Aggressive Smoking Cessation Trial (ASAP)

Prior treatment

• Use of any of the following in the 30 days prior to eligibility assessment:
  • 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;
• Use of nicotine replacement therapy (NRT) in the 7 days prior to eligibility assessment \[Note: If participant is prescribed non-study NRT while hospitalized, they can continue using the non-study NRT until being discharged, even while taking the investigational products. Upon discharge, use of the non-study NRT should be stopped.\];
• Previous serious adverse reaction to varenicline and/or e-cigarettes (nicotine or non-nicotine);
• Use of any illegal drugs in the past year;

Other illness

• Any unstable psychiatric disorder (as per enrolling physician);

Lab values

• Renal impairment with creatinine levels ≥2 times upper limit of normal or eGFR ≤15;

Other

• Pregnant or lactating females;
• Use of varenicline or e-cigarettes (nicotine or non-nicotine) for ≥14 days consecutively in the past year;
• NYHA or Killip Class III or IV at the time of randomization;
• Planned use of cannabis (smoked) or other tobacco products (smoked or other) during the study period. \[Note: use of cannabis which is not smoked is permitted (e.g., edibles, ingested or vaped oils). However, methods which involve combustion could invalidate biochemical validation via exhaled carbon monoxide.\]

• Patients currently hospitalized or being discharged from hospital who have suffered an ACS, defined as follows:
  • 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
  • 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:
  • 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:
  • Chronic kidney disease. iii. Cerebrovascular:
  • 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.
  • ≥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.