Smoking Cessation: Where Are We Now? Nancy Rigotti, MD

Smoking Cessation: Where Are We Now? Nancy Rigotti, MD Director, MGH Tobacco Research and Treatment Center Professor of Medicine, Harvard Medical School nrigotti@partners.org

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

WHY TREATING TOBACCO USE MATTERS #1 preventable cause of death in the U.S. Many people still smoke (19% of US adults)

19% of U.S. adults smoke

WHY TREATING TOBACCO USE MATTERS #1 preventable cause of death in the U.S. 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)

WHY TREATING TOBACCO USE MATTERS #1 preventable cause of death in the U.S. Many people still smoke (19% of US adults) Cessation reduces mortality

Effects of stopping smoking on survival of British doctors 50 year follow-up at age 25-34 (effect from age 35), at age 35-44 (effect from age 40), at age 45-54 (effect from age 50), at age 55-64 (effect from age 60) Doll, R. et al. BMJ 2004;328:1519

WHY TREATING TOBACCO USE MATTERS #1 preventable cause of death in the U.S. Many people still smoke (19% of US adults) Cessation reduces mortality Even after chronic disease develops Post MI: Quitting 36% in CVD mortality Even after age 65

WHY TREATING TOBACCO USE MATTERS #1 preventable cause of death in the U.S. Many people still smoke (19% of US adults) 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 69% of current smokers want to quit 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 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

SMOKING CESSATION METHODS 2008 US Public Health Service Guidelines Effective treatments exist Counseling (individual / group / telephone) Pharmacotherapy use combinations Combination is better than either one alone More is better but brief intervention works

PHARMACOTHERAPY 1 st 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

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

PLASMA NICOTINE LEVELS Cigarettes vs. Nicotine Replacement Products Plasma nicotine level (ng/ml) 18 16 14 12 10 8 6 4 2 0 0 10 20 30 40 50 60 70 80 90 100 110 120 Cigarette (1-2 mg) Nasal spray (1 mg) Gum (4 mg) Patch (21 mg) Time post administration (min)

NICOTINE REPLACEMENT Long-acting, slow onset skin patch Constant nicotine level to avoid withdrawal Simplest to use, best compliance User has no control of dose Short-acting, faster onset oral (gum, lozenge, inhaler) nasal (spray) 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) Acts via CNS dopaminergic pathways Doubles cessation rate independent of its antidepressant effect Now a generic drug 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

NH VARENICLINE N N 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

Varenicline vs bupropion vs placebo CO-Confirmed 4-Wk Continuous Quit Rates - Wks 9 12 Response Rate (%) 100 60 40 20 OR=3.91 * (95% CI 2.74, 5.59) OR=1.96 * (95% CI 1.42, 2.72) 44.4 44.0 29.5 17.7 OR=3.85 * (95% CI 2.69, 5.50) OR=1.89 * (95% CI 1.37, 2.61) 30.0 17.7 0 N=349 N=329 N=344 N=343 N=340 N=340 Study I Study II Varenicline Zyban Placebo * p<0.0001 Jorenby et al, JAMA, 2006; Gonzales et al, JAMA, 2006

Varenicline efficacy across studies Continuous Abstinence Rates (Weeks 9 52) 25 OR: 3.14 (95% CI: 1.93 5.11) p < 0.0001 OR 4.04 (95% CI, 2.13, 7.67) p < 0.001 OR 2.86 (95% CI,1.72, 4.11) p < 0.001 22.4 Varenicline Continuous Abstinence (%) 20 15 10 5 19.2 7.2 18.6 5.6 9.3 Placebo 0 n = 355 n = 359 n = 248 n = 251 n = 692 n = 684 Stable CVD 1 COPD 2 Healthy smokers 3 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) Varenicline NRT 60 50 40 30 56 43 20 10 26 20 0 Aubin HJ. Thorax 2008 Weeks 9-12 Weeks 9-52 End of treatment OR 1.70 (1.26-2.28) Continuous abstinence OR 1.40 (0.99-1.99)

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.

ELECTRONIC CIGARETTE Nicotine + propyline glycol 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

NEW TOBACCO PRODUCTS Noncombustible tobacco products Electronic cigarettes Dissolvable tablets, strips Snus Waterpipes (hookah, shisha)

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 ADVISE ASSESS ASSIST ARRANGE all patients about smoking all smokers to quit smoker s readiness to quit smokers to quit 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 ADVISE ASSESS ASSIST ARRANGE Done by office staff Core physician role Connect to health system or 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 Massachusetts 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

MA Smoking Prevalence after the Medicaid Prescription Benefit Smoking Prevalence (6-Month Annual Rolling Average) 45.0% 40.0% 35.0% 30.0% 25.0% Smoking Prevalence in Massachusetts Adults (18-64): 7/1/1999 7/1/2000 MassHealth vs. No Insurance 7/1/2001 26% drop in smoking prevalence 7/1/2002 7/1/2003 7/1/2004 7/1/2005 7/1/2006 Over 33,000 MassHealth smokers quit 7/1/2007 7/1/2008 MassHealth (Point Estimates) MassHealth (Model Estimates) No Insurance (Point Estimates) No Insurance (Model Estimates) 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

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 Keep trying Quitline (1-800-QUIT NOW) 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