Treating Tobacco Use in Patients with Cardiovascular Disease

Transcription

1 Treating Tobacco Use in Patients with Cardiovascular Disease Nancy Rigotti, MD Professor of Medicine, Harvard Medical School Director, Tobacco Research & Treatment Center, Associate Chief, General Medicine Division, Massachusetts General Hospital, Boston, MA, USA

2 OVERVIEW Benefits and challenges in treating smokers with cardiovascular disease (CVD) Current guidelines for treating all smokers Special issues for CVD Efficacy and safety of drugs Hospitalization Second hand smoke and CVD patients

3 SPECIAL ISSUES FOR TREATING SMOKERS WITH CVD CVD is a special opportunity Risk of CV events and death is rapidly reversible 1 st CV event is a powerful stimulus for change Patients with CVD are often in the hospital CVD is a special challenge Smokers who do not quit after 1 st diagnosis are difficult to treat Depression is a common Safety of pharmacotherapy in CVD

4 OVERVIEW Benefits and challenges in treating smokers with cardiovascular disease (CVD) Current guidelines for treating all smokers Special issues for CVD Efficacy and safety of drugs Hospitalization Second hand smoke and CVD patients

5 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

6 PHARMACOTHERAPY 1 st Line US Public Health Service Guidelines Nicotine replacement OR Skin patch 1.9 Gum 1.5 Lozenge 2.0 Oral inhaler 2.1 Nasal spray 2.3 Bupropion SR (Zyban,Wellbutrin SR) 2.0 Varenicline (Champix) 3.1

7 NICOTINE REPLACEMENT Efficacy in Cardiovascular Disease Little evidence in smokers with CVD 3 trials of nicotine patch in stable CVD (1990s)* All showed efficacy in short term (up to 14 wks) Only 1 followed patients for >14 weeks It showed no benefit at 6 and 12 months * US Surgeon general s report, 2010

8 NICOTINE REPLACEMENT Safety in Cardiovascular Disease Safe in stable CVD Uncertainty about unstable CVD Severe or unstable angina Acute coronary syndrome Recent MI (within 2 weeks)

9 SAFETY OF NICOTINE REPLACMENT CVD Pathophysiology: Smoking- related Mechanisms Caused by Nicotine? HR, BP ( sympathetic tone) + Vasoconstriction + Platelet activation, thrombosis Endolethial injury, inflammation (?) O 2 delivery (CO) Strength of hemodynamic effect of nicotine is related to its rate of delivery (cigarette >> nasal spray > patch)

10 BUPROPION SR (Zyban, Wellbutrin SR) Doubles cessation rate independent of its antidepressant effect Reduces post-cessation weight gain temporarily Stable CVD: Effective and safe Tonstad, 2003 Acute CVD: Safe but only efficacy borderline Rigotti 2006

11 NH VARENICLINE N N Binds selectively to α4β2 nicotinic receptor 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

12 Varenicline vs bupropion vs placebo CO-Confirmed 4-Wk Continuous Quit Rates - Wks 9 12 Response Rate (%) 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) N=349 N=329 N=344 N=343 N=340 N=340 Study I Study II Varenicline Zyban Placebo * p< Jorenby et al, Gonzales et al, JAMA, July 5, 2006

13 VARENICLINE vs. NICOTINE PATCH Open label randomized controlled trial (5 countries, n= 746) Varenicline NRT Aubin HJ. Thorax Weeks 9-12 Weeks 9-52 End of treatment OR 1.70 ( ) Continuous abstinence OR 1.40 ( )

14 Varenicline CVD Study Participants (n=714) Smoke 10 cigarettes/day Stable cardiovascular disease (CVD) Cardiac disease (angina, prior MI, CABG, or PTCA) Peripheral vascular disease Cerebrovascular disease (prior stroke or TIA) Exclusion criteria New diagnosis of CVD in past 2 months CVD instability or CVD procedure in past 2 months Psychiatric disorders Depression diagnosis or treatment with antidepressants (past yr) History of psychosis, panic disorder, or bipolar disorder

15 Efficacy Continuous Tobacco Abstinence OR: 6.11 (95% CI: ) p < Varenicline (n = 355) Placebo (n = 359) Continuous Abstinence (%) OR: 3.92 (95% CI: ) p < OR: 3.14 (95% CI: ) p < Weeks 9 12 (Primary Endpoint) OR = Odds ratio; CI = 95% Confidence intervals Weeks 9 24 Weeks 9 52 (Key Secondary Endpoint)

