Aggressive Smoking Cessation Trial (ASAP)

Inclusion Criteria: 1. Patients currently hospitalized or being discharged from hospital who have suffered an ACS, defined as follows: i. MI, defined by positive troponin T, troponin I, or CK-MB levels (as defined by institution-specific cut-offs) and ≥ 1 of the following: 1. Ischemic symptoms for ≥ 20 min; 2. Electrocardiogram (ECG) changes indicative of ischemia (ST-segment elevation or depression); 3. Development of pathological Q waves on the ECG ii. Unstable angina with significant coronary artery disease, defined by all of the following: 1. Ischemic symptoms for ≥ 20 min; 2. ECG changes indicative of ischemia (ST-segment changes); 3. At least one lesion ≥ 50% on angiogram performed during the current hospitalization. \[Note: patients who undergo cardiac catheterization or percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery will be eligible provided they are able to start varenicline in-hospital and nicotine e-cigarette at discharge.\] OR Outpatients with the following diagnoses/conditions: i. Cardiovascular: 1. Coronary artery disease documented with angiography or coronary CT; 2. Previous ACS, MI, stable or UA; 3. Previous coronary revascularization (e.g. PCI or CABG). ii. Renovascular: a. Chronic kidney disease. iii. Cerebrovascular: a. Previous cerebral infarction or transient cerebral ischemic attack. iv. Peripheral vascular: 1. Abdominal aortic aneurysm \> 3.0 cm or previous aortic aneurysm surgery; 2. Ankle-brachial pressure index of \< 0.9 or intermittent claudication; 3. Documented carotid artery disease; 4. Lower-limb amputation; 5. Previous lower-limb bypass surgery or angioplasty. v. ≥1 risk factors: 1. BMI ≥ 27 kg/m2; 2. Dyslipidemia; 3. Family history (first degree relative: parents or siblings only) of coronary heart disease or stroke before the age of 60 years; 4. Hypertension; 5. Males aged ≥ 55 years/females aged ≥ 60 years; 6. Diabetes mellitus. vi. Heart-related conditions: <!-- --> 1. Atrial fibrillation or flutter; 2. Cardiomyopathy; 3. Heart failure; 4. Left ventricular hypertrophy (evidenced by echocardiography or ECG); 5. Valvular disease (evidenced by echocardiography). 2. Smoked on average ≥ conventional cigarettes/day for the past year; 3. Age ≥18 years; 4. Motivated to quit smoking according to the Motivation To Stop Scale (MTSS) (≥ level 5); 5. Able to understand and provide informed consent in English or French; 6. If randomized to the combination arm (varenicline and e-cigarette plus counseling), willing and able to purchase e-cigarettes with the following properties: rechargeable, closed system that uses sealed cartridges or pods, tobacco or no flavor only, and nicotine strength of 20 mg/ml (2%) or less; 7. Likely to be available for 52 weeks of follow-up. Exclusion Criteria: 1. Pregnant or lactating females; 2. Use of any of the following in the 30 days prior to eligibility assessment: i. Varenicline or bupropion for smoking cessation; ii. Nicotine or non-nicotine e-cigarettes; iii. Other anti-craving medication (e.g., naltrexone, acamprosate) with the potential to alter substance-seeking behaviors; 3. Use of nicotine replacement therapy (NRT) in the 7 days prior to eligibility assessment \[Note: If participant is prescribed non-study NRT while hospitalized, they can continue using the non-study NRT until being discharged, even while taking the investigational products. Upon discharge, use of the non-study NRT should be stopped.\]; 4. Use of varenicline or e-cigarettes (nicotine or non-nicotine) for ≥14 days consecutively in the past year; 5. Previous serious adverse reaction to varenicline and/or e-cigarettes (nicotine or non-nicotine); 6. NYHA or Killip Class III or IV at the time of randomization; 7. Any unstable psychiatric disorder (as per enrolling physician); 8. Renal impairment with creatinine levels ≥2 times upper limit of normal or eGFR ≤15; 9. Use of any illegal drugs in the past year; 10. Planned use of cannabis (smoked) or other tobacco products (smoked or other) during the study period. \[Note: use of cannabis which is not smoked is permitted (e.g., edibles, ingested or vaped oils). However, methods which involve combustion could invalidate biochemical validation via exhaled carbon monoxide.\]