Peripheral Vascular Disease: Introduction 2. Risk factors for PVD include smoking, hyperlipidemia,
Background diabetes mellitus, and hyperviscosity.
Peripheral vascular disease (PVD) is a nearly pandemic 3. Other etiologies for developing PVD may include
condition that has the potential to cause loss of limb or even phlebitis, injury or surgery, and autoimmune disease,
loss of life. Peripheral vascular disease manifests as including vasculitides, arthritis, or coagulopathy.
insufficient tissue perfusion caused by existing PVD rarely exhibits an acute onset; it instead manifests a
atherosclerosis that may be acutely compounded by either more chronic progression of symptoms.
emboli or thrombi. Many people live daily with peripheral Patients with acute emboli causing limb ischemia may
vascular disease; however, in settings such as acute limb have new or chronic atrial fibrillation, valvular disease, or
ischemia, this pandemic disease can be life threatening and recent MI, whereas a history of claudication, rest pain, or
can require emergency intervention to minimize morbidity ulceration suggests thrombosis of existing PVD.
and mortality. Radiation-induced PAD is becoming more common,
Pathophysiology perhaps due to the efficacy of current antineoplastic
PVD, also known as arteriosclerosis obliterans, is primarily treatment and increased survival.
the result of atherosclerosis. The atheroma consists of a core 4. Intermittent claudication may be the sole manifestation
of cholesterol joined to proteins with a fibrous intravascular of early symptomatic PVD. The level of arterial
covering. The atherosclerotic process may gradually progress compromise and the location of the claudication are
to complete occlusion of medium and large arteries. The closely related as follows:
disease typically is segmental, with significant variation from Aortoiliac disease manifests as pain in the thigh and
patient to patient. buttock, whereas femoral-popliteal disease manifests as
Vascular disease may manifest acutely when thrombi, pain in the calf.
emboli, or acute trauma compromises perfusion. Symptoms are precipitated by walking a predictable
Thromboses are often of an atheromatous nature and occur distance and are relieved by rest.
in the lower extremities more frequently than in the upper Collateral circulation may develop, reducing the
extremities. Multiple factors predispose patients for symptoms of intermittent claudication, but failure to
thrombosis. These factors include sepsis, hypotension, low control precipitant factors and risk factors often causes
cardiac output, aneurysms, aortic dissection, bypass grafts, its reemergence.
and underlying atherosclerotic narrowing of the arterial Claudication may also present as the hip or leg "giving
lumen. out" after a certain period of exertion and may not
Emboli, the most common cause of sudden ischemia, usually demonstrate the typical symptom of pain on exertion.
are of cardiac origin (80%); they also can originate from The pain of claudication usually does not occur with
proximal atheroma, tumor, or foreign objects. Emboli tend to sitting or standing.
lodge at artery bifurcations or in areas where vessels 5. Ischemic rest pain is more worrisome; it refers to pain in
abruptly narrow. The femoral artery bifurcation is the most the extremity due to a combination of PVD and
common site (43%), followed by the iliac arteries (18%), the inadequate perfusion.
aorta (15%), and the popliteal arteries (15%). Ischemic rest pain often is exacerbated by poor cardiac
The site of occlusion, presence of collateral circulation, and output.
nature of the occlusion (thrombus or embolus) determine the
The condition is often partially or fully relieved by placing
severity of the acute manifestation. Emboli tend to carry
the extremity in a dependent position, so that perfusion
higher morbidity because the extremity has not had time to
is enhanced by the effects of gravity.
develop collateral circulation. Whether caused by embolus or
6. Leriche syndrome is a clinical syndrome described by
thrombus, occlusion results in both proximal and distal
intermittent claudication, impotence, and significantly
thrombus formation due to flow stagnation.
decreased or absent femoral pulses. This syndrome
indicates chronic peripheral arterial insufficiency due to
History narrowing of the distal aorta.
The primary factor for developing peripheral vascular disease 7. The patient's medications may provide a clue to the
(PVD) is atherosclerosis. existence of PVD.
1. Other maladies that often coexist with PVD are coronary Pentoxifylline is a commonly used medication specifically
artery disease (CAD), myocardial infarction (MI), atrial prescribed for PVD.
fibrillation, transient ischemic attack, stroke, and renal Daily aspirin commonly is used for prevention of cardiac
disease. Studies have suggested that even asymptomatic disease (CAD), but PVD often coexists, to some degree,
peripheral arterial disease (PAD) is associated with in patients with CAD.
increased CAD mortality.
