Online Table 1. Site Investigators, and Members of the Steering Committee, Data Safety
Monitoring Board, and Endpoints Evaluation Committee.
Site Investigators
Canada: Thao Huynh, McGill University Health Centre (MUHC), Montréal, QC; Claude
Lauzon, Centre de santé et de services sociaux de la Région de Thetford, Thetford, QC; Jean
G. Diodati, Hôpital du Sacré-Coeur de Montréal, Montréal, QC; Peter Klinke, Victoria Heart
Institute, Victoria, BC; François Grondin, Hôtel-Dieu de Lévis, Lévis, QC; Andreas
Wielgosz, University of Ottawa Heart Institute, Ottawa, ON; Sat Sharma, St. Boniface
General Hospital, Winnipeg, MB; Niels Schwarz, Nanaimo Regional General Hospital,
Nanaimo, BC; Stéphane Rinfret, Centre Hospitalier de l’Université de Montréal (CHUM)
Notre-Dame Hospital, Quebec, QC; Howard Wightman, Valley Regional Hospital,
Kentville, NS; Sohrab Lutchmedial, New Brunswick Heart Centre, Saint John, NB; JeanPierre Picard, Hôtel-Dieu de Sorel, Sorel, QC; Andre Kokis, Centre Hospitalier de
l’Université de Montréal (CHUM) St-Luc Hospital, Montreal, QC; Paolo Costi, Centre
Hospitalier de l’Université de Montréal (CHUM) Hôtel-Dieu, Montreal, QC; Ian Paterson,
Mazankowski Alberta Heart Institute, Edmonton, AB; Alan Lipson, Victoria General
Hospital, Winnipeg, MB; John Jue, Vancouver Coastal Health, Vancouver, BC; Jean-Pierre
Déry, Quebec Heart and Lung Institute, Quebec City, QC; Laurence Descarries, Cité de la
Santé, Laval, QC; Colin Pearce, Saskatchewan Drug Research Institute, Saskatoon, SK;
Serge Lepage, Centre Hospitalier de l’Université de Sherbrooke, Sherbrooke, QC; India:
Dorairaj Prabhakaran (country coordinator), Centre for Chronic Disease Control (CCDC),
New Delhi; Rakesh Yadav and Ambuj Roy, All India Institutes of Medical Sciences, New
Delhi; Iran: Nizal Sarrafzadegan, Isfahan Cardiovascular Research Institute, Isfahan;
Pakistan: Nasreen Adamjee, Interactive Research & Development, Karachi; Tunisia: Habib
Gamra, University Hospital F. Bourguiba, Monastir; United States: Kochunni Mohan, Bay
Regional Medical Center, Bay City, MI; Pedro Lozano, DVA Medical Center, Oklahoma
City, OK; Luis Gruberg, Stony Brook University Medical Center, Stony Brook, NY; Allan
Murphy, Riverside Regional Medical Center, Newport News, VA; Harvey Hahn, Kettering
Medical Center, Kettering, OH; Milton Nathan, Kettering Medical Center, Kettering, OH;
Dhananjai Menzies, Bassett Healthcare, Copperstown, NY; Richard Terry, United Health
Services, Johnson City, NY; George Gibson, Parkview Medical Center, Pueblo, CO;
Mitchell Rashid, Charleston Area Medical Center, Charleston, PA; Marian Taylor, Medical
University of South Carolina, Charleston, SC; Robert Weiss, Central Maine Medical Center,
Lewiston, ME.
Steering Committee
Mark J. Eisenberg, Jewish General Hospital, Montreal, QC, Canada; André Gervais, Agence
de la santé et des services sociaux, Direction de santé publique, Montréal, QC, Canada;
Lawrence Joseph, McGill University, Montreal, QC, Canada; Jennifer O’Loughlin,
Université de Montréal, Montréal, QC, Canada; Gilles Paradis, McGill University, Montreal,
QC, Canada; Louise Pilote, Montreal General Hospital, Montreal, QC, Canada; Stéphane
Rinfret, Quebec Heart-Lung Institute, Quebec, QC, Canada.
