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Smoking Cessation:

Where Are We Now?

Nancy Rigotti, MD

Director, MGH Tobacco Research and Treatment Center Professor of Medicine, Harvard Medical School

[email protected]

mailto:[email protected]

OVERVIEW

The challenge for treatment: A case

2008 US Public Health Service Clinical Guideline

Newer evidence New ways to use older drugs Safety of varenicline New tobacco products

Treating Tobacco as a Chronic Disease

Take Home Message

Treat Tobacco Use Like a Chronic Disease

It needs long-term management and as much of your attention as

treating hypertension and diabetes

WHY TREATING TOBACCO USE MATTERS

#1 preventable cause of death in the U.S.

> 440,000 deaths/year due to tobacco use

½ of smokers die of a tobacco-related disease



Many people still smoke (19% of US adults)

19% of U.S. adults smoke



Many people still smoke (19% of US adults) Prevalence is higher in those with less education and lower incomes Decline in prevalence has stalled Patterns of tobacco use are changing

22% of U.S. smokers do not smoke every day Smokers smoke fewer cigarettes (mean = 15/day)

↑ in small cigars, roll your own (cheaper)




Cessation reduces mortality

Doll, R. et al. BMJ 2004;328:1519

Effects of stopping smoking on survival

of British doctors 50 year follow-up

at age 25-34 (effect from age 35),



at age 55-64 (effect from age 60)




Cessation reduces mortality

Even after chronic disease develops Post MI: Quitting → 36% ↓ in CVD mortality Even after age 65




Cessation reduces mortality Tobacco treatment works and is one of the most cost-effective actions in health care

A CASE

55 yo man with HTN, BMI 30, depression (stable SSRI)

Smokes 20 cigarettes/day

“I know I should quit, but I’ve tried everything and nothing works.”

Used nicotine patch for 3 days → “I still wanted a cigarette”

Used bupropion for 1 month → “I didn’t want to smoke as much…cut down but couldn’t quit”

“What do you think about the electronic cigarette?”

QUESTIONS

What’s an electronic cigarette?

Has he really tried everything?

What are options for your next step?

QUITTING IN PERSPECTIVE National Health Interview Survey - 2010

52% of smokers try to quit each year

Few succeed long-term (quit for 1 year)

~ 6% succeed without help

25-30% succeed long-term with best treatment

Only 32% of those trying to quit seek help

69% of current smokers want to quit

MMWR November 2011;60:1513

THE CHALLENGE FOR TREATMENT

We have effective treatments, but…

We need better treatments We need to deliver the treatments we have

to more smokers

OVERVIEW





SMOKING CESSATION METHODS 2008 US Public Health Service Guidelines

Effective treatments exist

More is better but brief intervention works

Counseling (individual / group / telephone)

Pharmacotherapy – use combinations

Combination is better than either one alone

PHARMACOTHERAPY 1st Line - 2008 US Public Health Service Guidelines

Nicotine replacement OR Skin patch (OTC) 1.9

Gum (OTC) 1.5

Lozenge (OTC) 2.0 Oral inhaler (Rx) 2.1

Nasal spray (Rx) 2.3

Bupropion SR (Zyban,Wellbutrin SR) 2.0

Varenicline (Chantix) 3.1

OVERVIEW





NICOTINE REPLACEMENT

Goal = reduce nicotine withdrawal

All products about equally effective

FDA approved use Start it on the quit date

Use for 8-12 weeks (max: 6-12 mo)

Do not smoke while using NRT Do not combine NRT products

0

24

68

1012

1416

18

0 10 20 30 40 50 60 70 80 90 100 110 120

Time post administration (min)

Pla

sma

nico

tine

leve

l (ng

/mL)

Cigarette (1-2 mg)

Nasal spray (1 mg)

Gum (4 mg)

Patch (21 mg)

PLASMA NICOTINE LEVELS

Cigarettes vs. Nicotine Replacement Products

NICOTINE REPLACEMENT

Long-acting, slow onset → skin patch

Short-acting, faster onset → oral (gum, lozenge, inhaler)

→ nasal (spray)

Constant nicotine level to avoid withdrawal Simplest to use, best compliance User has no control of dose

User controls dose Nicotine blood levels fluctuate more Requires more training to use properly

ARE COMBINATIONS BETTER? 2 head-to-head randomized trials

Piper, Arch Gen Psychiat 2009; Smith, Arch Int Med 2010

5 drug regimens tested (vs placebo) Monotherapy: Patch, lozenge, bupropion Combos: Patch + lozenge, bupropion + lozenge

Trials in 2 settings Clinical trial (on-site counseling) Primary care clinics (using state quitline)

Results Each drug was better than placebo Combinations > monotherapy No 1 combination was better than the other in

both trials

IS MORE BETTER? 3 Drugs vs 1 Drug Steinberg, Ann Intern Med 2009; 150:447-451

Open label RCT 127 smokers with medical illness Drugs tested

Nicotine patch (10 weeks)

Nicotine patch + lozenge + bupropion (ad lib)

Results

Combination > patch (35 vs 19%, p=.04) at 6 mo Was it more drugs or longer drug treatment?

