CHAPTER 31: PREVENTING AND MITIGATING SMOKING-RELATED HEART DISEASE

The reductions in cigarette smoking prevalence over the second half of the 20th century and beginning of the 21st century represent one of the major medical and public health advancements of this time. Decreases in smoking rates, in conjunction with improvement in treatment of other cardiovascular risk factors, such high cholesterol and blood pressure, and advancements in the treatment of heart disease, have contributed to substantial declines in rates of death from heart disease.^1,2 Despite this progress, tobacco use remains a major preventable cause of morbidity and mortality worldwide. Both active smoking and passive exposure to secondhand smoke increase the risk of cardiovascular disease, malignancy, and pulmonary diseases. As a result, effective strategies for reducing health risks from smoking should address both smoking cessation and reduction of exposure to secondhand smoke.

Smoking cessation is an important component of both primary prevention and secondary prevention of cardiovascular disease. Despite this and the US Public Health Service recommendation that all patients be asked about their tobacco use status on a regular basis,³ tobacco use screening occurs in only two-thirds of outpatient physician office visits.⁴ Even though 69% of smokers are interested in quitting and over half report having made a quit attempt in the past year,⁵ only 21% of adult current tobacco users received tobacco cessation counseling and 8% received tobacco cessation medication during outpatient visits.⁴ This situation highlights the importance of screening by health professionals to capture individuals interested in tobacco cessation and assist them in quitting. This screening is particularly important because physician advice to quit smoking is associated with increased smoking cessation compared to no advice to quit or usual care, with higher cessation seen with more intensive advice compared to minimal advice.⁶ Interventions led by other members of the health care team, such as nurses, have also been associated with increased smoking cessation.⁷ It is important that screening be incorporated into all clinical encounters, including by cardiologists and other specialists, not only to identify and assist patients who are ready to stop smoking, but also to encourage those who are not yet ready to move toward making the decision to quit.

Overall and Cardiovascular Benefits of Smoking Cessation

The risk of overall mortality is greatly reduced for patients who quit smoking.^8,9 Smoking cessation before the age of 30 years eliminates nearly all of the risk of death from smoking-related disease, and even those who quit when they are older gain years of life compared to those who continue to smoke.^10,11 This fact highlights both the importance of encouraging smokers to quit early as well as encouraging quitting among all smokers, no matter how old they are.

In addition to contributing to long-term development of atherosclerosis, smoking (and secondhand smoke exposure) has immediate effects (within minutes) on endothelial function^12,13 and platelet activation,⁹ and so can trigger a cardiac event. The risk of cardiac events begins to drop immediately after quitting and declines rapidly. The heart rate drops 20 minutes after quitting, and in a year, half the excess risk of a myocardial infarction is gone.¹⁴ The risk of myocardial infarction and other cardiac events drops 15% to 20% by a month after implementing comprehensive smoke-free laws to protect people from secondhand smoke.^15,16 Smoking cessation should be used as a first-line therapy for people with heart disease.

Among patients with coronary heart disease, a systematic review of 20 studies found an overall 36% reduction in risk of mortality among those who quit smoking compared to those who continued to smoke.¹⁷ A meta-analysis of 12 cohort studies found that the odds of death after myocardial infarction was nearly halved among those who quit smoking compared to those who continued smoking,¹⁸ and one study found that the risk of repeat coronary events in patients who quit smoking after their first myocardial infarction decreased to that of nonsmokers 3 years after cessation.¹⁹ In patients with a previous myocardial infarction or stable angina followed for a mean of 8 years, risk of sudden cardiac death was significantly increased in current smokers compared to those who had never smoked, while there was no significant difference between former smokers and “never” smokers.²⁰ In patients with left ventricular dysfunction, quitting smoking was associated with decreased morbidity and mortality within 2 years.²¹ Such improvements are comparable to benefits from treatment with medications such as beta-blockers or angiotensin-converting enzyme inhibitors.²²

