Smoking Cessation: Pharmacotherapy and Cardiovascular Benefit

Definition and cardiovascular rationale

Smoking cessation is the complete discontinuation of tobacco smoking, with avoidance of second-hand smoke and, where possible, other inhaled nicotine products. In cardiovascular medicine, the objective is not merely to reduce cigarette consumption but to achieve complete abstinence from tobacco and ultimately from nicotine.

Smoking is a major modifiable driver of atherosclerosis and cardiovascular disease. Its relationship with cardiovascular risk is nonlinear: even light smoking carries a substantial proportion of the excess ischaemic heart disease risk associated with heavy smoking. Consequently, reducing the number of cigarettes smoked does not produce a proportional reduction in cardiovascular harm. Complete cessation is therefore the preferred therapeutic endpoint.

The cardiovascular benefits of cessation extend across primary and secondary prevention. Observational evidence indicates that cessation lowers the risk of peripheral artery disease, myocardial infarction, premature death, recurrent infarction and limb-threatening complications. Among patients with established peripheral artery disease, those who stop smoking have approximately twice the five-year survival of those who continue. After acute coronary syndrome, tobacco abstinence has been associated with reductions in reinfarction of approximately 30–40% and in death of approximately 35–45%. In chronic coronary syndrome, cessation has been associated with a 36% reduction in premature mortality compared with continued smoking.

Cessation also improves vascular health and may reduce cardiovascular risk within several years, although risk may remain higher than that of never-smokers for a prolonged period. In heavy smokers, cardiovascular risk falls within five years of stopping but may remain elevated thereafter. The overall health benefit is greater still when reductions in non-cardiovascular morbidity and mortality are included.

Clinical presentation and assessment

Identifying tobacco exposure

Every cardiovascular assessment should establish:

• Current smoking status.

• Cigarettes smoked per day.

• Duration of smoking and cumulative exposure.

• Previous quit attempts and their duration.

• Triggers for smoking and anticipated barriers to cessation.

• Exposure to second-hand smoke.

• Use of cannabis, electronic cigarettes or other inhaled products.

• Readiness to attempt cessation.

• Depression, schizophrenia, schizoaffective disorder, HIV infection or other circumstances that may affect cessation or treatment monitoring.

Single-question screening can identify unhealthy drug use requiring counselling regarding cardiovascular effects and potential drug interactions. Cannabis should also be addressed, particularly in patients with established atherosclerotic disease.

Readiness and behavioural context

A brief, structured intervention should be used whenever smoking is identified. During encounters with smokers, “very brief advice” can initiate discussion and promote referral to formal cessation support. More intensive, individualized counselling is more effective than advice alone, although long-term success rates remain modest and repeated intervention is often necessary.

Patients with acute coronary syndrome should be offered cessation support during hospitalization. Depression and adverse environmental exposures are associated with continued or resumed smoking after the acute event and warrant particular attention.

Cardiovascular benefits of cessation

The principal benefits relevant to clinical cardiology include:

An average weight gain of approximately 5 kg may occur after cessation. This should be addressed, but the cardiovascular hazard of continued smoking is greater than the cardiovascular risk associated with this weight gain.

Pharmacotherapy

Pharmacotherapy should be considered for smokers who are ready to stop, particularly when advice, encouragement and motivation alone are insufficient. Medication is most effective when combined with behavioural support.

Nicotine-replacement therapy

Nicotine-replacement therapy provides nicotine without tobacco combustion products and is available in several formulations:

• Chewing gum.

• Transdermal patches.

• Lozenges or sublingual tablets.

• Nasal spray.

• Inhaler.

All forms of nicotine-replacement therapy are effective in supporting cessation. Combining different nicotine-replacement products may improve efficacy compared with a single formulation. Practical selection should account for craving pattern, patient preference, ability to use the device correctly and adherence.

Nicotine-replacement therapy, bupropion and varenicline have not been associated with an increase in major adverse cardiovascular events in patients with chronic coronary syndromes. In acute coronary syndrome, nicotine-replacement therapy can be considered as part of an inpatient cessation programme alongside counselling and behavioural interventions.

