolute difference in cessation rate
• 2.5 success 10,000 pts ? 250 pts tobacco free
• 20 success with formal program ?
• 1250 pts have to complete program to yield 250
  pts tobacco free

Silagy, C. Stead, LF. Cochrane databaseSyst
Rev 2006 (3)
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Impact of Physicians Advice to Quit (n 7
studies)
Odds Ratio (95) CI
Estimated Abstinence Rate

Advice
No advice to quit (reference group)
7.9
1.0
Physician advice to quit
10.2
1.3 (1.1-1.6)
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Efficacy of Interventions Delivered by Various
Types of Clinicians (n 29 Studies)
Estimated Abstinence Rate
Odds Ratio (95) CI

Type of Clinician
No clinician (reference group)
10.2
1.0
1.1 (0.9-1.3)
10.9
Self-help
Non-physician clinician
1.7 (1.3-2.1)
15.8
19.9
2.2 (1.5-3.2)
Physician clinician
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pharmacotherapy
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Smoking Cessation Pharmacotherapy
Pharmacotherapy combined with behavioral support
provides the best success rate
Other nicotine replacement therapy options
include nicotine gum, lozenge, inhaler, nasal
spray
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PharmacotherapyNicotine Replacement Therapy
(NRT)

• Nicotine patch most extensively studied
• Nicotine patch reduces thrombosis profile
• 164 pts vs. 33 controls and patch and gum
• Improvements in fibrinogen levels, HCT, WBC and
  reactive capillary blood flow at 6 months among
  abstainers
• Nicotine patch reduces coronary vasospasm
• Known smokers in cath lab vasoconstriction to
  cold pressors, but no change with nicotine gum

Joseph AM, Fu SS. Safety issues in
pharmacotherapy for smoking in patients with
cardiovascular disease Progress in
Cardiovascular Disease 2003 45 (6) 429-441
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What about pts with CAD?

• Is it safe?
• 21 mg patch no hemodynamic/procoagulant effect
• No significant change in HR, BP, fibrinogen,
  lipid levels in long term smokers

Mahmarian et al JACC 1997 30(1) 125-130
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• 40 pts (35 men)
• known CAD
• 1 ppd hx
• gt 5 defect on ETT-thallium
• Anti-anginals stopped
• Exclusion PTCA/bypass lt 3 months prior
• Valvular disease, unstable angina

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What about pts s/p MI??

• Multicenter, gt 45 yo
• h/o MI, PTCA, CABG
• OR
• CHF, cor pulmonale, arrhythmia, PVD, CVA
• EXCLUSION
• MI, UA, CABG, PTCA/PCI 2 weeks prior

Joseph et al. NEJM 19963351792-1798
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What about pts with MI?

• STEMI GUIDELINES
• Class I1. Patients recovering from STEMI who
  have a history of cigarette smoking should be
  strongly encouraged to stop smoking and to avoid
  secondhand smoke. Counseling should be provided
  to the patient and family, along with
  pharmacological therapy (including nicotine
  replacement and bupropion) and formal smoking
  cessation programs as appropriate. (Level of
  Evidence B)

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Pregnancy and the patch??

• Relative contra-indication

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Non-nicotine replacement therapy
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Efficacy of Bupropion SR (n 2 Studies)
Odds Ratio (95) CI
Estimated Abstinence Rate

Pharmacotherapy
Placebo (reference group)
1.0
17.3
30.5
2.1 (1.5 - 3.0)
Bupropion SR
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Bupropion (Zyban)

• Lowers the seizure threshold
• Risk in pts without h/o seizures 0.1
• Significant drug-drug interactions
• Inhibits CYP2D6 isoenzymes
• Can affect Beta-blockers, anti-arrhythmics, SSRIs

Joseph AM, Fu SS. Safety issues in
pharmacotherapy for smoking in patients with
cardiovascular disease Progress in Cardiovascular
Disease 2003 45 (6) 429-441
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Bupropion (Zyban)

• Most common side effects
• Vivid dreams (Kuwaiti experience)
• Insomnia
• Dry mouth
• Headache, nausea/vomiting, constipation and
  tremor (no difference compared w/ placebo)