Screening for Tobacco Use

The US Public Health Service recommends the “5As” model for smoking cessation intervention, in which providers (1) ask patients about tobacco use to identify current users, (2) advise tobacco users to quit, (3) assess patient interest in and willingness to quit, (4) assist patients interested in quitting with counseling and/or pharmacotherapy, and (5) arrange for follow-up to monitor progress (Fig. 31–1). Although current smokers report high rates of being asked about tobacco use (88%), fewer report being advised to quit (66%), and even fewer being asked if they wanted to quit (43%).²³ If smokers are not properly identified, those interested in cessation cannot be connected with resources that can help them with their quit attempt. Therefore, screening should be incorporated into all outpatient and hospital encounters.

Adequate follow-up with patients interested in quitting is important for prevention of relapse. Although most relapse to smoking occurs within the first week of quitting,²⁴ relapse does occur in those who have been abstinent from cigarettes for much longer periods of time,²⁵ making it important to monitor patients for at least 6 months after they quit.

Treatment for Smoking Cessation

Both pharmacotherapy and counseling are effective treatments for smoking cessation, with success highest when they are combined.²⁶ Such a combination of methods can address both a smoker’s physical addiction to nicotine (by managing withdrawal symptoms) as well as the habit of smoking. Symptoms of nicotine withdrawal include cravings, as well as a number of nonspecific symptoms including irritability, depressed mood, restlessness, sleep disturbance, trouble concentrating, and increased appetite. Withdrawal symptoms have a variable time course, with resolution within 10 days in some²⁷ but longer in others,²⁸ particularly for cravings, which can persist for over 6 months after quitting.²⁵

Pharmacologic Therapy for Smoking Cessation

Various prescription and nonprescription medications approved by the US Food and Drug Administration (FDA) are available to assist patients in their quit attempt, provided patients do not have contraindications to their use.³ This includes nicotine replacement therapy (NRT), varenicline, and bupropion (Table 31–1). They are all first-line treatments for smoking cessation, and choice of agent should take into consideration patient preferences, medical comorbidities, and potential drug-drug interactions.

Nicotine Replacement Therapy

Nicotine is the addictive drug in cigarettes and other tobacco products, and nicotine withdrawal is what triggers many of the symptoms smokers suffer after quitting. NRT, which provides patients with nicotine to manage cravings and nicotine withdrawal symptoms, comes in a variety of forms. Types of NRT include patches, gum, lozenges, inhalers, and nasal sprays. The nicotine patch is a long-acting form of nicotine replacement with a slow onset of action, providing a steady dose of nicotine throughout the day, whereas the gum, lozenge, inhaler, and nasal spray are short-acting forms of replacement that provide more rapid relief of cravings and withdrawal symptoms. Each type of NRT is associated with significantly increased smoking cessation compared to control (either placebo or no NRT), and use of a combination of NRT products (ie, use of a nicotine patch in conjunction with a short-acting form of nicotine) is associated with increased smoking cessation compared to a single type of NRT.²⁹ Therefore, for highest efficacy, the nicotine patch should be combined with a short-acting form of NRT.

With respect to treatment duration, a randomized clinical trial of different durations of nicotine patch treatment (8, 24, or 52 weeks) found higher rates of smoking abstinence at 24 weeks in those still using nicotine patches, but no significant difference was seen at 52 weeks.³⁰ This result suggests that, while nicotine patch treatment can continue longer than 8 to 10 weeks, evidence does not support extending treatment past 24 weeks. For timing of treatment initiation, there is some evidence that starting nicotine patches prior to a patient’s quit day is associated with increased smoking cessation compared to starting after the quit day. However, no difference was seen with nicotine gum or lozenges.²⁹ Thus, it is not necessary to wait until the quit date to initiate treatment with nicotine patches.

