Allan Prochazka, M.D., M.Sc. F.A.C.P. Professor of Medicine University of Colorado School of Medicine Asst. Chief, Research Ambulatory Care Denver VAMC Case Smoking and cessation in the hospitalized patient Using the 5A s in the hospitalized patient Practical use of drug therapy for cessation Co-Investigator on VA Health Services Research Grant Improving the delivery of smoking cessation guidelines in hospitalized veterans
56 yo man admitted for pancreatitis PMH: HTN, Type II DM, DJD, ETOH Social: 20-25 cigarettes per day since age 16, Marlboro, several brief prior quit attempts, last year took a couple varenicline tablets from a friend and said it made cigarettes taste bad, tried nicotine patch 14 mg for a few days in 2006 without much success Day 2, pain is improving, pt is starting to take clear liquids and is complaining to the nurses about the smoking restrictions in your hospital. After lunch he tried to leave the ward with his IVAC to get outside to smoke What to do now? 1. Is it safe to prescribe medications to control withdrawal symptoms in hospitalized patients? Yes No Not sure
2. Which is the best choice to control withdrawal symptoms in this patient? Buspirone 5 mg daily Nicotine lozenge 2 mg q 1-2 hr as needed Bupropion 300 mg daily Nicotine patch 21 mg daily Nicotine patch 14 mg daily The patient is ready for discharge, how long should one typically continue antismoking medications? 1-2 weeks 3-4 weeks 4-6 weeks 8-12 weeks 24 weeks
CDC, National Health Interview Survey CDC Cessation Fact Sheet, 2010 Smoking in Hospitalized Patients Current rates of smoking among hospitalized medical patients On VA wards, about 30% Cook County, 36% 1 Hospitalized patients often suffer from withdrawal symptoms and may smoke while admitted Survey from Boston 2 1 Katz A, et al. J Hosp Med 2008;3:369-375 2 Rigotti NA, et al, Prev Med 2000;31:159-166
Unpublished VA Pilot Data COPD patients admitted for exacerbations 48% received smoking cessation counseling 1 1 Yip NH, et al. COPD 2010;7:85-92 Many smokers are hospitalized for conditions related to their habit Smokers may have low awareness (or denial) about the relationship between their medical conditions and tobacco (e.g. peripheral vascular disease) About 40% in a Boston study indicated they are ready to quit in the next 30 days 1 At Denver Health, 20% indicated they had already taken action to quit 2 and at 20 months f/u, 18% had quit 3 Cardiology pts in Chicago, 15% smoked and 75% said they were ready to quit 4 1 Rigotti NA, et al. Am J Prev Med 1999;17:255-259 2 Vernon JD et al. Prev Med 1999;28:488-495 3 MacKenzie TD, et al. Prev Med 2004;39:1087-1092 4 Shah LM, et al. J Hosp Med 2010;5:26-32 Acute Coronary Syndrome 420 smokers in Greece 1, 40% quit at one year Of those who attended a cessation program after hospital discharge, 48% quit 136 Smokers in Michigan (23% of those enrolled) 48% quit after discharge and stayed quit for up to 1 year 2 CABG 146 smokers underwent CABG 93% quit at 3 months post surgery 3 Veterans (n=354) 15% quit at 6 months post discharge Those who didn t smoke during the admission, 2.7 X higher odds of being quit at 6 months 4 1 Vogiatzis I, et al. Hellenic J Card 2010;51:294-300 2 Holtrop JS et al. J Hosp Med 2009;4:E3-E9 3. Pietroban RC, Barbisian JN. Rev Bras Circ Cardiovasc 2010;25:79-84 4 Duffy SA, et al. Prev Med 2010;50:285-287
Surveys suggest that we generally are treating withdrawal in the hospital and don t focus on enhancing long term cessation NRT (nicotine replacement) twice as likely to be given to a pt experiencing withdrawal than to other smokers 1 Take advantage of the teachable moment and help patients with cessation Recent guidelines based on systematic review of 3000 trials concluded 2 : Physician counseling is effective Quitlines are effective Virtually all smokers can benefit from drug therapy to help with quitting, not just those who are highly dependent So, switch the focus from short term withdrawal