Physical Deep Venous Trauma, Peripheral Vascular
A systematic examination of the peripheral vasculature is Thrombosis and Injuries
critical for proper evaluation. Thrombophlebitis
1. Peripheral signs of peripheral vascular disease are the Workup
classic "5 P's":
1. Routine blood tests generally are indicated in the
evaluation of patients with suspected serious
compromise of vascular flow to an extremity. CBC, BUN,
creatinine, and electrolytes studies help evaluate factors
that might lead to worsening of peripheral perfusion.
2. Paralysis and paraesthesia suggest limb-threatening
Risk factors for the development of vascular disease
ischemia and mandate prompt evaluation and
(lipid profile, coagulation tests) can also be evaluated,
although not necessarily in the ED setting.
3. Assess the heart for murmurs or other abnormalities.
2. An ECG may be obtained to look for evidence of
Investigate all peripheral vessels, including carotid,
dysrhythmia, chamber enlargement, or MI.
abdominal, and femoral, for pulse quality and bruit. Note
3. Elevated levels of inflammatory blood markers such as D
that the dorsalis pedis artery is absent in 5-8% of normal
dimer, C-reactive protein, interleukin 6, and
subjects, but the posterior tibial artery usually is present.
homocysteine have been linked to decreased lower
Both pulses are absent in only about 0.5% of patients.
extremity tolerance of exercise. Higher levels of activity
Exercise may cause the obliteration of these pulses.
in daily life have been shown to decrease these
4. The Allen test may provide information on the radial and
levels. The applicability to practice in Emergency
Medicine is unknown.
5. The skin may have an atrophic, shiny appearance and
may demonstrate trophic changes, including alopecia;
1. Plain films are of little use in the setting of PVD. Doppler
dry, scaly, or erythematous skin; chronic pigmentation
ultrasonographic studies are useful as primary
changes; and brittle nails.
noninvasive studies to determine flow status. Upper
6. Advanced PVD may manifest as mottling in a "fishnet
extremities are evaluated over the axillary, brachial,
pattern" (livedo reticularis), pulselessness, numbness, or
ulnar, and radial arteries. Lower extremities are
cyanosis. Paralysis may follow, and the extremity may
evaluated over the femoral, popliteal, dorsalis pedis, and
become cold; gangrene eventually may be seen. Poorly
posterior tibial arteries. Note the presence of Doppler
healing injuries or ulcers in the extremities help provide
signal and the quality of the signal (ie, monophasic,
evidence of preexisting PVD.
biphasic, triphasic). The presence of distal flow does not
7. The ankle-brachial index (ABI) can be measured at
exclude emboli or thrombi because collateral circulation
bedside. Using Doppler ultrasonography, the pressure at
may provide these findings.
the brachial artery and at the posterior tibialis artery is
2. Magnetic resonance imaging (MRI) may be of some
measured. The ankle systolic pressure is divided by the
clinical benefit due to its high visual detail. Plaques are
brachial pressure, both measured in the supine position.
imaged easily, as is the difference between vessel wall
Normally, the ratio is more than 1. In severe disease, it is
and flowing blood. MRI also has the benefits of
less than 0.5.
angiography to provide even higher detail and can
8. A semiquantitative assessment of the degree of pallor
replace traditional arteriography. The utility of MRI is
also may be helpful. While supine, the degree of pallor is
limited in the emergency setting, often due to location of
the device and the technical skill required to interpret
If pallor manifests when the extremity is level, the pallor
the highly detailed images.
is classified as level 4.
3. Computerized tomography (CT) can be of use to the
If not, the extremity is raised 60°. If pallor occurs within
emergency physician since it does not have the time and
30 seconds, it is a level 3; in less than 60 seconds, level 2;
availability constraints of MRI. Although noncontrast
in 60 seconds, level 1; and no pallor within 60 seconds,
studies can be useful to image calcification and
arteriosclerosis, contrast studies are most useful to
image arterial insufficiency. Renal function should be
Aneurysm, Abdominal Lumbar (Intervertebral) Disk confirmed before contrast administration, since PVD
Disorders often coexists with risk factors for contrast-induced renal
Ankle Injury, Soft Tissue Thrombophlebitis, Septic failure.
