COLLECTIVE REVIEWS
Comprehensive Endovascular Therapy for
Femoropopliteal Arterial Atherosclerotic
Occlusive Disease
Mark G Davies, MD, PhD, FRCSI, FRCS, FACS, David L Waldman, MD, PhD,
Thomas A Pearson, MD, MPH, PhD
year increase in age after the age of 40 years,4-6 with men
developing claudication about twice as commonly as
women. The Framingham Study estimates the incidence
of PAD at 26.6 per 1,000 men and 13.3 per 1,000
women less than 65 years old, but in approximately 20
per 1,000 men and women over 65 years of age.7,8 Mortality in claudicants is up to four times that in the nonclaudicant age-adjusted population.9 Approximately
55% of claudicants will die from heart disease: 10%
from a stroke and 10% from abdominal vascular
pathology.10-14 Less than 20% of claudicants will die
from a nonvascular cause. The strength of association is
so strong that even an asymptomatic patient with a
slightly reduced ankle brachial index (ABI) of 0.9 has a
twofold relative risk of a coronary event.15
Anatomic distribution is important. Patients with isolated aortoiliac disease tend to be younger and have a
lower likelihood of preexisting coronary heart disease.
Those with femoropopliteal disease, infragenicular disease, or multilevel disease tend to have the lowest ABI
and the highest likelihood of coronary heart disease.9,16-21
This review will concentrate on the patient with femoropopliteal disease.
Treatment of the patient with symptomatic femoropopliteal atherosclerotic disease is evolving. The superficial
femoral artery is a common site for infrainguinal atherosclerotic disease, particularly the portion of the superficial femoral artery that lies within the adductor canal of
the thigh. Standard therapy is an exercise program and
risk factor modification. Surgery is reserved for patients
in whom medical treatment fails. Endoluminal intervention coupled with aggressive proactive medical management is replacing these conventional paradigms. Endovascular therapy results in immediate symptom relief.
Initial technical success rates of 90% to 95% have been
achieved for stenotic lesions, and rates of 80% to 95%
for complete occlusions. Longterm patency is often
questioned, but modern series suggest it might be a durable option, particularly if systemic risk factors are aggressively controlled. Anatomic failures do not correlate
with clinical failures. This review outlines the current
management of superficial femoral artery atheroocclusive disease.
Clinical problem
Peripheral arterial disease (PAD) of the lower extremities
remains one of the often unrecognized manifestations of
systemic arteriosclerosis symptomatically affecting between 3% and 7% of the population and up to one in
five patients older than 75 years of age. It has a major
detrimental impact on quality of life1-3 and is an underrecognized marker of multisystem vascular disease. The
risk of disease increases two- to threefold for every 10-
Anatomy
The superficial femoral artery (SFA) is a muscular artery,
which is unique in that it is the longest artery in the
body, and courses through the thigh in the muscular
adductor canal, exiting at a fixed point. The geometry
and elasticity of the SFA are markedly influenced by its
proximity to musculature, its continuous mobility, and
its location between two joints. So it undergoes additional mechanical forces not seen in other arteries. It has
unique elastic wall recoil properties that affect its conformability and resilience.22-24 The flow in the SFA is also
different than in many vessels treated with angioplasty; it
has high resistance characteristics and disturbed flow.25-27
Nonlaminar flow results in increased predisposition to
Supported by grants HL07937, HL04161, and RR00044.
Received January 4, 2005; Revised March 7, 2005; Accepted March 7, 2005.
From the Center for Vascular Disease, Division of Vascular Surgery, Department of Surgery (Davies); the Section of Interventional Radiology, Department of Radiology (Waldman); and the Department of Community and
Preventive Medicine (Pearson); University of Rochester Medical Center,
Rochester, NY.
Correspondence address: Mark G Davies, MD, PhD, University of Rochester
Medical Center, 601 Elmwood Ave, Box 652, Rochester, NY 14642. email:
[email protected]
© 2005 by the American College of Surgeons
Published by Elsevier Inc.