control to developing a cessation plan 1 Rigotti NA, et al. Am J Prev Med 1999;17:255-259 2 Treating Tobacco Use and Dependence: 2008 Update, USDHHS, Public Health Service Cochrane Systematic Review of Trials 1 All trials including smokers and recent quitters (< 1 month) Intervention started in the hospital Followup of at least 6 months 29 trials found with 15,000 participants Wide variety of designs and moderate heterogeneity in the results 1 Rigotti NA, et al. Cochrane Database of Systematic Reviews, 2007 Brief Hospital Advice > 15 minutes in Hospital Advice Hospital Advice + Short f/u 6 Month Cessation Outcomes by Intensity of Counseling # Studies # Subjects OR 95% CI 1 1351 1.16 0.8-1.67 8 3617 1.08 0.89-1.29 6 4476 1.09 0.91-1.30 Hospital Advice + More than 1 month f/u support 17 5608 1.65 1.44-1.90 Overall 29 15052
Study Intervention Control OR 95% CI Campbell 1991 Campbell 1996 21/107 21/105 0.98 0.5-1.9 8/30 3/32 3.52 0.8-1.5 Lewis 1998 4/62 6/62 0.64 0.2-2.4 Molyneux 2003 NRT vs Placebo or no NRT 10/91 4/91 2.69 0.8-8.9 Vial 2002 9/42 1/22 5.73 0.7-48 Overall 52/332 35/312 1.47 0.9-2.4 Bupropion vs Placebo Study Intervention Control OR 95% CI Rigotti 2006 25/124 17/122 1.56 0.8-3.1 Brief advice in the hospital is not enough to achieve long term cessation Linking hospital based advice with outpatient followup clearly works, the more the better Addition of nicotine replacement therapy is probably helpful, but not enough data to say definitively. Minimal toxicity Suggestion of benefit from bupropion, but only one study Ask Advise Assess Assist Arrange
Ottawa Model 1,2 Implemented the 5A s across all providers in 9 hospitals Trained staff Templates/pathways for each step Continuous abstinence rates at 6 months 29% vs 18% with usual care (p=0.02) 1. Reid RD, et al. Nicotine Tob Res 2010;12:11-18 2. www.ottawamodel.ca (accessed 9/14/10) Ask all patients 18 and older whether they smoke. Grade A recommendation USPSTF 1 Makes smoking salient for patients and providers Triggers quit attempts by patients and advice/ interventions by providers Electronic medical records can make this easier 2 Training nurses to ask routinely as part of their admission evaluation increased asking and advising from 57% to 86% of admissions 3 Remember that patients may have quit during the prodrome of their illness, they are still smokers until they actively work towards quitting 1 US Preventive Services Task Force. Ann Intern Med 2009;150:551-555 2 Linder JA, et al. An electronic health record based intervention to improve tobacco treatment in primary care. Arch Intern Med 2009;169:781-787 3 Duffy SA, et al. J Gen Intern Med 2010;25 Suppl 1:3-10. Strongest data in general are for physician advice Other clinicians also likely to be effective Systematic review showed that brief advice alone is probably not enough for many hospitalized smokers Ideal to have a consistent approach across providers to reinforce the message Patients will receive advice from multiple sources Best to avoid preaching/nagging, stay friendly and positive about the possibilities for change Remind patient that relapse often occurs with a short time after discharge and we can help prevent that Baxter S, et al. Nicotine Tob Res 2010;(epub 5/14/10)
Clear: I think it s important for you to quit smoking now and I can help you. Strong: As your doctor, I need you to know that quitting smoking is the best thing you can do for your health. Your care team and I will help you. Personalized: Smoking robs your body of oxygen and limits your breathing, quitting will greatly improve how far you can walk. Don t try to force cessation on the patient Reinforce that help is available when they are ready Many times these patients will surprise you and either quit on their own or be ready to quit at a future visit to their PCP Identify willingness to quit Are you willing to give quitting a try? You ve been forced to fast from smoking in the hospital, have you thought about quitting for good? If yes, can we start now. Are you having problems with being off cigarettes? If ready now, then consider drug therapy while in the hospital If not ready, then work on motivation and on barriers