Back Pain, Mechanical Thrombophlebitis, Superficial
Other Tests in both dosage and time of administration. Remember that
1. The ankle-brachial index (ABI) is a useful test to compare intra-arterial thrombolysis remains investigational. Obviously,
pressures in the lower extremity to the upper extremity. such thrombolytic therapy is contraindicated in the presence
Blood pressure normally is slightly higher in the lower of active internal bleeding, intracranial bleeding, or bleeding
extremities than in the upper extremities. Comparison to at noncompressible sites.
the contralateral side may suggest the degree of Consultations
ischemia. Early surgical consultation in patients with acute limb
2. The ABI is obtained by applying blood pressure cuffs to ischemia is prudent. Depending on the case, the surgeon may
the calf and the upper arm. The blood pressure is involve interventional radiology or proceed operatively.
measured, and the systolic ankle pressure is divided by Emboli may be treated successfully by Fogarty catheter (ie,
the systolic brachial pressure. Normal ABI is more than 1; an intravascular catheter with a balloon at the tip). The
a value less than 0.95 is considered abnormal. This test balloon is passed distal to the lesion; the balloon is inflated,
can be influenced by arteriosclerosis and small vessel and the catheter is withdrawn along with the embolus. This
disease (eg, diabetes), reducing reliability. Progressive technique most commonly is used for iliac, femoral, or
PAD, indicated by ABI decline of greater than 0.15, has popliteal emboli.
been associated with increased cardiovascular disease Definitive treatment of hemodynamically significant
risk. aortoiliac disease is usually by aortobifemoral bypass. Its 5-
3. Transcutaneous oximetry affords assessment of impaired year patency rate is approximately 90%. Those patients in
flow secondary to both microvascular and macrovascular whom PVD becomes significant, however, often have a
disruption. Its use is increasing, especially in the realm of plethora of comorbid medical conditions, such as
wound care and patients with diabetes. Transcutaneous cardiovascular disease, diabetes, and chronic obstructive
oximetry has not been studied extensively in emergent pulmonary disease, which increase procedural morbidity and
occlusion. mortality. Axillobifemoral bypass and femoral-femoral bypass
Procedures are alternatives, both of which have lower 5-year patencies
The criterion standard for intraluminal obstruction has but have lower procedural mortality.
always been arteriography, although this is both potentially Some areas of arteriostenosis can be revascularized with
risky and often unobtainable in the emergency setting. The percutaneous transluminal coronary angioplasty (PTCA). If
delay associated with obtaining arteriography in the setting the occlusion is complete, a laser may be useful in making a
of obvious limb ischemia can delay definitive treatment to small hole through which to pass the balloon. Restenosis is a
deleterious effect. If time allows, arteriography can prove concern with PTCA, particularly for larger lesions. Stents and
useful in discriminating thrombotic disease from embolic lasers are still considered experimental.
disease. An initial study shows promise in relieving the pain of PAD
Treatment with topically applied lidocaine spray. Suzuki and colleagues
Prehospital Care studied 24 subjects with PAD and noted a significant drop in
Prehospital care for peripheral vascular disease (PVD) pain associated with PAD by applying an 8% lidocaine
involves the basics: control ABCs, obtain intravenous access, metered dose spray to the affected areas. Blood levels of
and administer oxygen. Generally, do not elevate the lidocaine were minimal, and this technique may show
extremity. Note and record distal pulses and skin condition. promise for those affected with focal PAD pain.
Perform and document a neurological examination of the Medication
affected extremities. The goal of pharmacotherapy is to reduce morbidity and to
Emergency Department Care prevent complications.
Attention to the ABCs, intravenous access, and obtaining Anticoagulants
baseline laboratory studies should occur early in the ED visit. Anticoagulants reduce thrombin generation and fibrin
Obtain an ECG and chest radiograph. formation and minimize clot propagation.
