Background

Epidemiology

• Worldwide, >1 billion individuals use tobacco products.
• In the US, 15.5% of adults currently smoke cigarettes, 76% of those daily and 24% less than daily.
  • Smoking prevalence is disproportionally higher among those with less education, lower incomes, and co-occurring psychiatric and substance use disorders.
• Tobacco causes over 6 million annual deaths globally per year with >480,000 in the US yearly.
• Leading cause of preventable death worldwide.
• Life expectancy for those who smoke is 10 years shorter than a nonsmoker.

Neurobiology

• Nicotine binds to acetylcholine receptors, resulting in release of dopamine, norepinephrine, serotonin, GABA, endorphins, and other neurotransmitters.
• Nicotine causes release of dopamine in the limbic center of the brain, leading to positive reinforcement pathways associated with continued use.

Smoking and CV disease

• Individuals who continue smoking after CV event or revascularization procedure have worse outcomes, compared with those who stop.
  • After MI, smoking continuation had higher risk of recurrent coronary event, stroke, TIA, or death.
  • After CAD intervention, smoking continuation had greater risk of all-cause mortality, cardiac death, and need for another procedure.

Smokeless tobacco

• Smokeless tobacco was associated with increased risk for fatal MI and stroke.
• Following MI, those who continue smokeless tobacco have a substantially higher 2-year mortality compared with those who quit.

Benefits from treating tobacco use disorder:

• Treatment of tobacco use disorder reduces risk of overall mortality among adults who smoke, even if cessation occurs after age 65 or after development of tobacco related disease.
  • Greatest mortality benefit is seen in those who stop smoking before age 40.
• Risk of tobacco related disease declines to nonsmoker level in 15 years for CAD and in 5-15 years for stroke.
• For people who smoke and have an MI, stopping smoking reduces subsequent mortality by 15-61%, increases quality of life, and reduces angina.
• For people who smoke with COPD, stopping smoking slows rate of lung function decline, reduces symptoms and likelihood of exacerbations, and lowers all-cause mortality.
• For people who smoke with lung cancer, stopping smoking reduces risk of recurrence, development of second primary cancer and mortality.
• Reduction without stopping cigarette consumption is not associated with a decrease in overall mortality or tobacco associated mortality.

Nicotine Dependence

• Combination of physical dependence and ingrained learned behavior.
  • Physical dependence: nicotine binds to nicotinic acetylcholine receptors in the brain, leading to release of neurotransmitters with rewarding effect; repeated use leads to upregulation of nicotine receptors, tolerance, dependence and withdrawal.
• Nicotine withdrawal:
  • Symptoms: cravings, irritability, anxiety, restlessness, dysphoria, impaired concentration, hunger.
  • Symptom duration: 2 weeks to 6 months.

Treatment

• Counseling
  • The “5A” model: Ask about use, advise users to quit, assess readiness to quit, assist in quit attempts, arrange follow up.
  • Behavioral strategies include motivational interviewing and education focused on self-monitoring smoking behavior, managing triggers, setting a quit date (if their goal), and identifying social support.
  • Telephone hotlines can provide counseling sessions.
  • Addressing tobacco use in patients with other substance use disorders does not negatively impact treatment of other substance use disorders.
• Medications
  • Nicotine replacement therapy (NRT):
    • NRT increases smoking abstinence by 60% compared to placebo.
    • Associated with an increase in CV events, but not major CV events, when compared with placebo.
      • However, study that focused on outpatient people who smoke with CVD found no significant increase in CV events among people who smoke using nicotine patch v. placebo.
  • Bupropion:
    • Monocyclic antidepressant.
    • Increases smoking cessation rates compared to placebo.
    • Not associated with increase in major adverse cardiovascular events.
  • Varenicline:
    • Nicotinic acetylcholine receptor antagonist.
    • Doubles rates of abstinence compared with placebo.
    • Meta-analyses have shown superiority to bupropion for cessation.
    • No increase in CV events compared with NRT, bupropion or placebo.
    • Concern for increased risk of depression with varenicline, and former FDA black box warning for suicidality removed. Studies have not shown increased neuropsychiatric events on varenicline.
  • Nortriptyline:
    • 2^nd line.
    • Meta-analysis demonstrates benefit over placebo but non-significant benefit over bupropion; no benefit as adjunct medication to NRT.

E-cigarettes (“vaping”):

• Usefulness and recommendation for use are controversial.
• Clinical efficacy for smoking cessation is debated, but can consider it harm reduction.
• Cochrane meta-analysis:
  • Concluded that e-cigarette users were more likely to abstain from cigarette smoking for at least 6 months compared with placebo e-cigarette users.
  • Found no significant difference between 6-month abstinence rates for nicotine patch v. e-cigarette.
  • Authors expressed concern around findings due to small number of trials, low event rates, wide confidence intervals around mean.

Gómez-Coronado N, Walker AJ, Berk M, Dodd S. Current and Emerging Pharmacotherapies for Cessation of Tobacco Smoking. Pharmacotherapy. 2018;38(2):235-258. doi:10.1002/phar.2073

Kalkhoran S, Benowitz NL, Rigotti NA. Prevention and Treatment of Tobacco Use: JACC Health Promotion Series. J Am Coll Cardiol. 2018;72(9):1030-1045. doi:10.1016/j.jacc.2018.06.036