Impact of Tobacco Smoking and Smoking Cessation on Cardiovascular Risk and Disease

Christopher Bullen


Expert Rev Cardiovasc Ther. 2008;6(6):883-895. 

In This Article


Recent advances have occurred in the pharmacologic treatment of tobacco dependence, and numerous pharmacotherapies now exist.[113] The most widely used treatment is nicotine replacement therapy (NRT) but newer, highly targeted treatments, such as vareniciline, are becoming more widely available.

Nicotine Replacement Therapy

Tobacco cessation typically causes nicotine withdrawal symptoms such as irritability, anxiety and hunger in many patients.[114] The use of pharmacotherapies, which provide direct nicotine replacement, is a logical approach to try to reduce these negative effects. NRT is well-established in smoking cessation and includes a wide range of delivery systems including gum, transdermal patch, nasal spray, inhaler and lozenge.[115] However, none of the NRT products currently available delivers nicotine at the same speed or dose as delivered by cigarettes. Nevertheless, all NRT products are of proven and approximately equivalent efficacy, improving the likelihood of long-term abstinence compared with placebo by 50–170% (ORs range from 1.5 to 2.7).[110,115,116]

Nicotine replacement therapy is just as effective in patients with cardiovascular disease as in those without. Nevertheless, many clinicians have been reluctant to provide NRT to such patients because of concerns over safety.[117] This fear should now be put to rest once and for all. Using any form of NRT, including combinations such as patch and gum, or patch and nasal spray, is far safer than continued smoking. The risks, even for those with severe cardiovascular disease, are small and are far outweighed by the benefits of smoking cessation.[48] As discussed, nicotine has known cardiovascular effects but clinical trials of NRT in patients with underlying, stable coronary disease indicate that NRT does not increase cardiovascular risk.[117] Even when NRT is used while still smoking, the effects are similar to those of cigarette smoking alone because the dose–cardiovascular response curve for nicotine is flat.[117]

In situations where patients are acutely ill, oral, shorter-acting forms of NRT (gum or lozenge, for example) have often been favoured by clinicians in preference to transdermal patches. The rationale has been that in the event of a crisis, nicotine levels are able to reduce more rapidly.[118] However, a recent study of smokers with acute coronary syndrome who received patches found no increase in short- or long-term mortality compared with a matched sample who did not use patches.[119] On this basis, NRT should be offered to all smokers with cardiovascular disease[117] with only very few provisos and precautions ( Box 1 ).[117,120,121,201] These recommendations go further than the manufacturer's instructions, which tend to be very conservative.


Bupropion, initially promoted as an antidepressant treatment, was the first non-NRT treatment for smoking dependence shown to be effective. Bupropion doubles the likelihood of abstinence over placebo and is more effective than the nicotine patch.[122] Bupropion's efficacy in smoking cessation is unrelated to its antidepressant effects. While its precise mechanism of action is unknown, it is likely to be related to inhibition of dopamine and/or noradrenaline neural reuptake. The most common side effects are insomnia and dry mouth.[123] Bupropion appears to be safe in patients with cardiovascular disease,[124] although doseage reduction may be needed when patients are taking Type 1c antiarrhythmics.[125]


Varenicline is a partial agonist at the α4β2 nicotinic acetylcholine receptor, where the dependency-causing properties of nicotine are mediated.[126] As a partial agonist, varenicline relieves withdrawal symptoms and cravings while, as an antagonist, it blocks the reinforcing effects of nicotine. Varenicline is more efficacious than both placebo and bupropion in clinical trials.[125] In a randomized, double-blind, placebo-controlled trial, the odds of quitting smoking with varenicline were significantly greater than the odds of quitting with either placebo (OR: 3.85) or slow-release bupropion (OR: 1.90).[126] Varenicline has few interactions and appears to be safe to use in patients with cardiovascular disease.[127,128] However, recent reports of neuropsychiatric problems such as depressed mood, suicidal ideation, attempted or completed suicide, erratic behavior and agitation in some patients using varenicline for cessation may limit its use.[129]

Other Pharmacotherapies

Other less commonly used pharmacotherapies for smoking cessation include clonidine, nortryptiline, SSRI antidepressants and anxiolytics. There is insufficient evidence to support or refute the use of SSRIs and anxiolytics[130] but clonidine and nortryptiline are effective and relatively inexpensive. However, their role in smoking cessation is limited due to side effects[125,130] and there are precautions in patients with cardiovascular disease. Nortryptiline in particular should be avoided in patients with a recent AMI or arrhythmia.[131]

Other Treatments

Despite widespread promotion of their effectiveness, there is currently insufficient evidence to support most other treatments available for tobacco smoking dependence. In particular, there is little evidence to support the use of acupuncture or hypnosis in smoking cessation.[132,133]


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