Treatment of either thrombi or emboli in the setting of Heparin
peripheral vascular disease is similar. Empirically, initiate a Augments activity of antithrombin III and prevents
heparin infusion with the goal of increasing activated partial conversion of fibrinogen to fibrin. Does not actively lyse but
thromboplastin time to 1.5 times normal levels. Acute leg is able to inhibit further thrombogenesis. Prevents
pain correlated with a cool distal extremity, diminished or reaccumulation of clot after spontaneous fibrinolysis.
absent distal pulses, and an ankle blood pressure less than 50 Adult
mm Hg should prompt consideration of emergent surgical 80 U/kg IV bolus, followed by infusion of 18 U/kg/h
In some cases of emboli, intra-arterial thrombolytic agents
may be useful. The exact technique of administration varies,
Follow-up cannot maximally increase in muscle tissue because of
Further Outpatient Care proximal arterial stenoses. When the metabolic demands of
1. Patients who have significant peripheral vascular disease the muscle exceed blood flow, claudication symptoms ensue.
but whose illness is not so severe or acute that it At the same time, a longer recovery period is required for
requires inpatient treatment may be discharged with blood flow to return to baseline once exercise is terminated.
appropriate follow-up. However, counsel these patients Similar abnormal alterations occur in distal perfusion
regarding the potential effects of various activities and pressure in affected extremities. In normal extremities, the
medications on the course of their illness. Advise mean blood pressure drop from the heart to the ankles is no
patients to stop smoking and to avoid cold exposures more than a few millimeters of mercury. In fact, as pressure
and medications that can lead to vasoconstriction, travels distally, the measured systolic pressure actually
including medications used for migraines and over-the- increases because of the higher resistance encountered in
counter medications. smaller-diameter vessels.
2. Some recreational drugs (eg, cocaine) may have a At baseline, a healthy person may have a higher measured
deleterious effect on peripheral arterial tone, and beta- ankle pressure than arm pressure. When exercise begins, no
blockers may exacerbate the condition. change in measured blood pressure occurs in the healthy
3. Consultation with providers who will be following the extremity.
patient after ED discharge is advised when making In the atherosclerotic limb, each stenotic segment acts to
decisions regarding the discontinuation of medications reduce the pressure head experienced by distal muscle
used for chronic medical conditions. groups. Correspondingly, at rest, the measured blood
pressure at the ankle is less than that of a healthy person.
Once physical activity starts, the reduction in pressure
produced by the atherosclerotic lesion becomes more
Peripheral Arterial Occlusive Disease
significant and the distal pressure is greatly diminished.
The phenomenon of increased blood flow causing decreased
Background pressure distally to an area of stenosis is a matter of physics.
Claudication, which is defined as reproducible ischemic Poiseuille calculated energy losses across areas of resistance
muscle pain, is one of the most common manifestations of with varying flow rates by using the following equation, in
peripheral vascular disease caused by atherosclerosis. which Q is flow, v is viscosity, L is the length of the stenotic
Claudication occurs during physical activity and is relieved area, r is the radius of the open area within the stenosis, and
after a short rest. Pain develops because of inadequate blood k is constant:
flow. Resistance = pressure = Q8vL/kr4
Pathophysiology Applying this equation, the pressure gradient is directly
Single or multiple arterial stenoses produce impaired proportional to the flow and length of stenosis and inversely
hemodynamics at the tissue level in patients with peripheral proportional to the fourth power of the radius.
arterial occlusive disease (PAOD), shown below. Arterial Therefore, while increasing the rate of flow directly increases
stenoses lead to alterations in the distal pressures available the pressure gradient at any given radius, these effects are
to affected muscle groups and to blood flow. much less marked than those due to changes in the radius of
Peripheral arterial occlusive the stenosis.
disease. This angiogram shows
As the radius is raised to the fourth power, it has the most
a superficial femoral artery
dramatic impact on a pressure gradient across a lesion. This
occlusion on one side (with
reconstitution of the
impact is additive when 2 or more occlusive lesions are
suprageniculate popliteal located sequentially within the same artery.
artery) and superficial femoral Frequency
artery stenosis on the other United States
side. This is the most common Atherosclerosis affects up to 10% of the Western population
area for peripheral vascular older than 65 years. With the elderly population expected to
disease. increase 22% by the year 2040, atherosclerosis is expected to
Under resting conditions, normal blood flow to extremity have a huge financial impact on medicine. When claudication
muscle groups averages 300-400 mm/min. Once exercise is used as an indicator, estimates are that 2% of the
begins, blood flow increases up to 10-fold owing to the population aged 40-60 years and 6% older than 70 years are
increase in cardiac output and compensatory vasodilation at affected.