Thomson, CC and Rigotti, NA . Hospital- and
clinic- based smoking cessation interventions for
smokers with Cardiovascular disease. Progress
in cardiovascular diseases 2003 45 (6)459-479
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Smoking Cessation Pharmacotherapy
Pharmacotherapy combined with behavioral support
provides the best success rate
Other nicotine replacement therapy options
include nicotine gum, lozenge, inhaler, nasal
spray
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Chantix (Varenicline)

• Partial agonist binds selectively to a4b2
  nicotinic acetylcholine receptors with greater
  affinity than nicotine with less stimulation
• Stimulates release of dopamine (which is felt to
  be reward related to smoking)
• 1 mg twice daily compared with placebo and
  bupoprion in 3 DB/PC/Randomized trials
• Cessation _at_ 12 weeks nine months later
• 12 placebo 8-10 placebo
• 30 zyban 15-16 zyban
• 44 varenicline 23-23 varenicline

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Getting the patient to quit
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• 8 randomized trials showed that extensive
  training programs increased smokers identified
  and offered advice, but no long term abstinence
• Training can be expensive
• Simply providing programs for health care
  professionals, without addressing the constraints
  imposed by the conditions in which they practice,
  is unlikely to be a wise use of health care
  resources

Lancaster T et al. Training health care
prfessionals in smoking cessation. Cochrane
Database of Systematic reviews. 14 Nov 05
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Roadblocks to cessation

• Takes time in clinic.
• Inability to order medications unless pt enrolled
  in class
• Getting people info on the class
• Pts fear of gaining weight
• Pts scheduling the class
• Pts completing the class

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We need to change our approach

• Every pt.Every time
• Document tobacco dependence on the problem list
• Referral to tobacco cessation clinic
• 1 800 NO BUTTS

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Physicians need to lead the way

• Multi-disciplinary, physician led clinic
• No referrals necessary, walk-in basis
• Occurs once/week at 1600 in cardiology clinic
• 15-30 minutes of education by different
  specialties

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Physicians need to lead the way

• 10 physicians will see the pts
• Determine motivation to quit
• Brief screening
• Counseling
• AHLTA documentation (template provided)
• Write prescriptions
• Should take no more than 30 minutes (no more than
  10 minutes/pt)

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• Can see significant numbers of pts (30)
• Removes excuses for patients
• Removes excuses for doctors
• Doctors taking charge and setting the example

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PREGNANCY??

• Nicotine replacement therapy
• Use only when non-pharmacologic measures have
  failed, and when benefit outweighs risk
• Bupoprion
• prospective, matched, controlled observational
  study
• Pregnant smokers with bupropion were
  significantly more likely to quit than pregnant
  controls (45 versus 14 percent)

Chan et. Al. Effectiveness of bupropion for
smoking cessation during pregnancy. J Addict Dis
200524(2)19-23
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Cost Effectiveness of Smoking Cessation Programs

• Cost effectiveness of physician counseling
  similar to treatment of mild-to-moderate
  hypertension
• Estimated cost per year of life saved 2,000
  traditional smoking cessation program 50,000
  mammographic screening for breast cancer

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Dealing with nicotine withdrawal..
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• 1100 people will stop smoking today
• Their funeral will be within next 2-3 days

CDC 2000
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Relapse Prevention

• Recognize specific relapse problems by
  identifying a problem that threatens his or her
  abstinence.
• Lack of support for cessation
• Schedule follow-up visits or telephone calls
• Help the patient identify sources of support
• Refer the patient for intense counseling or
  support.
• Negative mood or depression
• Refer patient to a specialist.
• Strong or prolonged withdrawal symptoms
• Consider extending the use of an approved
  pharmacotherapy or adding/combining pharmacologic
  medication to reduce strong withdrawal symptoms.

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Relapse Prevention

• Weight gain
• Increase physical activity discourage strict
  dieting.
• Reassure the patient that some weight gain after
  quitting is common and appears to be
  self-limiting.
• Emphasize the importance of a healthy diet.
• Maintain the patient on pharmacotherapy
• Refer the patient to a specialist or program.
• Flagging motivation/feeling deprived
• Reassure the patient these feelings are common.
• Recommend rewarding activities.
• Evaluate for periodic tobacco use.
• Emphasize that beginning to smoke (even a puff)
  will increase urges and make quitting more
  difficult

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Pharmacotherapy Agents