Data Safety Monitoring Board
Stanley Nattel (Chair), Montreal Heart Institute, Montreal, QC, Canada; Koon K. Teo,
McMaster University, Hamilton, ON, Canada; James D. Neaton, University of Minnesota,
Minneapolis, MN, USA.
Endpoints Evaluation Committee
Vidal Essebag, McGill University Health Centre and Hôpital Sacré-Coeur de Montréal,
Montréal, QC, Canada; Igal A. Sebag, Jewish General Hospital, Montreal, QC, Canada.
Online Table 2. Inclusion and Exclusion Criteria.
Inclusion Criteria
1. Age ≥ 18 years.
2. Smokes ≥ 10 cigarettes per day, on average, for the past year.
3. Suffered an ACS and planned hospitalization of ≥ 24 hours. ACS is defined as positive
Troponin T, Troponin I, or CK-MB levels and ≥ 1 of the following:
1. Ischemic symptoms (i.e. typical chest pain) for at least 20 minutes.
2. ECG changes indicative of ischemia (ST-segment elevation or depression).
3. Development of pathological Q waves on the ECG.
Note: If patient is to undergo percutaneous coronary intervention (PCI) and/or coronary
artery bypass graft surgery (CABG), they are still eligible to be enrolled.
4. Willing to consider smoking cessation.
5. Able to read and understand English or French.
6. Likely to be available for follow-up.
Exclusion Criteria
1. Current seizure disorder, history of seizures, or predisposition to seizures (e.g. history of
brain tumor, severe head trauma, or stroke).
2. Current use of medications that lower seizure threshold, e.g. amantadine, anti-depressants,
anti-malarials, anti-psychotics, levodopa, lithium, quinalone antibiotics, ritonavir, systemic
steroids, theophyllin, type 1C antiarrhythmics (e.g. encainide, flecainide, propafenone).
3. Current use of Wellbutrin or any other medications that contain bupropion.
4. Current use of any medical therapy for smoking cessation (e.g. BuSpar, doxepin,
fluoxetine, nicotine gum, or nicotine patch).
5. Excessive alcohol consumption defined as ≥ 14 alcoholic drinks per week.
6. Use of MAO inhibitors or thioridazine in the past 15 days.
7. Current diagnosis of major depression (requiring medication), bipolar disease, or dementia.
8. History of suicidal events (previous suicide attempt, suicidal ideation) or family history of
suicide.
9. History of anorexia nervosa or bulimia.
10. Current use of over-the-counter stimulants (e.g. ephedrine, phenylephrine) or anorectics.
11. Diagnosed hepatic failure, cirrhosis, hepatitis or history of hepatic impairment (AST or
ALT levels ≥ 2 times upper limit of normal prior to admission for ACS).
12. Renal impairment (creatinine levels ≥ 2 times upper limit of normal).
13. Pregnancy or lactation.
14. Use of any illegal drugs in the past year (e.g. opiates, cocaine, heroin).
15. Likely to be unavailable for follow-up.
16. Medical condition with a prognosis of less than 1 year.
Online Table 3. Baseline Counseling Script
1. Ask, Assess: smoking and quitting:
 “How many cigarettes per day do you smoke and for how long have you smoked?”
 “Have you tried to quit, how long did it last and what made you start again?”
 “Are you thinking about quitting smoking following what happened?”
2. Advise: clear and positive
 “You’re putting yourself at great risk by smoking, but stopping can greatly increase
your chance of living longer and better.”
 “Your risk of dying suddenly decreases within hours of stopping smoking. Your risk of
having another heart attack will decrease by 50% within a year, and you will also
decrease the risk of many other diseases like stroke, blocked peripheral blood vessels,
lung cancer and other cancers, chronic bronchitis and emphysema, impotence, etc.
 “There are many more advantages of quitting: you will have more energy, it will be
easier to breathe, you will have more money, people around you will be healthier, etc.”
 “I am very concerned about you and I feel that quitting smoking is the most important
decision you can make right now!”
3. Ask: likes and dislikes about smoking, reasons for quitting and worries about quitting
 “What do you like about smoking?”
 “Are there things you do not like about smoking?”
 “What is your main worry about trying to quit smoking?”
 “What is your main reason for quitting smoking?”