the tissue level. When exercise ceases, blood flow returns to Mortality/Morbidity
normal within minutes. The most feared consequence is severe limb-threatening
In patients with PAOD, resting blood flow is similar to that of ischemia leading to amputation. However, studies of large
a healthy person. However, during exercise, blood flow
patient groups with claudication reveal that amputation is 5. The perceived significance of claudication is variable.
uncommon. Boyd prospectively followed 1440 patients with Most patients appear to accept a decrease in walking
intermittent claudication for as long as 10 years and reported distance as a normal part of aging. Investigators report
that only 12.2% required amputation. In the Framingham that 50-90% of patients with definite intermittent
study, only 1.6% of patients with claudication reached the claudication do not report this symptom to their
amputation stage after 8.3 years of follow-up. clinician.
1. Limb amputation largely depends on the number and 6. Atherosclerosis is a systemic disease process. Patients
severity of cardiovascular risk factors (ie, smoking, who present with claudication due to PAOD can be
hypertension, diabetes). Continued smoking has been expected to have atherosclerosis elsewhere. A full
identified as the most consistent adverse risk factor assessment of the patient's risk factors for vascular
associated with the progression of peripheral arterial disease should be performed.
occlusive disease (PAOD). Other factors are the severity 7. The risk factors for PAOD are the same as those for
of disease at the time of the initial patient encounter coronary artery disease or cerebrovascular disease and
and, in some studies, the presence of diabetes. include diabetes, hypertension, hyperlipidemia, family
2. As with most patients with vascular disease, survival is history, sedentary lifestyle, and tobacco use.
less than that of age-matched control groups. Coronary 8. Smoking is the greatest of all the cardiovascular risk
artery disease with a subsequent myocardial event is the factors. The mechanism by which smoking causes or
major contributor to outcome. Predicted mortality rates accentuates atherosclerosis is unknown. What is known
for patients with claudication at 5, 10, and 15 years of is that the degree of damage is directly related to the
follow-up are approximately 30%, 50%, and 70%, amount of tobacco used. Counseling patients on the
respectively. importance of smoking cessation is paramount in PAOD
Peripheral arterial occlusive disease (PAOD) has no racial Physical
predilection. Essential to the physical examination of a patient with
Sex claudication is a complete lower extremity evaluation and
1. Intermittent claudication most commonly manifests in pulse examination, including measuring segmental pressures,
men older than 50 years. as depicted in the image below. Atrophy of calf muscles, loss
2. Although younger patients may present with symptoms of extremity hair, and thickened toenails are clues to
consistent with intermittent claudication, other underlying peripheral arterial occlusive disease (PAOD).
etiologies of leg pain and claudication (eg, popliteal Peripheral arterial
entrapment syndrome) must be strongly considered. occlusive disease.
History segmental pressures.
Intermittent claudication typically causes pain that occurs
with physical activity. Determining how much physical
activity is needed before the onset of pain is crucial.
1. Typically, vascular surgeons relate the onset of pain to a
particular walking distance in terms of street blocks (eg,
2-block claudication). This helps to quantify patients with 1. Palpation of pulses should be attempted from the
some standard measure of walking distance before and abdominal aorta to the foot, with auscultation for bruits
after therapy. in the abdominal and pelvic regions. This can be difficult
2. Other important aspects of claudication pain are that the in a patient who is obese, in whom palpable pulses may
pain is reproducible within the same muscle groups and be hidden under a deep subcutaneous layer.
that it ceases with a resting period of 2-5 minutes. 2. Except in the rare case of a congenital absence of a pulse
3. Location of the pain is determined by the anatomical (eg, persistent sciatic artery), the absence of a pulse
location of the arterial lesions. Peripheral arterial signifies arterial obstruction proximal to the area
occlusive disease (PAOD) is most common with the distal palpated. For example, if no femoral artery pulse is
superficial femoral artery (located just above the knee palpated, significant PAOD is present in the aortoiliac
joint), which corresponds to claudication in the calf distribution. The same can be said if no palpable
muscle area (the muscle group just distal to the arterial popliteal artery pulse is present because of existing
disease). superficial femoral artery occlusive disease.
4. When atherosclerosis is distributed throughout the 3. Patients who report intermittent claudication and have
aortoiliac area, thigh and buttock muscle claudication palpable pulses can present a clinical dilemma.