16 Efficacy 7-day Point Prevalence Tobacco Abstinence Abstinence Point Prevalence (%) Drug Treatment * * 18.1 Follow-up Varenicline (n = 355) Placebo (n = 359) Week * Week 12 OR: % CI: p < Week 24 OR: % CI: p < Week 52 OR: % CI: p < OR = Odds ratio CI = Confidence interval

17 Safety Adjudicated Deaths and Cardiovascular Events* Number of Participants Varenicline (n = 353) Placebo (n = 350) n % n % Deaths - all causes Cardiovascular deaths Non cardiovascular deaths Any adjudicated cardiovascular event* Coronary artery disease Non-fatal MI Need for coronary revascularization Hospitalization for angina pectoris Hospitalization for congestive heart failure Cerebrovascular disease Non fatal stroke Transient ischemic attack Peripheral vascular disease (PVD) New diagnosis or admission for procedure to treat *Reported or observed CV events and all deaths were reviewed separately and adjudicated by an independent event committee blinded to study arm

18 VARENICLINE SAFETY in CVD Meta-analysis (Singh et al, CMAJ 2011) Meta-analysis of 14 RCTs of varenicline vs. placebo Risk of serious adverse cardiovascular events 1.06% for varenicline vs. 0.82% for placebo Peto OR = 1.7, 95% CI ( ) Risk difference = 0.24% Is it a true result? Much discussion about methods FDA is doing a separate meta-analysis If real, the absolute risk is low Less than continuing to smoke? - YES Less than quitting using a different med?

19 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 to the product label

20 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 detected no excess of depression or suicidal thoughts, but these studies did not include patients with mental illness.

21 VARENICLINE SAFETY Cohort study (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

22 VARENICLINE SAFETY New FDA Analaysis (October 2011) Analyses of 2 databases of patients Veterans Hospitals Department of Defense Data from electronic medical records Patients starting smoking medication NRT Varenicline Outcome: rates of hospitalization for psychiatric diagnosis Results: No difference between varenicline and NRT

23 VARENICLINE SAFETY My Bottom Line Varenicline may increase risk of psychiatric symptoms in some patients. The potential risk is not yet well defined. Prescribing varenicline, like 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 In most cases, the benefits of varenicline outweigh the risks but take care and follow up

24 COMBINATIONS OF DRUGS 2 head-to-head randomized controlled 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 > single drugs No 1 combination was better in both trials

25 HOSPITALIZED SMOKERS Hospitalization as a window of opportunity Smoke-free hospitals require temporary abstinence from tobacco use Illness motivates smokers to try to quit Interventions can help them to succeed What is the evidence?

26 SMOKING INTERVENTIONS FOR HOSPITALIZED SMOKERS: Meta-analysis (Rigotti NA, Munafo MR, Stead L. Cochrane Library 2007; Arch Int Med 2008) Bedside counseling followed by telephone support for at least one month after discharge increases the odds of smoking cessation by 65% It is effective regardless of the reason for admission It is not effective without continued support after discharge

27 MGH SYSTEM for Inpatients Step 1: Identify smoking status at admission Step 2: Brief advice by care team (RN, MD) Step 3: Smoking counselor visit

28 MGH SYSTEM for Inpatients Step 1: Identify smoking status at admission On doctors and nurses electronic admission order set Generates electronic list of smokers for the Tobacco Treatment Service

29 MGH SYSTEM for Inpatients Step 1: Identify smoking status at admission in an electronic database Step 2: Care team - quit advice, NRT order Booklet put on every bed by housekeeping

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32 MGH SYSTEM for Inpatients Step 1: Identify smoking status at admission in an electronic database Step 2: Care team - quit advice, NRT order Booklet put on every bed by housekeeping Step 3: Smoking counselor visit Assess nicotine withdrawal relief Assess interest in quitting Assist to make a quit plan for discharge Arrange post discharge care (Refer to Quitline, recommend discharge med)

33 SMOKING CESSATION OUTCOMES January- June 2007 (n=553) Outcome All Patients (ITT) Quit for past week 2 weeks after discharge 24% 3 months after discharge 18%

34 INPATIENT OUTPATIENT TRANSITION Ensure counseling support after discharge Interactive voice response (IVR) system to identify smokers who want / need counseling Increase use of medication after discharge Offer free sample at discharge to remove barrier to starting immediately