The source material does not provide specific nicotine doses, patch strengths or duration schedules.

Bupropion

Bupropion is an antidepressant used to reduce withdrawal symptoms and support long-term cessation. It is effective at a level similar to nicotine-replacement therapy in the cited guideline material. It may be used with behavioural support and can be considered in patients with established atherosclerotic disease or after acute coronary syndrome.

In people with schizophrenia or schizoaffective disorder, available evidence supports the safety and efficacy of bupropion and does not indicate a serious safety signal; nevertheless, mental health should be monitored because nicotine abstinence itself may be associated with deterioration in mental health.

The source material does not provide a bupropion dose, treatment duration or contraindication list.

Varenicline

Varenicline acts at nicotinic receptors and reduces craving. It is described as the most effective medical treatment for smoking cessation in the acute coronary syndrome setting and is considered safe for use in such patients. In comparative data, varenicline achieved higher quit rates than bupropion or nicotine patches, and each active treatment was more effective than placebo.

Varenicline can be used in patients with atherosclerotic cardiovascular disease, including those with chronic coronary disease and acute coronary syndrome. Evidence in people with schizophrenia and schizoaffective disorder supports its efficacy and does not identify a serious safety signal, but careful follow-up is appropriate in patients with previous mental health problems.

The source material does not provide a varenicline dose or treatment duration.

Combination treatment

Cessation success may be improved by:

• Combining pharmacotherapy with behavioural intervention.

• Combining different nicotine-replacement formulations.

• Combining medication with counselling delivered in person, by telephone, text messaging or internet-based programmes.

• Maintaining behavioural and pharmacological treatment to reduce relapse risk.

In patients with serious mental illness, continued treatment has been reported to reduce relapse. Smoking cessation may also alter the metabolism of psychotropic medication: tobacco smoke induces CYP1A2, and stopping smoking can therefore increase plasma concentrations of drugs such as clozapine. Dose adjustment should be undertaken in consultation with the treating psychiatrist.

Potential interactions between antiretroviral therapy and cessation medication have not been adequately studied. Small studies of varenicline, bupropion and nicotine-replacement therapy in people living with HIV have generally shown safety and success rates similar to those reported in people without HIV, but treatment should still be individualized.

Behavioural and non-pharmacological management

Pharmacotherapy should be embedded within a structured cessation programme. Effective approaches include:

• Individual counselling.

• Group therapy and support groups.

• Motivational enhancement.

• Personalized feedback.

• Telephone-based counselling.

• Text messaging and internet-based programmes.

• Mobile applications offering monitoring, motivation and personalized plans.

• Stress-management techniques such as mindfulness, meditation and breathing exercises.

• Regular physical activity.

• A balanced diet and adequate sleep.

Intensive group therapy may substantially increase quit rates in people living with HIV, although the absolute rates remain low and durability varies between studies. In people with schizophrenia, brief behavioural interventions based on motivational enhancement and personalized feedback increase engagement with nicotine-dependence treatment compared with psychoeducation alone.

Counselling should be repeated over time because cessation programmes commonly have low efficacy at 12 months, and relapse is frequent even after an initially successful quit attempt.

Electronic cigarettes

Electronic cigarettes are not harmless and should not be considered equivalent to cessation. Their effects on cardiovascular health remain a concern. Reported adverse effects include increased arterial stiffness, heart rate and blood pressure, endothelial dysfunction and other unfavourable vascular changes. Long-term outcome data remain inadequate.

Guideline positions in the source material differ in emphasis. Some guidance discourages routine use because electronic cigarettes are not harm-free and because evidence for durable tobacco abstinence is insufficient. Other guidance allows them to be considered briefly as an aid to stopping conventional cigarettes, preferably within a formal cessation programme and without concurrent smoking. They should not become a long-term substitute for tobacco abstinence or a route to dual use.

The clinical priority remains complete cessation of smoked tobacco and, ultimately, avoidance of all nicotine products where feasible.

