Peripheral Artery Disease (PAD) of Lower Extremities

Background

• PAD of lower extremities refers to the stenosis, occlusion, or aneurysmal dilation of lower-extremity arterial branches characterized by a range of presentations including asymptomatic disease, intermittent claudication, ischemic rest pain, and ulceration/gangrene of the lower extremities.
• Cigarette smoking and diabetes are the strongest risk factors; additional important risk factors include diabetes, hypertension, dyslipidemia, and advanced age.
• Peripheral artery disease with an ankle-brachial index [ABI] < 0.9 is associated with an increased risk of cardiovascular death, all-cause mortality, coronary heart disease, and stroke.

Evaluation

• For patients at risk for PAD, perform vascular exam and obtain comprehensive medical history and review of symptoms to assess for exertional leg symptoms, ischemic rest pain, and nonhealing wounds (Strong recommendation).
• Measure the ABI if lower-extremity PAD is suspected by history and/or physical exam and if any of the following are present: exertional leg symptoms, nonhealing wounds, ischemic leg pain at rest, age ≥ 65 years, or age ≥ 50 years with history of smoking or diabetes (Strong recommendation).
• Consider measuring the ABI in patients at increased risk of PAD but without history or physical examination findings suggestive of PAD (Weak recommendation).
• An ABI:
  • ≤ 0.9 confirms the diagnosis of PAD
  • 0.91-0.99 is borderline
  • 1.0-1.4 is normal
  • > 1.4 indicates a noncompressible artery
• Measure the toe-brachial index (TBI) to diagnose patients with suspected PAD when a noncompressible artery (ABI > 1.4) is present (Strong recommendation); a TBI ≤ 0.7 is diagnostic of PAD.
• Perform exercise treadmill ABI testing to evaluate for PAD in patients with exertional non-joint-related leg symptoms and a normal or borderline resting ABI (> 0.9 and ≤ 1.4) (Strong recommendation).
• Consider measurement of an exercise ABI in patients who are at risk for lower-extremity PAD but have a normal ABI and do not have classic claudication symptoms or other clinical evidence of atherosclerosis (Weak recommendation).
• Tests to identify the location and extent of disease may include Doppler and duplex ultrasound, magnetic resonance imaging, computed tomography angiography, and pulse volume recording.
• Use leg segmental pressure measurements when anatomic localization of PAD is needed to guide a therapeutic plan (Strong recommendation).
• The exercise treadmill test or 6-minute walk test can provide objective assessment of functional status in those with known PAD.

Management

• For all patients with atherosclerotic lower-extremity PAD, including asymptomatic patients:
  • Tobacco use:
    • Advise for cessation of smoking or any other forms of tobacco (if patient uses tobacco) at every visit (Strong recommendation).
    • Assist in developing a plan for quitting tobacco that includes pharmacotherapy (such as, varenicline, bupropion, and/or nicotine replacement therapy) and/or referral to a smoking cessation program (Strong recommendation).
    • Avoid passive smoke exposure at work, home, and in public places (Strong recommendation).
  • Use antiplatelet therapy to reduce the risk of myocardial infarction, stroke, or vascular death if the patient is symptomatic (Strong recommendation) and consider it if the patient is asymptomatic (Weak recommendation).
    • Recommended drugs are aspirin 75-325 mg/day or clopidogrel 75 mg once daily (Strong recommendation).
  • Guidelines differ on the use of dual antiplatelet therapy (combination of aspirin and clopidogrel) for some revascularized patients:
    • suggested by American College of Cardiology/American Heart Association (ACC/AHA) for patients with symptomatic PAD after lower extremity revascularization (Weak recommendation)
    • suggested by Society for Vascular Surgery for patients having infrainguinal endovascular intervention for claudication (duration ≥ 30 days) or as an alternative to antiplatelet monotherapy in patients having lower extremity venous or prosthetic bypass (Weak recommendation)
    • suggested by American College of Chest Physicians (ACCP) for patients having below-knee bypass graft surgery with prosthetic grafts (duration 1 year) (Weak recommendation)
  • The overall clinical benefit of vorapaxar added to existing antiplatelet therapy in patients with symptomatic PAD is uncertain.
• Treat cardiovascular risk factors including hyperlipidemia, hypertension, and diabetes (Strong recommendation).
  • Give a statin to all patients with PAD (Strong recommendation).
  • Give antihypertensive therapy to patients with hypertension and PAD to reduce the risk of myocardial infarction, stroke, heart failure, and cardiovascular death (Strong recommendation).
  • Consider angiotensin-converting enzyme inhibitors or an angiotensin-receptor blocker to reduce the risk of cardiovascular ischemic events in patients with PAD (Weak recommendation).
  • Coordinate the management of diabetes mellitus in patients with PAD between members of the healthcare team (Strong recommendation), and counsel patients with diabetes about self–foot examination and healthy foot behaviors (Strong recommendation).
  • Consider using a PCSK9 inhibitor in patients with PAD that are statin intolerant or on the maximally tolerated dose of a statin with suboptimal low-density lipoprotein (LDL) cholesterol (LDL-C ≥ 70 mg/dL).
• For patients with claudication:
  • Advise supervised exercise therapy (at least 30-45 minutes ≥ 3 times/week for ≥ 12 weeks) to improve functional status and quality of life and to reduce leg symptoms in patients with claudication (Strong recommendation).
  • Consider structured community- or home-based exercise program with behavioral change techniques to improve functional status and walking ability in patients with PAD (Weak recommendation).
  • Medical therapy:
    • Cilostazol 100 mg orally twice daily is recommended for improving symptoms and increasing walking distance in patients with claudication by the ACC/AHA (Strong recommendation), and is suggested as add-on therapy in patients with claudication not responding to exercise therapy and smoking cessation by the ACCP (Weak recommendation).
    • Medical therapies NOT recommended or suggested by all professional organizations in patients with claudication include:
      • prostanoids by the ACC/AHA (Strong recommendation) and by the ACCP (Weak recommendation)
      • chelation therapy (for example, ethylene diamine tetraacetic acid [EDTA]) and B-complex vitamins by the ACC/AHA (Strong recommendation)
      • pentoxifylline not recommended by the ACC/AHA (Strong recommendation) and by the ACCP (Weak recommendation, but has weak recommendation to support use by SVS (Weak recommendation).
  • Revascularization:
    • Endovascular procedures are an effective revascularization option for patients with hemodynamically significant aortoiliac occlusive disease (AIOD) and lifestyle-limiting claudication (Strong recommendation).
    • Revascularization is a reasonable treatment option for patients with lifestyle-limiting claudication with an inadequate response to guideline-directed management and therapy (Weak recommendation).
    • When surgical revascularization is performed, bypass to the popliteal artery with an autogenous vein graft is recommended in preference to prosthetic graft material (Strong recommendation).
    • Bypass surgery and angioplasty may have similar efficacy for chronic lower limb ischemia.
    • The addition of endovascular revascularization to supervised exercise increases the pain-free walking distance in patients with PAD and stable claudication.
  • Intermittent compression of the calf may improve the pain-free walking distance.
• Follow-up:
  • Clinically evaluate patients with PAD periodically, including assessment of cardiovascular risk factors, limb symptoms, and functional status (Strong recommendation).
  • Clinically evaluate and perform ankle-brachial index measurement periodically in patients with PAD who have had lower extremity revascularization (surgical and/or endovascular) (Strong recommendation).
  • Counsel patients with PAD and diabetes mellitus about self–foot examination and healthy foot behaviors (Strong recommendation).
• For management of critical limb ischemia including acute limb ischemia, see Management of Acute and Critical Limb Ischemia.