It is important to note that, while clinical trials have demonstrated efficacy of NRT when used as part of an organized cessation effort, unsupervised NRT bought over the counter is associated with significantly less quitting than use of no smoking cessation aids (odds ratio [OR] 0.68, confidence interval [CI] 0.49-0.94).³¹ Thus, patients using NRT should be followed and encouraged to maintain their quit attempt. Such combinations of counseling and NRT can be accomplished through telephone quitlines, which also provide certain types of NRT to eligible callers.

A network meta-analysis of 21 randomized controlled trials found an increase in all cardiovascular disease events (relative risk [RR] 2.29, 95% CI 1.39-3.82) with NRT compared to placebo, but no significant difference in major adverse cardiovascular events (RR 1.95, CI 0.92-4.30).³² In one study of patients who had acute coronary syndrome, there was no significant difference in death, myocardial infarction, repeat revascularization, or rehospitalization for angina, congestive heart failure, or arrhythmia after one year in those who received NRT compared to those who did not.³³ In any event, the risks associated with NRT are much lower than the risks of continued smoking.

Varenicline

Varenicline is a partial nicotinic receptor agonist that is taken daily by mouth, starting the week prior to a patient’s quit date and continuing for a total of 12 weeks. Varenicline is associated with two to three times higher odds of smoking cessation compared to placebo,³⁴ and extension of varenicline treatment for an additional 12 weeks has also been associated with increased continuous abstinence from cigarettes.³⁵ Thus, treatment can be continued for a total of 6 months. A 2015 randomized controlled trial of varenicline for smoking cessation among patients hospitalized with acute coronary syndrome found higher point prevalence of smoking abstinence at 24 weeks in those taking varenicline compared to placebo (47.3% vs 32.5%, P = .012) and higher continuous abstinence rates (35.8% vs 25.8%, P = .05).³⁶

Varenicline has a number of safety concerns, including a boxed warning for serious neuropsychiatric events, such as agitation, hostility, depressed mood, changes in behavior or thinking, and suicidal ideation or behavior. A 2015 systematic review and meta-analysis of 39 randomized controlled trials found no significant increase in suicide or attempted suicide, suicidal ideation, depression irritability, aggression, or death in those taking varenicline compared to those taking placebo.³⁷ Additionally, a retrospective cohort study of 164,766 patients in England found a decrease in depression and self-harm in patients taking varenicline compared with those taking NRT.³⁸ Nevertheless, patients should be closely monitored after initiation of varenicline for onset of neuropsychiatric events.

Studies on the cardiovascular safety of varenicline have yielded mixed results. A network meta-analysis of 18 randomized controlled trials comparing varenicline versus placebo found no significant difference in all cardiovascular disease events (RR 1.30, 95% CI 0.79-2.23) or major adverse cardiovascular events (RR 1.34, CI 0.66-2.66),³² while another meta-analysis reported an increase in serious adverse cardiovascular events in those using varenicline (Peto OR 1.72, 95% CI 1.09-2.71).³⁹ One possible explanation for the difference in results of these two studies is the statistical approach (random effects meta-analysis vs Peto method). In a third meta-analysis conducted by the FDA, no statistically significant increase in major adverse cardiac events within 30 days of discontinuation of varenicline treatment versus placebo was found (hazard ratio [HR] 1.96, 95% CI 0.79-4.82).⁴⁰ In this study, the overall incidence of major adverse cardiovascular events was low in both the varenicline group (0.31%) and the placebo group (0.21%).

Bupropion

Bupropion is approved both for the treatment of depression and for smoking cessation. It is started a week prior to a smoker’s quit date and continued for 7 to 12 weeks. Bupropion was associated with greater smoking cessation than placebo/control in a recent meta-analysis.⁴¹ However, whether this is true in all patient populations is unclear. A study of smokers hospitalized with acute myocardial infarction found that although bupropion was well tolerated, it did not increase smoking cessation compared to placebo.⁴²

