Review Article
Cardiovascular effects of pharmacologic therapies for smoking cessation

https://doi.org/10.1016/j.jash.2012.11.003Get rights and content

Abstract

Tobacco dependence is a potent risk factor for cardiovascular (CV) diseases and, despite known harms of smoking and benefits associated with smoking cessation, approximately 20% of the adult population with CV diseases or hypertension continue to smoke. Extensive research has demonstrated that nicotine replacement, varenicline, and bupropion sustained-release are superior to placebo for short- and intermediate-term smoking cessation. Because of their mechanisms of action, some smoking cessation therapies have been thought to have the potential to increase CV risk, particularly if the pharmacotherapies are taken while individuals are still smoking. Hence, we have analytically reviewed the literature describing the CV effects of therapies for smoking cessation, particularly as they apply to patients with CV disease.

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

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    This research and preparation of this report was supported by National Institutes of Health grants R01DA024667 and R01 R01AG022092.

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