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Subject: Peripheral Arterial Disease
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Predominant age: >40 years
Predominant sex: male > female (2:1), based on the Framingham study
Patients with symptomatic PAD have a 5-year mortality rate of 30%.
Highly prevalent syndrome that affects 8 to 12 million individuals in the United States
U.S. prevalence: 2.7 to 4.1%
Age-adjusted prevalence of PAD is close to 12%.
Up to 29% among patients in primary care practices
In patients with PAD, arterial stenoses cause inadequate blood flow in distal limbs, which fails to meet the metabolic demand during exertion:
Most common cause of arterial stenoses is atherosclerosis.
Age >40 years
See “Risk Factors.”
Associated with other common complications of atherosclerosis, including myocardial infarction (MI), transient ischemic attack (TIA), stroke, and limb amputation
Occurs in ∽40% of patients with cardiovascular disease
Intermittent claudication, with symptoms typically resolving within 2 to 5 minutes of rest (although it is regarded as the classic symptom for PAD, intermittent claudication is present in only 10% of patients with PAD)
Rest leg pain (especially in a supine position)
Skin ulceration (in advanced PAD)
Gangrene (in advanced PAD)
Skin pallor when leg is elevated above the level of the heart (in mild PAD)
Dry and scaly skin
Poor nail growth
Reduced/absent extremity pulses (in advanced PAD)
Deep venous thrombosis
Thromboangiitis obliterans (Buerger disease)
Restless legs syndrome
Spinal stenoses (pseudoclaudication)
Intervertebral disc prolapse
Fasting lipid profile is indicated for risk assessment of hyperlipidemia.
Duplex ultrasonography and Doppler color-flow imaging, which are useful in detecting stenosed segments and assessing lesion severity, are initial imaging tests of choice.
Magnetic resonance angiography, coupled with 3D reconstruction, is highly sensitive and specific for the localization of occluded lesions.
CT scanning has a limited role in the evaluation of PAD.
Angiography remains the gold standard in the diagnosis of PAD.
Doppler ABI measures the ratio of the higher systolic BPs between the dorsalis pedis and the posterior tibial artery versus the higher of the systolic BPs in the two brachial arteries: Values for the ABI should be reported as “incompressible” if >1.40, “normal” if 1.00 to 1.40, “borderline” if 0.91 to 0.99, and “abnormal” if ≤0.90. ABI ≪0.4: severe ischemia
Segmental limb pressures: usually obtained if abnormal ABI measurement is identified; a ≤20-mm Hg reduction in pressure is considered significant for PAD.
Treadmill exercise test assesses the severity of claudication and the response to treatment.
Segmental volume plethysmography: often used in conjunction with segmental limb pressures to measure the volume changes in an organ or limb; the study is indicated for calcified vessel when the ABI cannot be applied diagnostically.
Claudication exercise rehabilitation program: patient to walk until symptoms develop, then rest and start again, for a total of 30 minutes initially; walking then is increased by 5 minutes until 50 minutes of intermittent walking is achieved.
Modification of risk factors, including smoking cessation, diabetes mellitus, hypertension, and hyperlipidemia:
The effect of aspirin on the risk reduction of overall ischemic events is inconclusive. Some suggest that aspirin delays disease progression and reduces the need for surgical intervention. AHA/ACCF guidelines 1[A] note that the use of antiplatelet therapy to reduce cardiovascular risks in asymptomatic patients with borderline ABIs is characterized as “not well-established.” Aspirin is recommended to reduce the risk of MI, stroke, and vascular death in symptomatic patients with PAD.
Low-dose aspirin (75 to 150 mg/day) is as effective as higher doses of aspirin.
Clopidogrel (75 mg/day) is approved by the FDA for the secondary prevention of thrombotic events in patients with symptomatic lower extremity PAD and is recommended as an alternative to aspirin.
Vorapaxar (Zontivity) 2.08 mg PO daily is a platelet aggregation inhibitor different in mechanism from existing antiplatelet drugs (TRAP inhibitor). It is contraindicated if history of CVA, TIA, or intracranial hemorrhage; concern for bleeding risk; and is expensive
Other medications that may improve symptoms of claudication include pentoxifylline (1.2 g/day), cilostazol (100 mg BID), and naftidrofuryl (600 mg/day).
Neither vasodilators nor anticoagulant therapy (e.g., heparin, low-molecular-weight heparin, or oral anticoagulant) has shown any clinically proven efficacy for the treatment of claudication and may be harmful.
Cilostazol (100 mg BID) improves walking distance in people with intermittent claudication secondary to PAD. There is currently insufficient data on whether taking cilostazol results in a reduction of all-cause mortality and cardiovascular events or an improvement in quality of life 2[A].
