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:
		- 2nd line.
- Meta-analysis demonstrates benefit over placebo but non-significant benefit over bupropion; no benefit as adjunct medication to NRT.
 
 
- Nicotine replacement therapy (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.
 
| Medication | Mechanism | Dosing | Side Effects | Available OTC? | 
|---|---|---|---|---|
| Nicotine patch | Controlled nicotine dose | >10 cigarettes/day: 21 mg qday <10 cigarettes/day: 14 mg qday Taper after 6 weeks, but can be continued as long as patient would like | Irritation at patch site, sleep disturbance | Yes | 
| Nicotine gum | Controlled dose of nicotine | 1st cigarette of day <30 minutes after waking; 4 mg q1-2h 1st cigarette of day >30 minutes after waking: 2 mg q1-2h | Oral issues, nausea, heartburn, hiccups | Yes | 
| Nicotine lozenge | Controlled dose of nicotine | 1st cigarette of day <30 minutes after waking; 4 mg q1-2h 1st cigarette of day >30 minutes after waking: 2 mg q1-2h | Oral issues, nausea, heartburn, hiccups | Yes | 
| Nicotine inhaler | Controlled dose of nicotine | 10 mg cartridge 6-16x/day | Oropharyngeal irritation, cough | No | 
| Nicotine nasal spray | Controlled dose of nicotine | 1-2 spray per nostril q1h | Nasopharyngeal irritation, sneezing, cough | No | 
| Varenicline | Partial nicotinic receptor agonist | 0.5 mg qday for 3 days, then 0.5 mg BID for 4 days, then 1 mg BID | Nausea, abnormal dreams | No | 
| Bupropion | Increases levels of norepinephrine and dopamine, may act as nicotine receptor antagonist | 150 mg qday for 3 days, then 150 mg BID | Insomnia, dry mouth; contra-indicated if seizure disorder | No | 
| Nortriptyline (2nd line) | Increases norepinephrine levels, inhibits noradrenergic reuptake, decreased neuronal firing in locus coeruleus | 25 mg qday, titrate to 75-100 mg qday; start therapy 10-28 days before “quit date,” and continue >12 weeks post “quit date” | Drowsiness, dizziness, dry mouth, blurred vision, constipation, weight gain, trouble urinating | No | 
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