Speakers - 2026

Title: Comparing Post-Cessation Cardiovascular Outcomes and Weight Gain with Varenicline Versus Nicotine Replacement Therapy

Abstract

Background: Smoking cessation is an important step in reducing cardiovascular complications and mortality associated with tobacco use. Widely used pharmacological therapies such as Chantix and nicotine replacement therapies (NRT) are accepted as first- and second-line treatments to aid in the process of cessation. However, the incidence of major adverse cardiovascular events (MACE) associated with the use of these therapies is rarely assessed. Secondarily, the effects of different cessation modalities on weight gain and its subsequent cardiometabolic consequences are also sparsely studied. A better understanding of the association between varenicline and cardiovascular risk, as well as post-cessation weight gain, compared with NRT and other cessation methods, may help guide clinical decision-making toward the selection of pharmacological therapies for smokers who wish to reduce morbidity.

Objective: To assess the significance of MACE and weight gain in post-cessation populations that use varenicline compared to those that use nicotine replacement therapy.

Methods: This study is a systematic review evaluating studies identified through PubMed, Embase, and the Cochrane Library published from 2005–2025. Studies were eligible if they included randomized controlled trials and cohort studies that evaluated adults undergoing smoking cessation with varenicline, NRT, or other pharmacologic therapies. Outcomes included incidence values of post-cessation weight gain and MACE (including MI, stroke, cardiovascular death, and hospitalization for heart failure or unstable angina).

Results: After selection, a total of 10 studies were included: 3 randomized controlled trials (RCTs) and 7 observational studies. Overall, there was no significant increase in MACE associated with varenicline or nicotine replacement therapy. Nine of ten studies showed equivalent or non-significant rates of cardiovascular risk between these two therapies compared to placebo or other methods. Of these 9, an RCT analyzing patients with acute coronary syndrome showed that MACE was 4.0% with varenicline vs. 4.6% with placebo. Another RCT evaluating patients with stable cardiovascular disease found that MACE was numerically higher with varenicline (7.1% vs. 5.7% with placebo), although the difference was not statistically significant. An observational study distinct from the other nine suggested a potential shortterm increase in cardiovascular risk, reporting a relative incidence of cardiovascular events of 1.34 during the 12 weeks following varenicline initiation. However, the absence of a comparator group limits the strength of this finding. Post-cessation weight gain was observed across all cessation therapies but was found to be highly dependent on individual cardiometabolic factors, as well as the severity of underlying disease, if present. This review acknowledges the limitations related to study heterogeneity and the predominance of observational data. 3

Conclusions: Current evidence supports the overall cardiovascular safety of varenicline and NRT for smoking cessation. These medications do not demonstrate a significant increase in MACE. Post-cessation weight gain appears to reflect the metabolic effects of smoking cessation and individual patient factors more than medicationrelated effects. Future studies should adopt more standardized approaches to evaluating cardiovascular and weight-related outcomes to better define cardiometabolic outcomes associated with smoking cessation pharmacotherapies.