• 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:

⁃ Ischemic symptoms for ≥ 20 min;

⁃ Electrocardiogram (ECG) changes indicative of ischemia (ST-segment elevation or depression);

⁃ Development of pathological Q waves on the ECG

• ii. Unstable angina with significant coronary artery disease, defined by all of the following:

⁃ Ischemic symptoms for ≥ 20 min;

⁃ ECG changes indicative of ischemia (ST-segment changes);

⁃ 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:

⁃ Coronary artery disease documented with angiography or coronary CT;

⁃ Previous ACS, MI, stable or UA;

⁃ 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:

⁃ Abdominal aortic aneurysm \> 3.0 cm or previous aortic aneurysm surgery;

⁃ Ankle-brachial pressure index of \< 0.9 or intermittent claudication;

⁃ Documented carotid artery disease;

⁃ Lower-limb amputation;

⁃ Previous lower-limb bypass surgery or angioplasty.

• v. ≥1 risk factors:

⁃ BMI ≥ 27 kg/m2;

⁃ Dyslipidemia;

⁃ Family history (first degree relative: parents or siblings only) of coronary heart disease or stroke before the age of 60 years;

⁃ Hypertension;

⁃ Males aged ≥ 55 years/females aged ≥ 60 years;

⁃ Diabetes mellitus. vi. Heart-related conditions:

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‣ Atrial fibrillation or flutter;

⁃ Cardiomyopathy;

⁃ Heart failure;

⁃ Left ventricular hypertrophy (evidenced by echocardiography or ECG);

⁃ Valvular disease (evidenced by echocardiography).

• Smoked on average ≥ conventional cigarettes/day for the past year;

• Age ≥18 years;

• Motivated to quit smoking according to the Motivation To Stop Scale (MTSS) (≥ level 5);

• Able to understand and provide informed consent in English or French;

• 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;

• Likely to be available for 52 weeks of follow-up.