Like varenicline, bupropion carries a boxed warning for neuropsychiatric reactions and suicidal thoughts and behaviors. A meta-analysis of 33 trials found (1) increased incidence of serious adverse events (defined as a life-threatening event; an event leading to hospitalization, death, disability, or permanent damage; or an event requiring intervention to prevent such an outcome) in individuals treated with bupropion compared to control (RR 1.30, 95% CI 1.00-1.69) and (2) no significant increase in psychiatric serious adverse events (RR 0.60, 95% CI 0.28-1.28).⁴¹ A network meta-analysis found no significant difference associated with bupropion treatment versus placebo in cardiovascular disease events and significantly decreased major adverse cardiovascular events in those treated with bupropion.³²

Combination Therapy

As discussed above, treatment with a combination of long-acting and short-acting NRT is associated with increased smoking cessation compared to a single type of NRT.²⁹ A randomized controlled trial found that varenicline combined with NRT was associated with higher tobacco abstinence at 12 weeks and 6 months compared to varenicline alone.⁴³ Another randomized controlled trial found that treatment with both varenicline and bupropion for 12 weeks was associated with significantly greater smoking cessation than treatment with varenicline alone at 12 weeks (OR 1.49, 95% CI 1.05-2.12) and 26 weeks (OR 1.52, 95% CI 1.04-2.22)—but not at 52 weeks (OR, 1.32, 95% CI 0.91-1.91).⁴⁴ Participants receiving combination therapy, however, reported more anxiety and depressive symptoms. Combination bupropion and NRT treatment is not associated with a significant difference in smoking cessation compared to NRT alone.⁴¹ While combining different forms of NRT is a recommended, effective strategy for smoking cessation, combination of NRT with bupropion has not proven to be effective, and while combination varenicline and NRT has shown some promise of efficacy at 6 months, further studies on long-term efficacy and safety are needed.

Other Pharmacotherapy

Other medications, although not FDA-approved for smoking cessation in the United States, have been studied for smoking cessation. Nortriptyline, a tricyclic antidepressant, has been associated with increased smoking cessation compared to placebo.⁴¹ However, given the association between tricyclic antidepressants and cardiac disease, this drug should be avoided in patients with underlying heart disease. Clonidine, an α²-agonist, has been shown in a meta-analysis of six studies to be associated with significantly increased smoking cessation. However, only one of the individual trials had a statistically significant result.³⁴ Cytisine, a nicotine receptor partial agonist, has been associated with increased smoking cessation compared to placebo in combined results from two trials.³⁴ Although it is marketed in some European countries, it is not currently approved for smoking cessation in the United States.

Behavioral Interventions and Other Therapies for Smoking Cessation

Counseling delivered by telephone, either through telephone quitlines or other sources, is also associated with smoking cessation,⁴⁵ as are some mobile phone–based interventions,⁴⁶ printed self-help materials,⁴⁷ and interactive, tailored Internet-based interventions.⁴⁸ Motivational interviewing, which consists of counseling to improve an individual’s motivation to, and interest in, undergoing behavioral change, has also been associated with increased smoking cessation compared to brief advice or usual care.⁴⁹ In individuals using pharmacotherapy for smoking cessation, the addition of behavioral support through in-person or telephone contact is also associated with increased smoking cessation compared to control groups.⁵⁰Assistance via telephone is available from state telephone quitlines toll-free at 1-800-QUIT-NOW (1-800-784-8669). Support through text messaging can also be found through the National Cancer Institute’s Smokefree TXT program, which is available at smokefree.gov/smokefreetxt, or by texting the word QUIT to 47848 from a mobile phone.

Acupuncture, acupressure, or laser therapy has not been associated with long-term smoking cessation compared with sham interventions.⁵¹ Studies on hypnotherapy for smoking cessation, either compared to no intervention or other interventions, have not found a consistent long-term benefit.⁵²

Health Effects of Smoking Reduction

Cigarette smoking, even at low levels, is associated with an increased risk of cardiovascular disease.^53,54,55 The dose-response relationship between smoking and cardiovascular disease is highly nonlinear, with more rapid increases in risk at low levels of exposure and flattening of the curve at higher levels of exposure.⁵³ In fact, smoking as few as five cigarettes a day is associated with higher risk of death from ischemic heart disease.⁵⁵ Smoking a few cigarettes a day should not be promoted as a long-term use pattern, and complete cessation should be encouraged in all patients.