Guideline-based treatment strategy

General cardiovascular disease

Smoking cessation is recommended as a central cardiovascular risk-reduction intervention. Patients should receive:

• Clear advice to stop smoking.

• Assessment of readiness and barriers.

• Behavioural counselling or referral to a cessation programme.

• Pharmacotherapy when appropriate.

• Repeated follow-up to support abstinence and prevent relapse.

• Advice to avoid passive smoking.

Chronic coronary syndrome and atherosclerotic disease

All smokers who are prepared to quit should be offered pharmacological support. Nicotine-replacement therapy, bupropion and varenicline are effective options and are not linked to increased major adverse cardiovascular events in the cited guidance.

Acute coronary syndrome

Intervention should begin during hospitalization and combine:

• Behavioural intervention.

• Counselling.

• Pharmacotherapy.

• Post-discharge follow-up.

Varenicline is identified as the most effective medical treatment in this setting and is considered safe for patients with acute coronary syndrome. Nicotine-replacement therapy and bupropion are also options.

Peripheral artery disease and polyarterial disease

Complete smoking cessation and avoidance of second-hand smoke are particularly important because continued smoking is associated with disease progression, chronic limb-threatening ischaemia, amputation and death. Structural follow-up support should include nicotine-replacement therapy, varenicline and bupropion, used individually or in combination when appropriate.

Diabetes and cardiovascular disease

Smoking cessation is a key lifestyle intervention in people with type 2 diabetes, with or without cardiovascular disease. In cardiovascular disease, the cited evidence suggests a 36% reduction in mortality. Pharmacotherapy should be introduced early when advice and motivation are insufficient.

Serious mental illness

The same first-line cessation pharmacotherapies used in the general population can be used in people with schizophrenia or schizoaffective disorder, alongside behavioural therapy. Patients with previous mental health problems require careful follow-up because nicotine withdrawal and the cessation process may adversely affect mental health. Medication levels may change after cessation because of reversal of tobacco-smoke CYP1A2 induction; psychotropic doses may therefore need adjustment.

Preoperative cardiovascular risk reduction

Smoking cessation before non-cardiac surgery reduces postoperative complications. The clearest benefit is seen when cessation occurs more than four weeks before surgery, with further improvement associated with each additional week of cessation. Cessation should therefore be addressed as early as possible during preoperative assessment.

Practical clinical pathway

A concise clinical pathway is:

At every encounter

• Document tobacco use and second-hand exposure.

• Advise complete cessation.

• Assess readiness and previous experience.

• Offer referral and pharmacotherapy.

At the quit attempt

• Select nicotine-replacement therapy, bupropion or varenicline according to clinical circumstances and patient preference.

• Add individualized behavioural support.

• Explain that weight gain may occur but is less harmful than continued smoking.

• Establish early follow-up.

During follow-up

• Confirm abstinence and identify relapse risk.

• Reinforce avoidance of passive smoke and dual use.

• Reassess mood and mental health where relevant.

• Review adherence and adverse effects.

• In patients taking CYP1A2-substrate psychotropics, consider whether smoking cessation has increased drug exposure and coordinate dose review with psychiatry.

• Repeat intervention if relapse occurs rather than considering relapse a treatment failure.

Prognosis and follow-up

Smoking cessation improves prognosis in both primary and secondary cardiovascular prevention. Benefits include lower cardiovascular mortality, fewer recurrent coronary events, reduced progression of peripheral artery disease and fewer limb-threatening outcomes. The effect is clinically meaningful even in heavy smokers and at older ages.

Risk does not immediately become equivalent to that of a never-smoker. In particular, excess peripheral artery disease and cardiovascular risk may persist for many years after cessation. This should be communicated without weakening the message that stopping remains highly beneficial.

Follow-up should be structured and repeated because initial success does not guarantee sustained abstinence. Continued behavioural and pharmacological support reduces relapse, particularly in patients with serious mental illness. Cardiovascular care should continue to address other modifiable risk factors, including physical inactivity, obesity, dyslipidaemia, diabetes, hypertension and excessive alcohol intake, as smoking cessation is most effective when incorporated into comprehensive cardiovascular prevention.