Background and Importance:~Patients who continue to smoke after an acute coronary syndrome (ACS), including myocardial infarction and unstable angina, have a 35% increased risk of reinfarction or death compared with those who quit. Previous smoking cessation trials conducted by the investigators have established varenicline (Champix) as the gold standard for patients with ACS. However, more than 50% of patients motivated to quit who receive varenicline for 12 weeks immediately post-ACS will return to smoking within 6 months. Therefore, more effective smoking cessation strategies are needed. Based on newly available data from randomized controlled trials (RCTs), including the investigators' E3 Trial, which suggest that nicotine e-cigarettes are more efficacious for smoking cessation than other nicotine replacement therapies and counselling alone, the investigators propose to combine varenicline and nicotine e-cigarettes. The proposed combination therapy is a novel approach needed now to increase abstinence in patients with ACS.~Goal(s)/Research Aims:~The Aggressive Smoking Cessation Therapy Post-Acute Coronary Syndrome (ASAP) Trial is a 5-year, multi-centre RCT that will assess the efficacy, safety, and tolerability of aggressive smoking cessation therapy initiated in-hospital following ACS. The specific aims are:~To assess the efficacy of combination therapy (varenicline and nicotine e-cigarettes) versus varenicline alone for 12 weeks, in terms of biochemically-validated 7-day point prevalence and continuous smoking abstinence, and ≥50% reduction in daily cigarette consumption at 24 and 52 weeks post-ACS.~To describe the safety and tolerability of varenicline combined with nicotine e-cigarettes, in terms of serious adverse events (SAEs), adverse events (AEs), treatment discontinuation due to side effects, and therapy adherence over the 12-week treatment period.~Methods/Approaches/Expertise:~A total of 798 participants will be randomized 1:1 to: (1) varenicline and nicotine e-cigarettes, or (2) varenicline alone for 12 weeks, with follow-up of 52 weeks. Both arms will receive individual smoking cessation counselling. Participants randomized to combination therapy (varenicline and nicotine e-cigarette) will be given funds to cover the purchase of e-cigarettes and nicotine cartridges. Funds will be provided at discharge for the first 4 weeks of e-cigarette use. Participants who follow the e-cigarette purchasing instructions and provide receipts at subsequent clinic visits will be provided additional funds at week 4 (for weeks 4 to 8) and reimbursed at week 12 (for weeks 8 to 12). Participants will begin varenicline (titrated to 1.0 mg twice daily) and counselling in-hospital, and e-cigarette use (if applicable) upon discharge. Eligible patients will be hospitalized for ACS, self-identify as regular smokers (≥10 cigarettes/day for ≥1 year), and be motivated to quit. Participants will complete telephone follow-ups at weeks 1, 2, 8, and 18, and clinic visits at weeks 4, 12, 24, and 52. The investigators will collect information about self-reported smoking, treatment adherence, and adverse events. Self-reported smoking abstinence will be biochemically-validated at clinic visits using exhaled carbon monoxide (≤10 ppm). The primary endpoint will be biochemically-validated 7-day point prevalence smoking abstinence at 24 weeks. With 399 participants per arm and an alpha of .05, the investigators will have 80% power to detect a ≥ 10% difference in abstinence at 24 weeks. The ASAP trial will be conducted by a highly experienced team of researchers and enrolling centres, who have previously completed three smoking cessation RCTs, including two in patients with ACS.~Expected Outcomes:~Smoking cessation post-ACS is essential to reduce morbidity and mortality in this high-risk patient population. ASAP will provide regulators, health care professionals, and smokers with important information about the efficacy of combination varenicline and nicotine e-cigarettes for smoking cessation in patients with ACS.
The ASAP Trial is a 5-year, multi-centre, randomized controlled trial that will assess the efficacy, safety, and tolerability of aggressive smoking cessation therapy initiated in-hospital following ACS. It will recruit 798 adult patients smoking on average at least 10 conventional (tobacco) cigarettes per day who are motivated to quit smoking and have been diagnosed with ACS requiring hospitalization. Patients will be randomized (1:1) to one of two treatment arms: (1) combination therapy of varenicline and nicotine e-cigarettes plus counseling or (2) varenicline plus counseling for 12 weeks, with 52-week follow-up.