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ISSN 1072-7515/05/$30.00
doi:10.1016/j.jamcollsurg.2005.03.007
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Femoropopliteal Atherosclerotic Disease
Abbreviations and Acronyms
ABI
PAD
PTA
SFA
⫽
⫽
⫽
⫽
ankle brachial index
peripheral artery disease
percutaneous transluminal angioplasty
superficial femoral artery
the development of arteriosclerosis and intimal
hyperplasia.28,29
Pathophysiology
Although arteriosclerosis is a systemic disease affecting all
arteries within the human body, the SFA, because of its
anatomy and physiology, is very susceptible to arteriosclerosis and can demonstrate all aspects of atherosclerotic
plaque development. Arteriosclerosis may be defined as “a
space occupying lesion or plaque of the inner coat of larger
arteries that is focal, has a pattern of occurrence, is composed of an excess of fat, of an increased number of artery
wall and inflammatory cells and their connective tissue
products, and that may show calcification and ulceration,
narrows the arterial lumen, may obstruct blood flow
through the artery and may be associated with a local
thrombus.”30,31
In atherogenesis, the arterial endothelium is considered chronically damaged by serum lipids, turbulent
blood flow, and chronic inflammation. This injury leads
to lipid accumulation and oxidation and the adhesion of
monocytes and platelets with time. The aggregation of
monocytes within the subendothelium constitutes the
first stage of a “fatty streak.” These cells, in concert with
a damaged or “activated” endothelium, synthesize and
release growth factors and cytokines, leading to the migration and proliferation of smooth muscle cells and the
recruitment of additional blood cells, particularly macrophages, filled with oxidized lipids or “foam cells.”32 An
acellular core develops because of the toxic effects of
oxidized lipoproteins. Oxidation of lipoproteins causes
additional tissue injury and increased accumulation of
blood cells and lipids. With time, this process results in
the formation of an atheromatous plaque with a fibrous
cap, an acellular core, and a surrounding myoproliferative and chronic inflammatory response.
Reports by the Committee on Vascular Lesions of the
Council on Arteriosclerosis have established a new classification system for the various types of lesions (I to VI)
described in arteriosclerosis (Fig. 1).30,31 In the older terminology, the fatty streak consists of types I, II, and III
J Am Coll Surg
lesions; the intermediate or fibrofatty lesion, types III,
IV, and Va; and the fibrous plaque or advanced complicated lesion, types Vb, Vc, and VI.30 The SFA demonstrates all these lesions, but by the time the lesion is
symptomatic (ie, manifested by claudication) the fibrous plaque or advanced complicated lesion predominates commonly with associated in situ thrombosis or
occlusion.33
Fibrous plaques may be dynamic lesions that are in a
continuous state of flux or those that are not enlarging
and are considered stable or quiescent. Those that are
expanding or have thinning of the plaque cap represent
unstable or vulnerable lesions.30,31 The findings that the
plaques are dynamic have increased the interest in medical therapies to induce stabilization, regression, or both
in plaque morphology. Plaque growth, whether slow or
abrupt, is usually associated with surface erosion, internal hemorrhage, luminal thrombosis, a combination of
these processes, or gradual vessel occlusion.30,31
The classic plaque represents a raised fibrofatty lesion
with a necrotic core and a fibrous outer coat. Within the
plaques are degenerating blood elements, foam cells,
cholesterol crystals, granulation tissue, smooth muscle
cells, myofibroblasts, capillaries, calcium, iron pigment,
giant cells, mononuclear leukocytes, and necrotic debris.
Adjacent to the internal elastic membrane, which often
exhibits numerous focal disruptions and duplications,
the plaque is frequently characterized by a prominent
deposition of elastin and collagen in an onion skin pattern. The most hazardous component of the atherosclerotic lesion is the plaque margin, where the fibrous cap
of the lesion is thinned and eroded by macrophages and
metalloproteinases they secrete.34 Sudden death from
myocardial infarcts or acutely ischemic limbs are from
these ruptures or fissures in the margins of the fibrous
cap.35
Numerous clinicopathologic investigations have demonstrated that surface weakness is the most common feature of an unstable plaque.30,31,36 Microscopically, the observed sites of injury span a broad morphologic range, from
minimal surface erosions to lacerations that extend deep
within the plaque. The result of these injuries is exposure of
the luminal blood to a thrombogenic surface, setting the
stage for acute thrombosis. Plaque rupture can also lead to
hemorrhage within the atheroma.34 Although the region of
hemorrhage consists primarily of red blood cells, the surfaces along the ruptured tract are often lined by aggregates
of platelets. Plaque hemorrhage can also develop by an en-
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Figure 1. Atherosclerotic plaque. The Committee on Vascular Lesions of the Council on Arteriosclerosis
has established a new classification system for the various types of lesions (I–VI) described in arteriosclerosis (Fig. 1).23,24 In the older terminology, the fatty streak consists of types I, II, and III lesions; the
intermediate or fibrofatty lesion, types III, IV, and Va; and the fibrous plaque or advanced complicated
lesion (types Vb, Vc and VI).24 The superficial femoral artery demonstrates all these lesions, but by the
time the lesion is symptomatic (ie, manifested by claudication), the fibrous plaque or advanced complicated lesion predominates, commonly with associated in situ thrombosis or occlusion. (From: Stary HC,
Chandler AB, Glagov S, et al. A definition of initial fatty streak and intermediate lesions of arteriosclerosis: A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American
Heart Association. Arterioscler Thromb 1994;14:840 – 856, with permission.)
tirely different mechanism. Within the core of a soft atheroma, primary disruption of capillary channels derived from
the vasa vasorum may occur and lead to rapid plaque enlargement. Small hemorrhages are frequently observed in
nonruptured plaques.34 Mechanical stress points for eccentric lesions have been identified at the junction of the
plaque with more normal appearing arterial wall and along
the center of the plaque.34-36 This is likely the basic plaque
morphology that is encountered during percutaneous
transluminal angioplasty (PTA) of the SFA.