35 Sample of IVR Script - Day 14 call Are you trying to stop sm oking at this tim e? Have you sm oked a cigarette in the last 7 days? Yes D on t give up. Quitting isn t easy, but if you keep trying and get som e help you can quit sm oking. W e recom m end you talk to a tobacco counselor. No Great! How confident are you that you w ould be able to stay quit for the next m onth? Low It sounds like your confidence is a little low. W e recom m end you talk to our tobacco counselor to help you stay on track. High Great! It sounds like you are doing w ell! A counselor calls every smoker who requests a call

36 Helping HAND Study Improving tobacco treatment delivery after discharge (RC1 HL099668) 330 Smokers Admitted to MGH Randomize Standard Care N=165 Extended Care* N=165 Outcomes assessed at 1 and 6-month follow-up Tobacco abstinence at 6 months (biochemically validated) Tobacco abstinence at 1 month Use of tobacco treatment (counseling or medication) Cost effectiveness (cost/quit) * Extended Care = 5 IVR calls over 3 months with counselor call-back option + 30 days of free medication of patient s choice in hand at discharge

37 OVERVIEW Benefits and challenges in treating smokers with cardiovascular disease (CVD) Current guidelines for treating all smokers Special issues for CVD Efficacy and safety of drugs Hospitalization Second hand smoke and CVD patients

38 NONSMOKERS WITH CVD Smoke-free laws 20% fewer acute MI hospital admisions Nonsmokers who are exposed to SHS after hospitalization for acute coronary syndrome are more likely to need readmission in the next year We do not ask patients about SHS exposure A hospitalization might be a good time to encourage the patient and family to make the home and car smoke-free

39 SURVEY OF HOSPITALIZED NONSMOKERS WITH CVD (n=214) 25% of hospitalized nonsmokers with CHD had SHS exposure in the home, car, or at work in the past 30 days Household smokers were spouses or an adult child living at home Nearly half of nonsmokers with CHD were unaware of the cardiac risk of SHS Health care providers rarely addressed SHS exposure risk (17% asked about SHS, 1% advised a smokefree home)

40 For the sake of my heart and yours This is a Smoke Free Home Put This Friendly Reminder in a Place Where Everyone Can See It! A Smoke Free Home and Car Matter if you have Heart Disease Breathing in someone else s cigarette smoke can cause - and worsen - heart disease in a nonsmoker. Breathing in even a little smoke raises your chance of having a heart attack. Home and car are the main places where nonsmokers contact cigarette smoke. The only safe amount of How to Protect Yourself Make a firm rule that no one smokes in your home or car ever! Put up this sign to let everyone know. Ask people around you not to smoke for the sake of your heart. Stay away from places where smoking is allowed. An Important Message for the Smokers in Your Life Protect your family Make your home and car smoke- free. Try to stop smoking to help you and your loved ones. For help: ocall QUIT-NOW (Free Smokers Quitline) ogo to Becomeanex.or

41 Por el bien de mi corazón y el suyo Este es un Hogar Libre de Humo Ponga este recordatorio agradable en un lugar donde todos pueden verlo Un Hogar y Un Automóvil Libre de Humo Importa Si Usted Tiene Problemas Cardíacos Respirar el humo del cigarrillo de otra personapuede hacer - y empeorar - la enfermedadcardíaca en los que no fuman. Respirar humo aunque sea un poco aumenta la probabilidad de tener un ataque al corazón. Su hogar y coche son los lugares principales en donde los que no fuman tienen la mayoría del contacto con humo del cigarillo. La única cantidad segura de humo de segunda mano es NINGUNA. Cómo protegerse a sí mismos Haga una regla firme de que nadie fume en su casa o automóvil - nunca! Ponga este letrero para que todos lo sepan. Pidale a las personas que lo rodean no fumar por el bien de su corazón. Manténgase alejado de los lugares donde se permite fumar. Un mensaje importante para los fumadores en su vida Proteja a su familia. -Haga de su hogar y automóvil libre de humo. -Trate de dejar de fumar para ayudarse a usted y a sus seres queridos. Para obtener ayuda: Llame al DEJALO ( ) (Linea gratis para los que no fuman) Visite la pagina de internet: rg/

42 TAKE HOME POINTS Addressing tobacco use is essential for the management of patients with CVD Pharmacotherapy for smoking cessation appears to be safe in CVD patients Starting treatment in the hospital improves quit rates after discharge Advise nonsmokers to keep the home smoke-free Your advice and assistance makes a difference!

43 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 hyperlipidemia