If the history is consistent with typical claudication 3. Neurospinal disease: Pain occurs in the morning and is
symptoms, the clinician can have the patient walk not relieved by short resting periods. Neurospinal pain is
around the office (or perform toe raises) until the frequently relieved by leaning forward against a solid
symptoms are reproduced and then palpate for pulses. surface or by sitting.
The exercise should cause the atherosclerotic lesion to 4. Chronic compartment syndrome: This is rare. It is usually
become significant and should diminish the strength of observed in runners and other athletes with large,
the pulses distal to the lesion. developed calf muscles. Muscles swell during activity,
4. When palpable pulses are not present, further leading to increased compartment pressure and
assessment of the circulation can be made with a decreased venous return. Consistent with claudication
handheld Doppler device. pain, this pain occurs with exercise and is relieved with
An audible Doppler signal assures the clinician that some rest. However, the type of exercise is at a more
blood flow is perfusing the extremity. strenuous level and the recovery period is prolonged.
If no Doppler signals can be heard, a vascular surgeon 5. Popliteal entrapment syndrome: This syndrome is similar
should be immediately consulted. to intermittent claudication but is usually observed in
5. Pressure measurements can be performed to gain active young people. The syndrome is caused by various
objective data on the circulatory status. abnormal anatomical configurations of the insertion of
To obtain an accurate pressure reading, (1) place the the medial gastrocnemius muscle head, which causes
pneumatic cuff around the ankle, (2) position the compression of the popliteal artery. Upon physical
Doppler probe over the dorsalis pedis or posterior tibial examination, tibial pulses may disappear when the knee
artery, and (3) inflate the cuff to a reading above the is at full extension. Pain is aggravated with walking but
systolic pressure and deflate. The systolic tone at the not with running because knee extension is not as severe
ankle vessel is the pressure recorded. with running.
A healthy person has no pressure drop from the heart to 6. Reflex sympathetic dystrophy or minor causalgia: This is
the ankle. In fact, the pressure at the ankle may be 10-20 characteristically described as a burning pain. The
mm Hg higher due to the augmentation of the pressure superficial pain is often distributed along a somatic nerve
wave with travel distally. and is often related to a past trauma in the extremity.
In patients with claudication, the measured pressure is 7. Diabetic neuropathy: Pain is due to a peripheral neuritis.
diminished to some extent, depending on the severity of Differentiation from intermittent claudication can be
PAOD. difficult because of accompanying skin discoloration and
6. A useful tool in assessing a patient with claudication is diminished pulses. An extensive neurologic evaluation is
the ankle-brachial index (ABI), which is calculated as the essential.
ratio of systolic blood pressure at the ankle to the arm. 8. Venous thrombosis: Swelling and leg pain occur with
Determining the ABI provides an assessment of the walking. Pain is relieved by extremity elevation, which
impact that the PAOD is having on the patient. A normal distinguishes this entity from arterial insufficiency.
ABI is 0.9-1.1. However, any patient with an ABI less than Workup
0.9, by definition, has some degree of PAOD. The ABI Laboratory Studies
decreases with worsening PAOD. A laboratory workup is only helpful for identifying
One area of inaccuracy with the ABI is in patients with accompanying silent alterations in renal function and
diabetes who have PAOD. Peripheral vessels in patients elevated lipid profiles.
with diabetes may have extensive medial layer calcinosis, Imaging Studies
rendering the vessel resistant to compression by the 1. Angiography still remains the criterion standard arterial
pneumatic cuff. These patients should be referred to a imaging study used in the diagnosis of PAOD, as depicted
vascular laboratory for further evaluation. in the image below. However, this test is usually
Other Problems to Be Considered reserved for when an intervention (either endovascular
Some disease processes mimic claudication symptoms and or traditional open surgery) is planned.
must be excluded. They include the following: 2. Monaco et al examined the effects of systematic
1. Osteoarthritis: This is associated with arthritic pain that (routine) coronary angiography, as shown below, on
is variable from day to day and may be aggravated by patients undergoing surgical treatment of peripheral
certain weather patterns or movements. Rest does not arterial disease. Patients undergoing vascular surgery
relieve pain. have a high-risk for cardiovascular complications and
2. Venous disease: Described as a dull, aching pain that mortality. The authors found that routine coronary
typically occurs at the end of the day or after prolonged angiography had a positive impact compared with
standing, venous disease is not exacerbated by exercise. selectively determining if coronary angiography was
needed. The routine coronary angiography improved
survival (P=0.01) and no reports of death or 3. Additional medical treatment includes control of the
cardiovascular events (P=0.003) occurred compared with lipid profile, diabetes, and hypertension.
those patients who were selectively chosen to have Surgical Care
coronary angiography prior to vascular surgery. The Patients with limb-threatening ischemia or lifestyle-limiting
authors recommend that multicenter trials confirm this claudication are referred to a vascular surgeon. Only then
finding in a larger population. does evaluation warrant an arteriogram.