Identify the barriers Fear of weight gain Worry about urges Too much stress, etc. Now is a great time to quit, you have already gone xx days without smoking Give tailored information about benefits of quitting, risks of smoking, availability of treatment E.g. We can use medication to take the edge off urges after quitting. Identify Tobacco Dependence DSM IV R criteria Withdrawal with cessation Smoking in the face of medical illness Fagerstrom How soon after awakening do you smoke your first cigarette? If < 5 minutes, then highly dependent Behavioral key is to to start in the hospital and link to the outpatient setting Drug Therapy Smokers wanting to quit need both in most cases Dose of each one can be tailored to the patient s needs and availability of help
Key element is time with patient and empathic counselor More time, more benefit e.g. NRT or bupropion plus 2 phone calls 23% cessation at 24 months in an outpatient setting Ellerbeck EF, et al. Effect of varying levels of disease management on smoking cessation. Ann Intern Med 2009;150:437-446. Practical Recommendations for patients Tell family, friends, coworkers Make the home smoke free when you go home Start acting like a non-smoker Identify barriers to cessation Remove tobacco products from environment Review prior quit attempts, learn from them Anticipate triggers and challenges Encourage others in the home to quit Provide a supportive clinical environment (e.g. We can help you if you are having problems ) Provide options Referral not always available Quitlines are proven to increase success rates in outpatients, available in most states and are free Mottillo S, et al. Behavioural interventions for smoking cessation: a meta-analysis of RCT s. Eur Heart J 2009;30:718-730. Lichtenstein E, et al. Amer Psychol 2010;65:252-261 Self-help materials All forms of approved drug therapy would be possible in principle for a hospitalized patient, but there are sparse data Select based on potential side effects, time to action, nursing considerations, prior patient experience and preferences FDA Approved Agents for Smoking Cessation Nicotine Replacement (NRT) Bupropion Varenicline
Most commonly used therapy in studies of hospitalized patient smoking cessation Need to avoid in patients with ACS Dose Forms Frequent Dosing (i.e. q 1-2 hrs prn) Gum Lozenge Inhaler Nasal Nicotine Daily Dosing Patch Daily dosing easier to administer in a hospitalized patient than ad lib or prn dosing Overall success rate comparable among the products Odds ratios for quitting: Patch 1.66; Gum 1.43; Lozenge 2.00; Inhaler 1.90; Nasal Spray 2.02 Doubles the quit rate (e.g. 5-8% to 10-15%) compared to advice (e.g. 10% to 17%) compared to placebo, overall odds ratio 1.58 (based on 40,000 patients studied, 132 trials) L Stead et al, NRT for Smoking Cessation, Cochrane Review, 2008 Selection based on side effects, patient preference, insurance coverage PDR duration of therapy 8-12 weeks Selected patients need longer therapy or higher doses Schnoll RA et al. Effectiveness of extended duration transdermal nicotine therapy:a randomized trial. Ann Intern Med 2010;152:144-151 3 strengths (21, 14, 7 mg/24hr) Onset of action is within hours, steady state in days Some patients require higher doses (e.g. very heavy smokers), but for typical pack a day smoker 21mg is the starting dose In the hospitalized patient would hold on higher dose therapy until after discharge 4-6 weeks on 21 mg, 2-4 weeks on 14 mg, then 2-4 weeks on 7 mg Costs $25-40 per 14 day supply Side Effects Skin irritation (30%) Skin allergy (1-4%) Poor sleep/nightmares (10%) Arm pain (2-4%)
