Cardiovascular Adverse Events Associated with Smoking-Cessation Pharmacotherapies

Abstract

Smoking continues to be the leading cause of preventable deaths in the USA, accounting for one in every five deaths every year, and cardiovascular (CV) disease remains the leading cause of those deaths. Hence, there is increasing awareness to quit smoking among the public and counseling plays an important role in smoking cessation. There are different pharmacological methods to help quit smoking that includes nicotine replacement products available over the counter, including patch, gum, and lozenges, to prescription medications, such as bupropion and varenicline. There have been reports of both nonserious and serious adverse CV events associated with the use of these different pharmacological methods, especially varenicline, which has been gaining media attention recently. Therefore, we systematically reviewed the various pharmacotherapies used in smoking cessation and analyzed the evidence behind these CV events reported with these therapeutic agents.

Assessment of a Potential Pharmacokinetic Interaction between Nebivolol and Bupropion in Healthy Volunteers

“…A potential interfering factor with the PD outcome of this study is related to bupropion, an antidepressant that, at higher doses, can increase HR and BP due to sympathomimetic activity [37,38] . However, the incidence of hypertension was at its highest (6.1%) when associated with a nicotine transdermal patch [39] and that was not the case in this study.…”

Cardiovascular adverse events in the drug‐development program of bupropion for smoking cessation: A systematic retrospective adjudication effort

“…The safety of bupropion for smoking cessation was also reported in a recently published meta‐analysis, which suggests a protective effect with bupropion (risk ratio: 0.45, 95% CI: 0.21‐0.85) with regard to CV events . Conversely, a post‐marketing analysis in France found that in the 3 years after bupropion was approved for smoking cessation, 698 000 patients were prescribed the drug, and rates of CV events reported to the French Regional Pharmacovigilance Centres or GSK included ischemic heart disease in 10.1% and sudden death in 2.3% within 2 weeks of drug initiation .…”

“…The safety of bupropion for smoking cessation was also reported in a recently published meta-analysis, which suggests a protective effect with bupropion (risk ratio: 0.45, 95% CI: 0.21-0.85) with regard to CV events. 4,5 Conversely, a post-marketing analysis in France found that in the 3 years after bupropion was approved for smoking cessation, 698 000 patients were prescribed the drug, and rates of CV events reported to the French Regional Pharmacovigilance Centres or GSK included ischemic heart disease in 10.1% and sudden death in 2.3% within 2 weeks of drug initiation. 6 These event rates are significantly higher than in our study; however, AEs in the French post-marketing analysis were based on physician reporting and were not adjudicated, and there was no control in a population of smokers at high risk for coronary artery disease.…”

Smoking Cessation, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology

“…Importantly, systematic reviews and meta-analyses of RCT data have not identified a significant link between varenicline and increased risk of serious cardiovascular adverse events. 66,[83][84][85] However, the cardiovascular safety of varenicline has remained a topic of interest and concern, [86][87][88] although the cardiovascular risks of continued smoking has been extensively documented. 89 In a 2015 retrospective review of 164,766 individuals who received pharmacotherapy for smoking cessation (varenicline, n551,450; NRT, n5106,759; bupropion, n56,557), neither varenicline nor bupropion posed an elevated risk of cardiovascular or neuropsychiatric (ie, depression, self-harm) events compared with NRT.…”