New Ways to Use Older Drugs

NICOTINE REPLACEMENT (Supported by evidence and USPHS*)

*Combine short- and long-acting forms “Patch plus” regimen

*Treat longer to prevent relapse

Continue patch after a “slip”

Start patch before quit day

“Reduce to quit” (gradual reduction)

BUPROPION SR (Zyban, Wellbutrin SR)

Doubles cessation rate independent of its antidepressant effect

Start 1 week before quit day (150 mg qd→bid) Treat for 3 months (up to 6 mo to avoid relapse) Increases seizure risk (Risk <0.1%) Blunts weight gain temporarily

Acts via CNS dopaminergic pathways

Now a generic drug

VARENICLINE

Partial agonist at α4β2 nicotinic receptor Receptor subtype that mediates nicotine dependence

Dual mechanism of action

Partial agonist Stimulates receptor to treat craving, withdrawal

Antagonist Prevents nicotine from binding to the receptor → Blocks reward, reinforcement of smoking

NH

NN

Varenicline vs bupropion vs placebo CO-Confirmed 4-Wk Continuous Quit Rates - Wks 9–12

OR=3.91*

(95% CI 2.74, 5.59)

OR=1.96* (95% CI 1.42, 2.72)

OR=3.85* (95% CI 2.69, 5.50)

OR=1.89* (95% CI 1.37, 2.61)

100

44.4 44.0

30.0 29.5

17.7 17.7

0

20

40

60

Study I Study II

Res

pons

e R

ate

(%)

Varenicline Zyban Placebo

N=349 N=329 N=344 N=343 N=340 N=340

*p<0.0001 Jorenby et al, JAMA, 2006; Gonzales et al, JAMA, 2006

OR 2.86 (95% CI,1.72, 4.11)

p < 0.001

25

20

15

10

0

Con

tinuo

us A

bstin

ence

(%)

n = 355 n = 359

19.2

7.2

OR: 3.14 (95% CI: 1.93 – 5.11)

p < 0.0001

18.6

5.6

OR 4.04

(95% CI, 2.13, 7.67) p < 0.001

22.4

9.3

Stable CVD 1

n = 692 n = 684

Healthy smokers 3

n = 248 n = 251

COPD 2

Varenicline

Placebo

5

Varenicline efficacy across studies Continuous Abstinence Rates (Weeks 9–52)

1 Rigotti et al, Circulation 2010; 2 Tashkin D et al. Chest 2010. 3 Gonzales et al.; Jorenby et al., JAMA 2006

VARENICLINE vs. NICOTINE PATCH Open label randomized controlled trial

(5 countries, n= 746)

0

10

20

30

40

50

60

Weeks 9-12 Weeks 9-52

Varenicline NRT

Aubin HJ. Thorax 2008

End of treatment OR 1.70 (1.26-2.28)

Continuous abstinence OR 1.40 (0.99-1.99)

26 20

56

43

VARENICLINE COMBINATIONS

2 small pilot studies from Mayo Clinic

Varenicline + NRT Well tolerated in patients in residential treatment

Varenicline + Bupropion (“ChanBan”) Uncontrolled study Well tolerated and higher success rate compared with

previous varenicline studies Randomized controlled trial is in progress

Nicotine & Tobacco Research, 2009

FDA Public Health Advisory July 2009

“Chantix (varenicline) or Zyban (bupropion) has been associated with reports of changes in behavior such as hostility, agitation, depressed mood, and suicidal thoughts or actions.”

“FDA is requiring the manufacturers of both products to add a new Boxed Warning: People who are taking Chantix or Zyban and experience any

serious and unusual changes in mood or behavior or who feel like hurting themselves or someone else should stop taking the medicine and call their healthcare professional right away.

Friends or family members …”

VARENICLINE SAFETY The dilemma

Smokers have an increased risk of suicide.

Stopping smoking produces nicotine withdrawal symptoms (depressed mood, anxiety, and irritability)

When these symptoms occur in a smoker who is stopping smoking on varenicline, did the drug or did quitting smoking cause the symptom?

Case reports cannot answer this question.

Clinical trials of varenicline could. They detected no excess of depression or suicidal thoughts, but these studies did not include patients with mental illness.

VARENICLINE SAFETY Gunnell et al, BMJ 2009

UK General Practice Research Database Population based data: 3.6 million patients in 500 practices Data from electronic medical records

Patients starting smoking medication (9/06 – 5/08) NRT (n=63,265) Bupropion (n=6422) Varenicline (n=10,973)

Outcome: rates of suicide, suicide attempt, suicidal thoughts, and new antidepressant therapy

Results: No evidence of increased risk of suicidal outcomes for varenicline vs NRT, bupropion vs NRT

VARENICLINE SAFETY - CVD Two meta-analyses with different conclusions

Does it ↑risk of serious adverse cardiovascular events?