2 forms (2 mg and 4mg), 4 mg best for most smokers Available OTC and in generic forms and in various flavors Absorption is buccal, so park and chew Regular dosing better than ad lib Typical patient will use 5-8 pieces per day Retail cost $35-50 for 108 pieces Side Effects Dental trauma, jaw pain, nausea, upset stomach Duration of Use 8-12 weeks 2-5% have trouble quitting gum Long term use combined with behavioral therapy (up to 5 years) safe and effective, 25% validated quit rate in Lung Health Study Available OTC, 2 mg and 4 mg Allow lozenge to slowly dissolve, no chewing or swallowing of the lozenge need to be careful not to develop too much saliva 20-30 minutes per lozenge Dose 20 max per day Side effects: hiccups, nausea, stomach upset, palpitations Cost $30-40.00 for box of 72 lozenges Very rapid absorption of nicotine Useful in the heavily dependent smoker because high levels are achieved in a few minutes Dosing 0.5 mg per spray, one spray in each nostril is one dose (about the amount of nicotine in one cigarette) Typical patient uses 3-6 doses per day Side Effects: mostly irritation, face pain, perhaps more likely to result in difficulty stopping use due to fast absorption Costs $45-50 per 10 ml vial (100 doses)
Each cartridge 10 mg nicotine, 4 mg released, 2 mg absorbed Best with continuous puffing (80 deep inhalations over 20 minutes give 2 mg nicotine, about the same as one cigarette) Dosage 6-16 cartridges per day Side Effects: mouth/nose irritation Costs up to $160 per 168 cartridges (about 2-4 weeks supply) Has been tested in many trials (however, not in the hospital setting), so reserve for the patient once stable and home Higher dose patches not better when given as a routine for all smokers, best to titrate by intake/level of dependence Useful for the very heavy smoker Safety in trials and practice has been good Nicotine patch+nicotine gum or lozenge Higher quit rate than either alone Allows for steady level with ad lib gum Cochrane review (6 trials of high dose or combo therapy) odds ratio for quitting 1.21 (95% CI 1.03-1.42) compared to monotherapy Primary care trial found that cessation rate with patch/lozenge was 27% at 6 months compared to 18% with patch alone Smith SS, et al. Arch Intern Med 2009;169:2148-2155 Main limitation is the cost of the therapy In the pt who has cut down recently, should generally dose based on their long term use level Ad lib meds with frequent dosing (e.g. gum, lozenge, inhaler, nasal spray) are hard to implement in a hospital environment Nicotine patch is the simplest from a dosing/ nursing perspective When person goes home, can switch to the mode of delivery and dosing regimen that fits best for the patient
Works in normal, non-depressed smokers Relatively slow onset of action (7-10 days) SA form is only type approved for cessation Dosage: 150 mg a day for 3 days, then 150 mg bid, but not much difference in effectiveness between 150 and 300 mg /day Only one trial on use in hospitalized patients, trend towards effect but not significant Duration: 3 months, but longer term therapy is safe and effective in outpatients Minimal cardiovascular effects when given alone $70/month for generic long acting bupropion Side Effects Common Shaky,tremor Headache Dry mouth Rare but serious Seizures Avoid in those with epilepsy, active drug use, concomitant psychiatric medications, bulemia, MAOI use Rare, not a large problem Worsened HTN when combined with NRT Allergic reactions (hives, angioedema) Overall odds ratio for cessation 1.94 (95% CI 1.72 to 2.19) based on 19 trials Hughes JR et al, Cochrane Review 2007 Combination Therapy (patch+oral inhaler+bupropion) can work well with quit rates at 26 weeks 35% compared to 19% with patch alone and acceptable side effects Steinberg MB, et al. Triple Combination pharmacotherapy for medically ill smokers. Ann Intern Med 2009;150:447-454. Combined with lozenge, 30% 6 month quit rate Smith SS, et al. Comparative effectiveness of 5 smoking cessation pharmacotherapies in primary care clinics. Arch Intern Med 2009;169:2148-2155 Less weight gain than with patch