Smoking reduction has been associated with improved levels of biomarkers associated with cardiovascular disease in some studies^56,57 but not in others.⁵⁸ It is not clear whether improvements in these biomarkers also results in improvements in risk of smoking-related disease. Statistically significant improvement in systolic and diastolic blood pressure and heart rate have been seen with smoking reduction,⁵⁷ but a randomized controlled trial of smoking reduction found no difference in angina, quality of life, or adverse events in those assigned to the reduction group.⁵⁸ A study in Denmark found that although there was a decreased risk of myocardial infarction among individuals who had stopped smoking (HR 0.71, 95% CI 0.59-0.85), smoking reduction by at least 50% had no significant association with myocardial infarction (HR 1.15, 95% CI 0.94-1.40).⁵⁹

Smokers should be encouraged to quit cigarettes entirely, particularly because smoking even a few cigarettes still carries significant increased cardiovascular risks compared to quitting cigarettes altogether.

Exposure to secondhand smoke significantly increases the risk of myocardial infarction and other cardiac events. Indeed, heart disease accounts for about 90% of all secondhand smoke–attributable deaths.¹⁶ All patients should be instructed to make their homes smoke-free and avoid exposure to secondhand smoke. Doing so not only reduces exposure to smoke and the associated health risks, but smoke-free homes also facilitate smoking cessation.

Laws making workplaces and restaurants and bars smoke-free covered half of the US population in 2015.⁶⁰ Several meta-analyses have evaluated the impact of smoke-free laws on hospitalization for cardiovascular disease.^15,61,62,63 The most recent of these meta-analyses,⁶² which included 31 studies with estimates for 47 locations, found an overall 12% reduction in hospitalizations for acute coronary events (RR 0.88, 95% CI 0.85-0.90) after implementation of smoke-free laws. Greater reductions were seen for locations with comprehensive legislation (workplaces, restaurants, and bars) compared to partial legislation (14% for comprehensive vs 8% for partial). Studies have also found reduction in mortality from cardiovascular disease after implementation of smoke-free laws.^64,65,66,67 A meta-analysis of the association between smoke-free legislation and hospital admission for cerebrovascular accidents found a 19% decrease in hospitalizations following implementation of comprehensive smoke-free laws (RR 0.81, 95% CI 0.70-0.94; five studies).¹⁵ A study found a 32% reduction in stroke mortality (RR 0.68, 95% CI 0.54-0.85) in Ireland after implementation of a national ban on smoking in workplaces; this mortality reduction was seen only for those age 65 and older.⁶⁷ Furthermore, a decrease in calls to ambulances was seen after implementation of a smoke-free law in Colorado.⁶⁸ This evidence that smoke-free laws reduce cardiovascular disease events highlights the importance of asking nonsmokers, especially those with cardiovascular disease, about secondhand smoke exposure and give strong advice to have smoke-free homes and automobiles if they do not already, which extends the protection of laws into their home environment.

In addition to the benefits of smoke-free laws and policies for reducing secondhand smoke exposure in workplaces, public places, and homes, these regulations have also been associated with increased smoking cessation and decreased cigarette consumption among current smokers^69,70 and with increases in voluntary smoke-free laws in homes and cars.⁷¹ Smoke-free laws promote both increased protection from secondhand smoke and decreased active smoking.