Other medications that may reduce claudication include pentoxifylline (1.2 g/day), naftidrofuryl (600 mg/day), and prostaglandins (120 μg/day). Ticlopidine (250 mg BID) reduces the risk of MI, stroke, and death in patients with PAD, but it has a complication of thrombocytopenia in 2-3% of patients.
Weight reduction, smoking cessation, and BP control are essential in treating claudication.
Exercise programs are of significant benefit compared with placebo or usual care in improving walking time and distance in people with leg pain from intermittent claudication who were considered to be fit for exercise intervention 3[A]. A walking program should include walking at least 3 times per week for 30 to 60 minutes each time and has been shown to improve quality of life as much as or more so than medication.
A healthy diet high in complex carbohydrates (e.g., whole grains and pastas), fruits and vegetables, and low in salt and animal fats
Transluminal balloon angioplasty is a percutaneous method of dilating arterial stenoses or recanalizing occluded vessels with or without stents (reserved for short, isolated, and hemodynamically significant lesions of the iliac or proximal superficial femoral artery).
Bypass surgery is the standard operative treatment for lower extremity peripheral occlusive disease.
Acupuncture, biofeedback, chelation therapy, and supplements such as Ginkgo biloba, omega-3 fatty acids, and vitamin E have been studied.
Ginkgo biloba modestly reduces the symptoms of intermittent claudication (120 mg/day for up to 6 months) and can be considered as an adjunct to exercise therapy. Inconclusive evidence exists for the use of vitamin E.
An exercise training program composed of walking/bicycle riding improves maximal treadmill walking distance and, therefore, enhances functional capacity.
However, little added benefit exists from Ginkgo biloba treatment when added to supervised exercise training in patients with PAD as compared with patients in exercise training program alone.
Among patients with intermittent claudication, 15-20% will experience worsening claudication; 5-10% will undergo lower extremity bypass surgery; and 2-5% will need primary amputation (rates for smokers and diabetics are much higher).
30,000 to 50,000 people in the United States undergo amputations annually because of PAD.
Duprez DA. Pharmacological interventions for peripheral artery disease. Expert Opin Pharmacother. 2007;8(10):1465–1477.
Gey DC, Lesho EP, Manngold J. Management of peripheral arterial disease. Am Fam Physician. 2004;69(3):525–532.
Hankey GJ, Norman PE, Eikelboom JW. Medical treatment of peripheral arterial disease. JAMA. 2006;295(5):547–553.
Hiatt WR, Hirsch AT, Creager MA, et al. Effect of niacin ER/lovastatin on claudication symptoms in patients with peripheral artery disease. Vasc Med. 2010;15(3):171–179.
Wang J, Zhou S, Bronks R, et al. Supervised exercise training combined with ginkgo biloba treatment for patients with peripheral arterial disease. Clin Rehabil. 2007;21(7):579–586.
I73.9 Peripheral vascular disease, unspecified
I70.209 Unsp athscl native arteries of extremities, unsp extremity
I70.219 Athscl native arteries of extrm w intrmt claud, unsp extrm
I70.229 Athscl native arteries of extrm w rest pain, unsp extremity
I70.299 Oth athscl native arteries of extremities, unsp extremity
443.9 Peripheral vascular disease, unspecified
440.20 Atherosclerosis of native arteries of the extremities, unspecified
440.21 Atherosclerosis of native arteries of the extremities with intermittent claudication
440.22 Atherosclerosis of native arteries of the extremities with rest pain
440.23 Atherosclerosis of native arteries of the extremities with ulceration
440.24 Atherosclerosis of native arteries of the extremities with gangrene
440.29 Other atherosclerosis of native arteries of the extremities
399957001 Peripheral arterial occlusive disease (disorder)
51274000 Atherosclerosis of arteries of the extremities
63491006 Intermittent claudication (disorder)
Screening of a general medical population for PAD is not recommended. Studies have indicated that screening for PAD among asymptomatic adults in the general population could lead to false-positive results and unnecessary workups. The prevalence among the general public who are asymptomatic is low.
A patient already receiving medical treatment should be referred for further surgical evaluation for any of the following scenarios:
The clopidogrel (75 mg/day) versus aspirin (325 mg/day) study in the patients at risk of ischemic events (CAPRIE) trial found a 23.8% relative risk ratio for MI, stroke, or cardiovascular death in PAD patients treated with clopidogrel compared with aspirin but no statistically significant difference in overall mortality reduction. Clopidogrel is much more expensive than aspirin.