Journal of the American Society of Hypertension
Review ArticleCardiovascular effects of pharmacologic therapies for smoking cessation
Introduction
Tobacco dependence is a potent risk factor for cardiovascular (CV) diseases, including coronary heart disease, peripheral vascular disease (PVD), stroke, and aortic abdominal aneurysm.1 Despite known harms of smoking and benefits associated with quitting, approximately 20% of the adult population with CV diseases or hypertension (HTN) continue to smoke.2
National practice guidelines recommend seven pharmacotherapies to aid in quitting, including five nicotine replacement (NRT) therapies, bupropion sustained-release (SR), and varenicline (Table 1).3 Extensive research has demonstrated these therapies to be superior to placebo for short- and intermediate-term smoking cessation.3 More recently, trials have been conducted in patients with CV disease, to evaluate the benefit–risk profiles.4, 5, 6 Because of their mechanisms of action, some smoking cessation therapies may have the potential to increase CV risk, particularly if patients who still smoke. This review analyzes CV effects of smoking cessation therapies, particularly in patients with CV disease.
Section snippets
Mechanisms for Cardiovascular Adverse Effects
NRT represents a cornerstone of managing tobacco dependence, although quit rates on NRT are disappointing (19–27%).3 Shortly after approval by the Food and Drug Administration (FDA) in the mid-1980s, reports of atrial fibrillation, myocardial infarction, and stroke associated with NRT use began to surface.7, 8, 9 Subsequently, substantive research was undertaken to characterize the impact of nicotine and NRT on the CV system. Smoking increases CV event risk and through nicotine, increases
Bupropion SR
Bupropion SR (Zyban) was approved for tobacco dependence in 1997 as the first non-nicotine option, although previously available for the treatment of depression. Although the mechanism for smoking cessation remains unclear, the drug inhibits the reuptake of norepinephrine and dopamine.33 Nicotine stimulates the mesolimbic system and the dopamine reward pathway to promote and reinforce the behaviors of smoking; it is thought that bupropion may interfere with this pathway.34 Although the main
Varenicline
Varenicline, approved in 2006, is a partial and highly selective agonist of the alpha-4-beta-2 nicotinic acetylcholine receptors, which attenuates nicotine withdrawal symptoms while inhibiting the surge of dopamine release. This dopamine surge is believed to reinforce the behavior of smoking.42, 43 Varenicline is also a potent and full agonist at the alpha-7 subunit and a partial agonist at the alpha-3-beta-4 subunit of nicotine acetylcholine receptors.44 Activity at these subunits may
Clinical Perspectives
The benefits of quitting smoking are substantial, and despite this, patients with CV conditions continue to smoke. Effective therapies to aid in smoking cessation are available, and are recommended by practice guidelines.3 The concern of adverse CV effects from these therapies is appropriate, particularly in patients with existing CV disease. Fortunately drug-related risks are likely short-term, whereas the patient is taking therapy. However, the benefits derived from a successful quit attempt
References (52)
- et al.
Cardiovascular toxicity of nicotine: implications for nicotine replacement therapy
J Am Coll Cardiol
(1997) Cigarette smoking and cardiovascular disease: pathophysiology and implications for treatment
Prog Cardiovasc Dis
(2003)- et al.
Safety issues in pharmacotherapy for smoking in patients with cardiovascular disease
Prog Cardiovasc Dis
(2003) - et al.
The pathophysiology of cigarette smoking and cardiovascular disease. An update
J Am Coll Cardiol
(2004) - et al.
Nicotine patch therapy in smoking cessation reduces the extent of exercise-induced myocardial ischemia
J Am Coll Cardiol
(1997) - et al.
Cardiovascular effects of transdermal nicotine in mildly hypertensive smokers
Am J Hypertens
(2001) - et al.
Endothelin ET(A) receptor antagonism attenuates the pressor effects of nicotine in rats
Eur J Pharmacol
(2000) - et al.
Risk of acute first myocardial infarction and use of nicotine patches in the general population
J Am Coll Cardiol
(2001) - et al.
Safety and effectiveness of transdermal nicotine patch in smokers admitted with acute coronary syndromes
Am J Cardiol
(2005) - et al.
Safety profile of sustained-release bupropion in depression: results of three clinical trials
Clin Ther
(1999)
Bupropion for smokers hospitalized with acute cardiovascular disease
Am J Med
Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid
Neuropharmacology
The effect of varenicline on heart rate variability in healthy smokers and nonsmokers
Autonom Neurosci Basic Clin
Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline
Nicotine replacement therapy for patients with coronary artery disease
Arch Intern Med
The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease
N Engl J Med
Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial
Circulation
Atrial fibrillation while chewing nicotine gum
JAMA
Eur Heart J
Stroke following application of a nicotine patch
Ann Pharmacother
Pharmacologic aspects of cigarette smoking and nicotine addiction
N Engl J Med
Acute effects of low dose nicotine gum on platelet function in non-smoking hypertensive and normotensive men
Eur J Clin Pharmacol
Effects of transdermal nicotine patches on ambulatory ECK monitoring findings: A double-blind study in healthy smokers
Cardiovasc Drugs Ther
The influence of smoking and of oral and transdermal nicotine on blood pressure, and haematology and coagulation indices
Thromb Haemost
Cited by (19)
Frequently Reported Adverse Events With Smoking Cessation Medications: Post Hoc Analysis of a Randomized Trial
2021, Mayo Clinic ProceedingsDesign and Evaluation of Systemic Administration of Nano Silica MCM48:Eu3+ in Mouse Brain
2023, Journal of the Brazilian Chemical SocietyAgents for Treatment of Withdrawal and Dependency: Varenicline
2022, NeuroPsychopharmacotherapyPharmacovigilance assessment of cardiac implications of nicotine replacement therapy among smokers
2020, Current Drug SafetySpecial topics in smoking cessation: Patients with cardiovascular disease and updates on e-cigarettes
2019, Connecticut Medicine
This research and preparation of this report was supported by National Institutes of Health grants R01DA024667 and R01 R01AG022092.