3. Magnetic resonance angiography (MRA) is useful for Medication
imaging large and small vessels. Although MRA was Daily aspirin is recommended for overall cardiovascular care.
initially felt to provide inadequate images, this is no While standard dosages range from 81-325 mg/d, no
longer the case. With improved imaging capabilities, consensus has been reached on the most effective dose.
MRA can be used to not only diagnose but to help plan Pentoxifylline (Trental) shows promise. Numerous
the type of indicated intervention. randomized trials have documented modest improvements
4. Computerized tomographic angiography is another in walking distance when compared with placebo treatment
modality used to image arterial disease. Unfortunately, groups. Treatment can take 2-3 months to produce
the study still requires a large amount of contrast media noticeable results.
and requires an upgraded CT scanner to reconstruct The use of clopidogrel bisulfate (Plavix) and enoxaparin
helpful images. sodium (Lovenox) in the treatment of this entity is increasing;
5. Duplex ultrasonography is a method of evaluating the however, further research is needed to establish clinical
status of a patient’s vascular disease. Duplex scanning efficacy.
has the advantage of being noninvasive and requiring no Cilostazol (Pletal) has recently shown increasing promise in
contrast media. Unfortunately, duplex scanning is very the treatment of intermittent claudication. Several
technician dependent. randomized studies have shown benefits in increasing
Treatment walking distances for both the distance before the onset of
Medical Care claudication pain and the distance before exercise-limiting
Treatment of claudication is medical, with surgery reserved symptoms become intolerable (ie, maximal walking distance).
for severe cases. In a randomized, double-blind, placebo-controlled trial,
1. The goal of medical management is to impede the O’Donnell et al assessed the vascular and biochemical effects
progression of peripheral arterial occlusive disease of cilostazol therapy in individuals (n=80) with peripheral
(PAOD). arterial disease. Arterial compliance, transcutaneous
In patients who smoke, the most expedient way to oxygenation, ankle-brachial index, and treadmill walking
impede the progress of PAOD is to stop tobacco use. distance were measured. The cilostazol group had significant
Extensive evidence indicates that smoking cessation reduction in the augmentation index and also showed
improves the prognosis. reduction in transcutaneous oxygenation levels compared
Improved walking distance and ankle pressure have been with the placebo group. Mean percentage change in walking
attributed to smoking cessation. distance improved more in the cilostazol group from baseline
2. Exercise plays a vital role in the treatment of compared with the placebo group. Lipid profiles were also
claudication. improved in the cilostazol group. The results showed that
Patients reduce their daily walking because of cilostazol is an efficacious treatment of peripheral arterial
claudication pain and fear of further damage. This leads disease. In addition to improving patients’ symptoms and
to an increasingly sedentary lifestyle that is even more quality of life, cilostazol also appeared to have beneficial
detrimental. effects on arterial compliance.
Regular walking programs result in substantial In 2009, Momsen et al evaluated the efficacy of drug therapy
improvement in most patients with claudication. in improving walking distance in intermittent
Improvements have ranged from 80-234% in controlled claudication. Their study determined that statins seemed to
studies. be the best in improving maximal walking distance.
A daily walking program of 45-60 minutes is Cholesterol-lowering statin agents are beneficial in the
recommended. The patient is instructed to walk until medical therapy for peripheral arterial disease. In addition to
claudication pain occurs, rest until the pain subsides, and effectively lowering blood cholesterol profiles, recent
repeat the cycle. evidence from the Heart Protection Study showed that
While the exact mechanism for improvement in walking cholesterol-lowering statin agents (simvastatin) reduced the
distance with exercise remains unknown, regular rate of first major vascular events (myocardial infarction,
exercise is thought to condition muscles to work more stroke, or limb revascularization), with the largest benefits
efficiently (more extraction of blood) and increase seen in patients with peripheral vascular disease.
collateral vessel formation.