There is great variability in the prevalence of cigarette smoking worldwide. Although tobacco control policies have played a substantial role in reducing smoking prevalence in places such as the United States and United Kingdom, smoking rates remain high in many parts of the world, particularly among men. For example, over half of men in Indonesia, Russia, and China currently smoke,⁷² compared to fewer than 19% of men in the United States.⁷³ The World Health Organization’s Framework Convention on Tobacco Control (FCTC), the first global public health treaty, adopted in 2003 and implemented in 2005, emphasizes the importance of promoting public health through implementation of policies, including smoke-free environments to protect people from secondhand smoke and provide an environment that helps people stop smoking; elimination of tobacco advertising and promotion; increased taxes to reduce demand for cigarettes; and education of the public on the risks of smoking, such as with large graphic warning labels on tobacco products.⁷⁴ Although the FCTC has accelerated implementation of smoke-free laws⁷⁵ and strong health warning labels,⁷⁶ only about half of nations report 100% smoke-free restaurants and even fewer in private workplaces.⁷⁷ As of 2016, the United States was one of the few countries that had not ratified the FCTC, and the United States lags behind the rest of the world in several areas, notably strong graphic warning labels on tobacco products, restrictions on advertising and promotion, and tobacco taxation. More comprehensive smoking laws are needed worldwide to ensure the maximum health benefits conferred to both smokers and nonsmokers by such tobacco control legislation.

Electronic cigarettes (e-cigarettes), a type of electronic nicotine delivery systems, are battery-powered devices that heat a solution of humectants such as propylene glycol or glycerol, generally with nicotine and/or flavorings, to form an aerosol that is inhaled by the user. E-cigarettes are relatively new products, so their long-term health effects are unknown. Additionally, as of January 2016, e-cigarettes were not regulated by the FDA. Although many smokers report using e-cigarettes to quit smoking, randomized controlled trials on efficacy for smoking cessation have been limited and their results have been equivocal.^78,79 As currently being used in the real world, e-cigarettes are associated with significantly less quitting than NRT or no cessation aids.⁸⁰ Data from three studies^81,82,83 suggest that specific e-cigarette use patterns (daily use of high nicotine delivery devices, which represents the minority of users in these studies) may be associated with increased quitting; as e-cigarette product types and use patterns continue to evolve, this association should continue to be studied. Nevertheless, e-cigarettes should not be recommended as effective smoking cessation aids until there is evidence that, as promoted and used, they assist smoking cessation.^80,84

A policy statement by the American Heart Association in 2014 encourages the inclusion of e-cigarette use in tobacco screening questions.⁸⁵ Use of e-cigarettes by patients may signal readiness to quit cigarettes, and thus clinicians should be prepared to support patients in their quit attempts and to discuss evidence-based practices for smoking cessation, including counseling, NRT, or stop-smoking pharmacotherapy, with these patients.⁸⁴

Clinicians should screen all patients for use of tobacco products and exposure to secondhand smoke. Once patients who use tobacco are identified, they should be advised to quit and educated about the various health benefits of quitting, which begin to develop soon after abstinence. Patients should be guided to evidence-based resources to assist them in their quit attempts, including both counseling (either from clinicians themselves or through resources such as in-person tobacco counselors, telephone counselors through state quitlines, or mobile-based counseling through text messaging) and medications. Follow-up with patients should occur shortly after a plan for cessation is established—to ensure that the patients are not having problems with obtaining medications or counseling support; that they are not experiencing any side effects from treatment; and to provide continued support and encouragement, particularly soon after the quit attempt, when risk of relapse is highest.

Cigarette smoking remains a major cause of cardiovascular and all-cause mortality. The risk of smoking-induced cardiovascular diseases decreases soon after smoking cessation regardless of how old people are when they quit. Counseling and pharmacotherapy are both effective aids for smoking cessation, and their combination is more effective than either alone. Comprehensive smoke-free policies both protect nonsmokers from secondhand smoke exposure and encourage smoking cessation and implementation of smoke-free homes among current smokers, which, in turn, not only protects people from exposure to secondhand smoke but supports cessation.

Smoking cessation should be considered an important therapeutic intervention for people with heart disease and implemented as part of routine clinical care for these patients.