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CLINICAL STATEMENTS AND GUIDELINES June 11, 2024 Circulation. 2024;149:e1313–e1410. DOI: 10.1161/CIR.0000000000001251 e1342 amputation.12 Although no single antihypertensive medication appears to be more effective at treating hypertension in patients with PAD, cardiovascular benefits are shown with the use of ACE inhibitors or angiotensin-receptor blockers, and these agents should be first line for patients with PAD and hypertension. 5.4 Smoking Cessation for PAD Recommendations for Smoking Cessation for PAD Referenced studies that support the recommendations are summarized in the Online Data Supplement. COR LOE Recommendations 1 A 1 Patients with PAD who smoke cigarettes or use any other forms of tobacco should be advised at every visit to quit or encouraged to maintain cessation.1–3 1 A 2 Patients with PAD who smoke cigarettes or use any other forms of tobacco should be assisted in developing a plan for quitting that includes pharmacotherapy (ie, varenicline, bupropion, and/or nicotine replacement therapies) combined with counseling, and/or referral to a smoking cessation program.4–9 1 B-NR 3 Patients with PAD should be advised to avoid exposure to secondhand tobacco smoke in all indoor or enclosed spaces, including work, home, transportation vehicles, and public places.10–14 Synopsis Cigarette smoking and other forms of tobacco use are strong, dose-responsive risk factors for PAD development.15–17 Quitting smoking and other forms of tobacco is important for reducing the risk of developing PAD, the progression of established PAD, and the risk of limb-related events and death. The continual encouragement by health care professionals of those they are treating for PAD is important in the process of quitting and sustaining smoking cessation. Both pharmacological and behavioral-based strategies, alone or in combination, increase the cessation rate in those with PAD.4,6,18 However, these strategies are underutilized. In addition to quitting, the avoidance of secondhand smoke is recommended to reduce MACE in those with established PAD. The use of electronic nicotine delivery systems should be discouraged in general and discouraged as a transitional tool from cigarettes to smoking cessation, because data are inadequate on the potential health effects.19 Recommendation-Specific Supportive Text 1 Overall, in the United States, 68% of adult smokers want to quit, 55% report attempting to quit, but only 7% are successful. Sparse direct evidence exists regarding the association of electronic nicotine delivery systems and cannabis for the development and progression of PAD.20 Long-term water pipe use (ie, hookah) increases risk factors associated with PAD and CAD.21 Observational studies suggest that smoking cessation is associated with lower rates of MALE, including bypass graft failure and amputation, as well as death in patients with PAD.22–25 The risk of PAD development remains >2 times higher than that of never-smokers for up to 10 to 20 years after quitting and does not return to the risk of a nonsmoker until after 30 years after quitting.17 Clinician advice and encouragement increase cessation rates, which supports simple provider-based measures as a component of smoking cessation programs.1–3 2 Coordinated smoking cessation interventions that combine nonpharmacological and pharmacological approaches can increase cessation rates by 2 to 3 times that of self-quit attempts.10 An RCT of a follow-up program and smoking cessation medications provided to hospitalized patients, including those with PAD, showed a modest increase in cessation rates.6,18 Pharmacotherapy is more effective when combined with counseling.26–28 In an RCT of patients with PAD, a comprehensive smoking cessation program combining counseling and pharmacological agents increased the rates of smoking cessation to 21%, compared with 7% with standard advice alone.4 Three US Food and Drug Administration (FDA)-approved pharmacological approaches (ie, varenicline, bupropion, and nicotine replacement therapy) used alone or in combination all increase smoking cessation rates.3,5,7 Two metaanalyses of RCTs of smoking cessation medications showed no evidence of increase in MACE with nicotine replacement, bupropion, or varenicline.8,9 Emerging data have demonstrated that electronic nicotine delivery systems have a positive effect on smoking cessation rates.29–31 However, long-term health-related outcomes (MACE and MALE) with use of electronic nicotine delivery systems have not been evaluated.3 Additional clinical investigation of electronic nicotine delivery systems in patients with PAD is needed to establish their safety and efficacy for smoking cessation in this patient population. Despite multiple available tools, smoking cessa- tion support strategies are underutilized among patients with PAD.32 Clinicians caring for patients with PAD should include smoking cessation in the treatment plan and prescribe therapy based on current guidelines, including a 2018 ACC expert consensus decision pathway.33 3 Secondhand smoke contains nicotine, fine particu- lates, and toxic chemicals, and is associated with an increased risk of all-cause death, stroke, and CVD.10–12 Moderate-quality evidence has associated secondhand smoke exposure with the development of PAD.13,14 Emissions from electronic Downloaded from http://ahajournals.org by on October 7, 2026