Singh et al, CMAJ, 2011 1.06% for varenicline vs. 0.82% for placebo Peto OR = 1.7, 95% CI (1.1–2.7) Risk difference = 0.24%

Prochaska et al, BMJ, 2012 0.63% for varenicline vs. 0.47% for placebo MH OR = 1.40, 95% CI (0.82--2.39) Risk difference = 0.27%

Both agree: Absolute risk is very low

VARENICLINE SAFETY Bottom Line

Varenicline may increase risk of psychiatric symptoms in some patients. The potential risk is not yet well defined.

Prescribing any drug requires balancing risks and benefits. - Varenicline is one of the most effective drugs available

to treat tobacco dependence - Continuing to smoke is clearly hazardous

FDA Drug Safety Communication – October 2011

“The Agency continues to believe that the drug’s benefits outweigh the risks.”

OVERVIEW





ELECTRONIC CIGARETTE

How much nicotine does it actually deliver? It should be less harmful cigarettes that burn tobacco, but

is it harmless? Does it help people stop smoking? Will it appeal to youth or undermine no-smoking norms? Status at MGH: Smoking policy prohibits its use

Nicotine + propyline glycol

NEW TOBACCO PRODUCTS Noncombustible tobacco products Electronic cigarettes Dissolvable tablets, strips Snus

Waterpipes (hookah, shisha)

OVERVIEW





TREATING TOBACCO IN THE OFFICE 2008 U.S. Public Health Service Guidelines – 5A’s

Routine advice to quit is effective

Brief counseling is more effective ASK all patients about smoking

ADVISE all smokers to quit

ASSESS smoker’s readiness to quit

ASSIST smokers to quit

ARRANGE follow-up care

THE CHALLENGE

Physicians’ use of 5A model is limited Only 50% of smokers who saw a doctor last year

recall being advised to quit Rates of providing assistance are much lower

Newer model Addressing tobacco use as a team effort Create a system of care Embed it into routine practice flow

5A BRIEF COUNSELING MODEL 2000 U.S. Public Health Service Guidelines

ASK Done by office staff

ADVISE Core physician role

ASSESS

ASSIST Connect to health system or

ARRANGE community resources

A NEWER WAY TO ‘ASSESS’

Don’t ask a if a smoker is ready to quit

Just offer treatment “Quitting smoking can be hard, but there is

good treatment and I can help you. Would you like to try?”

REFERRAL RESOURCES Telephone Quitline

Proactive multisession counseling Convenient, private Free Effective - OR 1.4 (95% CI 1.3-1.6) – Cochrane review

1-800-QUIT NOW

Websites Becomeanex.com Quitnet.com

FAX-REFERRAL SYSTEM

You or staff faxes a referral form to the

Quitline

Quitline calls smoker to offer free counseling and + NRT sample

MEDICATION COVERAGE BY HEALTH INSURERS

Medicaid – all FDA-approved meds! even OTC nicotine gum, patch, lozenge Requires prescription but no prior approval

Private insurance – most cover but may need prior approval

Medicare – depends on specific Plan D

Massachusetts

MA Smoking Prevalence after the Medicaid Prescription Benefit

Annual percentage rate (APR) change for smoking prevalence among MassHealth uninsured adults in Massachusetts aged 18-64. Source: Massachusetts Behavioral Risk Factor Surveillance System, 1998 to 2008

Smoking Prevalence in Massachusetts Adults (18 - 64):MassHealth vs. No Insurance

25.0%

30.0%

35.0%

40.0%

45.0%

7/1/199

9

7/1/200

0

7/1/200

1

7/1/200

2

7/1/200

3

7/1/200

4

7/1/200

5

7/1/200

6

7/1/200

7

7/1/200

8

Smok

ing

Prev

alen

ce (6

-Mon

th A

nnua

l Rol

ling

Ave

rage

)

MassHealth (Point Estimates) No Insurance (Point Estimates)

MassHealth (Model Estimates) No Insurance (Model Estimates)

Over 33,000 MassHealth

smokers quit

26% drop in smoking

prevalence

QUESTIONS

What’s an electronic cigarette?

Has he really tried everything? NRT at adequate dose or in combination

Bupropion + NRT

Varenicline (if psychiatric status stable)

Behavioral support – key to bolster self-confidence

NRT to reduce to quit

What are options for your next step?

Common mistakes in treating smokers

Forgetting to give brief advice to quit every time

Using too little medication for too short a time

Not linking smoker to behavioral support

Forgetting that tobacco use is a chronic condition requiring long-term management

SUMMARY

Treating smoking = chronic disease management

Use combinations Drugs + counseling More than 1 drug

Use the systems being built to help you

Quitline (1-800-QUIT NOW)

Keep trying

New harm reduction products are coming

Take Home Message

Treat Tobacco Use Like a Chronic Disease

It needs long-term management and as much of your attention as

treating hypertension and diabetes

no slide title - primary care tipswhy treating tobacco use matters #1 preventable cause of death in...

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