The benefits were demonstrated regardless of the baseline or other cerebrovascular disease). Competitively inhibits
cholesterol profile. As such, cholesterol-lowering statin HMG-CoA, which catalyzes the rate-limiting step in
agents should be considered for medical treatment in cholesterol synthesis. Patients should be placed on a
patients with peripheral arterial disease. cholesterol-lowering diet; the diet should be continued
Antiplatelet Agents indefinitely.
Decrease overall risk of cardiovascular disease from Adult
myocardial infarction and stroke. Also improve walking 40 mg PO hs if renal insufficiency not severe
distance by enhancing circulation. 5 mg PO hs in patients with severe renal insufficiency; not to
Aspirin (Anacin, Ascriptin, Bayer aspirin) exceed 10 mg/d when coadministered with fibrates (eg,
Inhibits prostaglandin synthesis, which prevents formation of gemfibrozil), niacin (>1 g/d), or cyclosporine; not to exceed
platelet-aggregating thromboxane A2. 20 mg/d when coadministered with verapamil or amiodarone
81-325 mg PO qd Further Outpatient Care
Clopidogrel (Plavix) 1. Patients should be seen every 4-6 months to assess the
Selectively inhibits ADP binding to platelet receptor and effects of medical therapy. Review changes in walking
subsequent ADP-mediated activation of glycoprotein distance, smoking habits, eating habits, and exercise
GPIIb/IIIa complex, thereby inhibiting platelet aggregation. performance.
Indicated for reduction of atherosclerotic events. 2. Control hypertension and diabetes if necessary. A repeat
Adult pulse examination and ABI complete the follow-up
75 mg PO qd evaluation.
3. Patients with worsening symptoms may require
intervention and referral to a vascular surgeon.
Mechanism of effects on symptoms of intermittent
claudication not fully understood. Cilostazol and several of its
1. The most feared consequence is severe limb-threatening
metabolites are PDE III inhibitors, inhibiting
ischemia leading to amputation. However, studies of
phosphodiesterase activity and suppressing cAMP
large patient groups with claudication reveal that
degradation, with a resultant increase in cAMP in platelets
amputation is uncommon.
and blood vessels, leading to inhibition of platelet
Boyd prospectively followed 1440 patients with
aggregation and vasodilation, respectively. Reversibly inhibits
intermittent claudication for as long as 10 years and
platelet aggregation induced by various stimuli, including
reported that only 12.2% required amputation.
thrombin, ADP, collagen, arachidonic acid, epinephrine, and
In the Framingham study, only 1.6% of patients with
claudication reached the amputation stage after 8.3
years of follow-up.
100 mg PO bid at least 30 min before or 2 h after breakfast
and dinner; consider 50 mg bid if coadministered with
1. Whether a patient progresses to limb amputation largely
inhibitors of CYP3A4 (eg, ketoconazole, itraconazole,
depends on the number and severity of cardiovascular
erythromycin, diltiazem) or with inhibitors of CYP2C19 (eg,
risk factors (ie, smoking, hypertension, diabetes).
2. Continued smoking has been identified as the most
consistent adverse risk factor associated with the
Indicated for treatment of patients with intermittent
progression of the disease.
claudication due to atherosclerosis or other obstructive
3. Other factors are the severity of disease at the time of
arteriopathies. Improves blood flow by increasing red blood
the initial patient encounter and, in some studies, the
cell deformability, which decreases viscosity of blood.
presence of diabetes.
4. As with most patients with vascular disease, survival is
400 mg PO tid
less than that of age-matched control groups. Coronary
artery disease, with a subsequent myocardial event, is
These agents are beneficial in lowering blood cholesterol
the major contributor to outcome.
profiles, which may reduce the rate of first major vascular
5. Predicted mortality rates for patients with claudication
at 5, 10, and 15 years of follow-up are approximately
Simvastatin (Zocor) 30%, 50%, and 70%, respectively.
Reduces cardiovascular heart disease mortality and morbidity
(nonfatal myocardial infarction or stroke, revascularization
procedures) in high-risk patients (ie, existing coronary heart
disease, diabetes, peripheral vessel disease, history of stroke