4. Advise: withdrawal, weight gain and strategies
 Discuss the worries:
o Withdrawal symptoms: irritability, anxiety, difficulty concentrating, sleep
disturbances, headache, uncontrollable desire to smoke, constipation, increased
sweating, dizziness, increased appetite and weight gain.
o Discuss ways to manage stress (avoiding stressful situations, exercise, etc.)
 Explain that the study medication will decrease withdrawal and reduce weight gain and
that the maximum effect should be felt as of the 8th day of treatment.
 Identify factors triggering the urge to smoke (drinking coffee or alcohol, driving, being
with other smokers) and help patients design strategies to handle them.
o Review instructions on how to use bupropion (see Patient Information Sheet).
5. Assist, Arrange: material and support
 Congratulate and encourage the patient by telling them you are sure that they can quit
smoking.
 Encourage them to identify people willing to provide support in their environment.
 Offer educational material.
Remind them that you are available if they have problems and inform them of what to do
and where to go in case of an emergency.
Online Table 4. Follow-up Counseling Script I
1. Ask, Assess:
 “Have you smoked any cigarettes (even a puff) since the last time? [Congratulate if has not smoked.
Encourage not to smoke if has smoked.]
 “How are you feeling?” (more energy, easier to breathe, have more money, people around are happy,
etc.)
2. Advise: clear and positive
 “Having stopped smoking greatly increases your chance of living longer and better.”
 “Your risk of dying has already decreased. Your risk of having another heart attack will decrease by
50% within a year. You will also decrease the risk of many other diseases like stroke, blocked
peripheral blood vessels, lung cancer and other cancers, chronic bronchitis and emphysema, impotence,
etc.”
 “Quitting is the most important change you could make!”
3. Ask: withdrawal, difficulties and worries about quitting
 Ask about difficulties (what and when)o Withdrawal symptoms: irritability, anxiety, difficulty concentrating, sleep disturbances,
headache, dizziness, uncontrollable desire to smoke, constipation, increased sweating, increased
appetite and weight gain.
o Tricks they are using to deal with cravings, stress, etc.
 “What is your main difficulty right now?”
4. Advise: strategies
 Explain that the study medication bupropion will decrease withdrawal symptoms and weight gain.
 Identify factors triggering their urge to smoke (getting up in the morning, drinking coffee or alcohol,
driving, being with other smokers) and help them design strategies to handle them.
 Remind them how to use bupropion.
o Dosage: 150 mg twice a day, never take more than two pills per day and never less than eight
hours apart, never split or crush the pills. (Note: the dosage for the first three days of treatment
is 150 mg per day).
o Remind them of the most frequent side effects (insomnia, dry mouth) and rare but possible side
effects (seizures, tremors, rashes, feeling very high or depressed).
o Remind patients not to abruptly discontinue their alcohol or sedative use (Ativan, Valium,
Imovan, Serax, Dalmane, etc.).
5. Assist, Arrange: support
 Congratulate and encourage the patient by telling them you are sure they will continue not to smoke.
 Encourage them to identify people willing to provide support in their environment.
 Remind them that you are available if they have problems and inform them of what to do and where to
go in case of an emergency.
Online Table 5. Definitions of Clinical Events.
Unstable Angina
a. New cardiac symptoms and positive ECG findings with normal biomarkers.
b. Changing symptom pattern and positive ECG findings with normal biomarkers.
Acute Coronary Syndrome (ACS)
Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent ACS:
a. Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of
biochemical markers of myocardial necrosis with at least one of the following:
i.
ischemic symptoms
ii.
development of pathologic Q waves on the ECG
iii.
ECG changes indicative of ischemia (ST-segment elevation or depression)
iv.
coronary artery intervention (e.g. coronary angioplasty)
b. Pathologic findings of an acute ACS
Death
a. Definite or probable fatal ACS
b. Possible fatal coronary event
c. Definite fatal CHD
d. Non-CHD death
e. Unclassifiable
Seizure
Seizures will be characterized by sudden disturbance of conciousness, motor function, sensory
function, or autonomic function. These behavioral events must be accompanied by at least one
of the following:
a. interictal or ictal epileptiform EEG abnormalities
b. post-ictal state (e.g. retrograde amnesia, confusion, somolence, etc.)
c. tongue-biting
d. sphincteric incontinence