Very useful Healthy populations (e.g. worksite) Active cardiac disease Harder to use in some patient groups Psychiatric comorbidity Substance Abuse Will work in the hospital setting, but probably won t kick in quickly enough to help the person with severe withdrawal symptoms Bottom Line: very useful agent overall, limited info on use in the hospital, but may be a good choice in the cardiac patient, main issue is caution with regard to seizure risk First designer drug for tobacco dependence 1 A derivative of cytisine, derived from the golden rain tree Hasn t really been a clinical reason to know about central nicotine receptors before this, but interactions with the α4β2 receptor are the main mechanism of action Acts as a partial agonist causing dopamine release, also is an antagonist and blocks the binding of exogenous nicotine 1. Hays JT, Ebbert JO, NEJM 2008;359:2018-2024 Varenicline Cessation Efficacy at 24 Wks 1 1. Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD006103
Copyright restrictions may apply. Treatment-Emergent Adverse Events (Including Those Not Necessarily Related to Study Drug)* Gonzales, D. et al. JAMA 2006;296:47-55. 714 smokers, stable CVD (hx MI, Revasc, Angina, PVD, Cerebrovascular) Excluded recent procedure or unstable CAD, uncontrolled HTN, severe CHF, severe COPD, liver, GI, Diabetes (A1c >9), psych or recent psych tx, drug use 1. Rigotti NA, et al. Circulation 2010;121:221-229 Tobacco CARs Rigotti, N. A. et al. Circulation 2010;121:221-229 Copyright 2010 American Heart Association
Varenicline effective compared to placebo with at least a doubling of the quit rate OR 2.33 (95% CI 1.95-2.88) Cahill C. Cochrane Review, 2008 Moderately (OR 1.52, 95% CI 1.22-1.88) better quit rate than bupropion SA Perhaps better than NRT (OR 1.33 (1.01-1.71), but few trials Nausea was the most predominant side effect Rate of drug discontinuation was relatively low In approval RCT s 2 cases of psychosis Numerous case reports since approval Worsening of schizophrenia 5 days after starting varenicline in patient who was stable on low dose neuroleptic Mania requiring hospitalization 1 week after starting varenicline in a bipolar patient who was stable on valproate Am J Psych 2007;164:1269-1270 UK 2682 pts in general practice 2 cases of attempted suicide Mood change/depression 1.7% Anxiety 1.2% Kasliwsal, et al. Drug Safety 2009;32:499-507. VA PBM July 2009, 149 cases of suicidal behaviors out of approximately 100,000 patients treated VA Bulletin, July 2, 2009
Market Share Varenicline Bupropion Varenicline Bupropion# Nicotine Control* 13% 7% 77% n/a Suicides 22 6 0 0 Attempts 46 6 1 0 Ideation 377 104 2 1 Agression 172 131 8 22 Moore TJ, Furburg CD, BMJ 2009;339:1272-1273 # all indications * Amoxicillin July 2009 Watch for changes in behavior, hostility, agitation, depressed mood, suicidal thinking and behavior Stop the meds if above occur and monitor until resolved Rates of suicide and depression are low (less than 1/1000), but warrants caution with both drugs in patients with psychiatric disorders and also means that both should be prescribed only with adequate followup Expensive ($370 for 168 1 mg tabs, enough for 12 weeks) No data on use in hospital setting, so wouldn t recommend starting it there Best to save for those who have failed first line therapies once they have gone home VA Guidelines Second line agent Avoid in patients with psychiatric disorders unless working collaboratively with mental health provider Monitor after starting therapy on regular basis
Link the patient to the Colorado Quitline Make sure that the PCP knows that an active quit attempt has been started If your hospital does post-discharge calls to patients, consider adding smoking status to the questions Smoking remains a problem in hospitalized patients 5 A s approach works Consider expanding the use of drug therapy beyond those who have acute withdrawal Link patient to outpatient resources to support the quit attempt