Smoking Cessation in Peripheral Artery Disease

Peripheral artery disease (PAD) is a common condition, and is associated with significant morbidity and mortality. Smoking is a key, modifiable risk factor for all manifestations of atherosclerotic cardiovascular disease (CVD), especially PAD. In fact, up to 80% of patients with PAD are current or former smokers.1 Tobacco cessation counseling is an important first step in the treatment of PAD, particularly because quitting smoking may improve claudication symptoms.2 Meanwhile, continuing to smoke is associated with a higher risk of disease progression, graft failure, amputation, restenosis after endovascular revascularization, myocardial infarction (MI), and death.3,4

Patients with PAD are often uniquely motivated to quit smoking when equipped with the knowledge that their claudication symptoms may improve, and that the need for invasive treatment and/or long-term medications can be reduced by quitting. Given the overwhelming benefit of smoking cessation in patients with PAD, and the opportunity of a motivated patient population, vascular medicine specialists are well-positioned to lead the clinical team in smoking cessation efforts. Treating physicians and clinical teams should develop skills to align evidence-based pharmacologic treatment and behavioral support with individual patient needs.

Tips & Framework

The 2018 American College of Cardiology decision pathway on tobacco cessation treatment is an excellent resource for clinicians caring for patients with CVD.5 Figure 1 summarizes the ideal approach:

Figure 1: Pathway for Tobacco Cessation Treatment5

Figure 1

The "5 A's" framework (Ask, Assess, Advise, Assist, Arrange) can help teams engage in effective counseling. Given the limited time and resources at each medical visit, more recently, the focused "AAC" model (Ask-Advise-Connect) has shown improved uptake of services by patients.6

  1. Ask - Ask all patients about smoking status (any nicotine use, whether daily or non-daily) at every clinical encounter. Include cigarettes as well as cigars, cigarillos, e-cigarettes, vape pens, flavored tobacco products, and water pipe or hookah use. Improve consistency with a systematic approach to asking about smoking habits within the clinic site. Patients may not consider themselves "smokers," despite regular use of tobacco products.
  2. Assess - If a patient reports any smoking or tobacco use, assess the amount, frequency, and type. In particular, assess the number of cigarettes per day, and the time to first cigarette after waking up. Assess for any previous quit attempts and any boosts, barriers, or motivating factors to those attempts. Is the patient ready to make a quit attempt?
  3. Advise - Regardless of readiness to quit, provide a clear, strong, and personalized message to patients who smoke, advising them to quit. In patients with PAD, this statement can be tailored to include claudication symptoms, disease progression or regression linked with smoking status, and the opportunity to reduce the risk of both amputation and MI.
  4. Assist - Offer both behavioral support and pharmacologic therapy. If ready to quit within the next 30 days, assist the patient in setting a quit date. Educate the patient on available resources, such as statewide Quitlines. Make note of patient preferences.
  5. Arrange / Connect - If the patient accepts the recommended therapy, provide appropriate prescriptions and referrals, and ensure follow-up with a member of the clinical team (whether in person or by phone) within 2-4 weeks. Evaluate response to treatment and any barriers, including potential adverse reactions. If the patient declines therapy, re-evaluate and reiterate the recommendation to quit at subsequent clinical encounters. In the Ask-Advise-Connect model, the name and contact information of patients who agree to be 'connected' are provided to the Quitline; those patients are then contacted proactively within 48 hours.

The available resources, staff, and systems, as well as patient needs at a given office visit will help guide the depth of tobacco cessation therapy delivered at the point of care. Because effective treatment is often a team-based and long-term effort, these simple steps may be useful:

  1. Keep smoking on the problem list. Especially in patients with CVD and multiple or severe medical problems, tobacco use can be lost or relegated to lower priority in busy clinic sessions. Add current or former smoking to the patient's problem list in the shared electronic medical record (EMR). Alerting physicians and care team members to the problem provides a reminder to screen and an opportunity to counsel at encounters across specialties.
  2. Provide out-of-clinic education. Keep high-quality, patient-facing education materials on hand in clinic to provide at visits. Keep in mind patients' health literacy and reading level. The Society for Vascular Medicine (SVM) journal Vascular Medicine publishes peer-reviewed 'patient information pages' free of cost (online at, including one on smoking cessation and one on electronic cigarettes.7,8

Pharmacologic Therapy

Successful tobacco cessation treatment generally combines behavioral counseling with pharmacologic therapy. While the selections for both should be tailored to patient needs and preferences, the key message is that the potential benefits of tobacco cessation treatment far outweigh any risks, especially in patients with PAD.

Effective pharmacologic treatment options for smoking cessation include nicotine replacement therapy (NRT), bupropion, and varenicline, all of which are FDA-approved and considered safe in patients with CVD.5 A reasonable first-line approach for most patients with PAD would be either combination ("basal-bolus") NRT or varenicline.

Combination NRT includes a nicotine patch used at baseline plus a short-acting form of nicotine as needed; lozenges or gum tend to help with the oral behavioral element of smoking. NRT is often familiar to patients, but counseling on correct usage is important to maximize effectiveness, while minimizing adverse reactions. For example, patients should be instructed on the "chew-and-park" method for nicotine gum and the importance of rotating nicotine patch sites daily to avoid skin irritation. NRT is typically initiated on the morning of the quit date, with application of the nicotine patch. Tapering the dose is optional, and may not be of particular benefit. Consider creating a "dot phrase" or stored instructions in the EMR to provide patients with quick pearls on medication use in their printed after-visit summaries.

Bupropion in certain formulations may be helpful as an added therapy to combination NRT. Patients with depression or low activation may especially benefit from this serotonin-norepinephrine reuptake inhibitor (SNRI), though it should be used with caution in patients at risk for seizure. Both bupropion and the nicotine patch were found in clinical trials to be more effective than placebo.9

Varenicline is the most effective pharmacologic option for smoking cessation. Multiple clinical trials have found varenicline to be more effective than patch-only NRT, bupropion alone, and placebo.9 As a partial agonist of alpha-4-beta-2 nicotinic acetylcholine receptors, varenicline relieves withdrawal symptoms while also reducing further nicotine binding to curb the satisfying sensation of smoking. Varenicline is typically started a week prior to the quit date, though even among patients who are not immediately ready to set a quit date, varenicline may increase quit rates.10

Initial concerns regarding varenicline's psychiatric effects may have caused reluctance of clinicians and patients to choose this treatment modality. Of note, the EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study) trial addressed these concerns. EAGLES (n=8,144) found that, relative to the nicotine patch or placebo, there was no increase in neuropsychiatric adverse events with varenicline or bupropion.9 Therefore, the FDA removed the black-box warning for the psychiatric side effects of varenicline in 2016.

The bottom line is that the benefits of quitting far outweigh any treatment-associated risks.3 Pharmacologic therapy should be offered at every visit, because smoking cessation offers such substantial benefit to patients with PAD.

Behavioral Therapy

Motivational interviewing is the cornerstone of behavioral therapy. Referral to a tobacco cessation coach, if available, can help patients address motivations and barriers to quitting over time, and can help patients prepare for their quit date. Referral to a resource such as 1-800-QUIT-NOW or provides accessible extensions of counseling and self-management services without requiring additional clinic visits. The National Cancer Institute (NCI) operates 1-800-QUIT-NOW, which ultimately connects users to their local Quitline services. States vary in services offered via Quitlines, with some providing free NRT. offers web- and text-based platforms, as well as resources tailored to specific populations. Evidence suggests that a clinical referral results in greater patient engagement than simply alerting patients to available resources.

Group support sessions for tobacco cessation are available through many health systems, providing a community for patients to share successes and challenges and to maintain efforts to quit. Encouraging patients to seek out and spend time in smoke-free settings and to enlist the support of family, friends, and coworkers may reduce the risk of relapse. Smoking is commonly comorbid with psychiatric conditions. Addressing any underlying anxiety or depression, particularly in conditions such as PAD that may be associated with pain and functional limitation, is important to success in improving vascular and overall health. In these situations, psychiatric therapy can become a key element of treatment in PAD.

While most tobacco cessation efforts take place in the outpatient setting, hospitalization of patients with PAD is an opportunity to highlight the importance of quitting and the unique motivators. Inpatient stays can be a time to explore and reinforce a patient's motivations to quit, such as the health and safety of family members, financial savings, avoidance of PAD progression requiring additional intervention, and reducing the risk of other cardiovascular events.


Tobacco cessation is paramount in the prevention and treatment of CVD in all its forms, including PAD. As cardiovascular clinicians, we can provide this essential component of PAD care by leveraging team-based medicine, keeping smoking at the top of the clinical priority list, and addressing the problem with evidence-based pharmacologic treatment and behavioral therapy at every visit.


  1. Smith GD, Shipley MJ, Rose G. Intermittent claudication, heart disease risk factors, and mortality. The Whitehall Study. Circulation 1990;82:1925-31.
  2. Ratchford EV. Medical management of claudication. J Vasc Surg 2017;66:275-80.
  3. Ratchford EV, Black JH 3rd. Approach to smoking cessation in the patient with vascular disease. Curr Treat Options Cardiovasc Med 2011;13:91-102.
  4. Willigendael EM, Teijink JAW, Bartelink ML, Peters RJG, Büller HR, Prins MH. Smoking and the patency of lower extremity bypass grafts: a meta-analysis. J Vasc Surg 2005;42:67-74.
  5. Barua RS, Rigotti NA, Benowitz NL, et al. 2018 ACC Expert Consensus Decision Pathway on Tobacco Cessation Treatment: A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2018;72:3332-65.
  6. Vidrine JI, Shete S, Cao Y, et al. Ask-Advise-Connect: a new approach to smoking treatment delivery in health care settings. JAMA Intern Med 2013;173:458-464.
  7. Ratchford EV, Evans NS. Smoking cessation. Vasc Med 2016;21:477-79.
  8. Blaha MJ, Ratchford EV. Electronic cigarettes. Vasc Med 2019;24:267-69.
  9. Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet 2016;387:2507-20.
  10. Ebbert JO, Hughes JR, West RJ, et al. Effect of varenicline on smoking cessation through smoking reduction. JAMA 2015;313:687-94.

Clinical Topics: Arrhythmias and Clinical EP, Cardiovascular Care Team, Dyslipidemia, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Statins, Smoking

Keywords: Aneurysm, Acetylcholine, Ambulatory Care, Amputation, Anxiety, Bupropion, Cardiovascular Diseases, Depression, Counseling, Disease Progression, Drug Labeling, Electronic Health Records, Electronic Nicotine Delivery Systems, Health Literacy, Follow-Up Studies, Friends, Hospitalization, Inpatients, Motivational Interviewing, Myocardial Infarction, Motivation, Nicotine, National Cancer Institute (U.S.), National Cancer Institute (U.S.), Norepinephrine, Office Visits, Outpatients, Pain, Patient Care, Patient Participation, Patient Preference, Peripheral Arterial Disease, Point-of-Care Systems, Receptors, Nicotinic, Recurrence, Referral and Consultation, Risk Factors, Seizures, Sensation, Serotonin, Smoking, Smoking Cessation, Smoke, Specialization, Substance Withdrawal Syndrome, Support Vector Machine, Tobacco, Tobacco Products, Tobacco Use Cessation, Tobacco Use, Treatment Outcome

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