Classification of disease
In addition to the atherosclerotic lesion characterizations, there is an anatomic classification of disease based
on angiography or alternative imaging (duplex, computerized tomographic angiography, or magnetic resonance
angiography). The Transatlantic Intersocietal Commission (TASC) has stratified femoropopliteal disease into
four categories: A, B, C, and D.37 These categories are
used for clinical reporting purposes. The definitions are
shown in Table 1, and angiographic examples are given
in Figure 2.
Established and emerging risk factors for
femoropopliteal disease
Claudication is strongly associated with multiple cardiovascular risk factors (Table 2).5,20,38 Of these, smoking
and diabetes mellitus correlate most strongly, and 70%
to 90% of claudicants are either current or ex-smokers.7
Cigarette smoking is associated with a marked increased risk for peripheral arteriosclerosis.5,18,39 Followup of
smokers versus ex-smokers at 7 years shows critical limb
ischemia in 16% of smokers and none in the exsmokers.40 The 10-year incidence of myocardial infarction is five times greater in the smoking group than in
ex-smokers (53% versus 11%, respectively). At 10 years
followup, cardiovascular-related mortality in the smok-
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Femoropopliteal Atherosclerotic Disease
Table 1. Transatlantic Intersocietal Commission Morphologic Stratification of Femoropopliteal Lesions
TASC classification
A
B
C
D
Characteristics
Single stenosis, ⬍ 3 cm, of the superficial
femoral artery or the popliteal artery
Single stenosis, 3 to 10 cm in length, not
involving the distal popliteal artery
Heavily calcified stenoses up to 3 cm in
length
Multiple lesions, each less than 3 cm
(stenoses or occlusions)
Single or multiple lesions in the absence of
continuous tibial runoff to improve inflow
for distal surgical bypass
Single stenosis or occlusion longer than 5 cm
Multiple stenoses or occlusions each 3 to 5
cm, with or without heavy calcification
Complete common femoral artery or
superficial femoral artery occlusions or
complete popliteal and proximal trifurcation
occlusions
TASC, Transatlantic Intersocietal Commission.
ing group is more than 50%, three times that of the
nonsmoking group.
Elevated cholesterol has been shown in the Framingham study to be a weak but important increased risk
factor for claudication.7 Lipid profile abnormalities,
such as elevated serum triglyceride levels and reduced
high density lipoproteins, have been found in the majority of patients in studies of intermittent claudication,41 and there is a strong inverse relationship between
high-density lipoprotein levels and claudication severity.42
Lipoprotein (a) levels have been shown to correlate with
LDL, cholesterol, fibrinogen levels, and PAD severity.43
Studies of lipid-lowering drugs and subsequent vascular
events have focused mainly on coronary disease as a
more frequent end point.
It has been estimated that 50% of diabetic patients
have evidence of PAD.44 Diabetic patients suffer from
both micro- and macrovascular disease manifested often
as ischemia, but more frequently as motor or sensory
neuropathies.45 But a study of 100 consecutive nondiabetic patients attending a vascular clinic showed abnormal glucose tolerance tests in 40%,46 despite the fact that
all 40 patients had normal random or fasting blood glucose levels. There are three clues that might help identify
patients who have a diabetic tendency: first, a distal distribution of PAD in a diabetic pattern; second, a raised
ABI in the presence of symptoms of intermittent claudication; and third, a diabetic picture in the lipid profile.
The relative risk for developing PAD in the presence of
J Am Coll Surg
both smoking and diabetes mellitus is three- to fourfold
higher than with the presence of one factor alone.5,20
Markers of inflammation have been associated
with development of arteriosclerosis and cardiovascular events.47,48 In particular, C-reactive protein is independently associated with PAD, even in patients
with normal lipid levels.49,50 In the Physicians Health
Study, an elevated C-reactive protein level was a risk
factor for development of symptomatic PAD and also
a risk for peripheral revascularization.51 High
C-reactive protein levels are independent predictors
of poor PTA outcomes after revascularization.52
Elevated plasma homocysteine levels appear to be independent risk factors for PAD.53-55 Although B-vitamin
supplements can lower homocysteine levels, the evidence for benefits from supplementation in preventing
cardiovascular events is lacking.56,57 There are suggestions that elevated homocysteine levels are associated
with restenosis after percutaneous transluminal coronary angioplasty.58,59 One study suggests that treatment
with a combination of folate (1 mg), vitamin B12 (400
mcg), and pyridoxine (10 mg) may reduce the rate of
coronary restenosis and the need for revascularization
compared with placebo controls.60
Platelets and their products are known to play a key
role in arteriosclerosis. Platelet aggregability has been
shown to be 30% higher in patients with peripheral
vascular disease even if they are asymptomatic.61,62 Antiplatelet therapy has, not surprisingly, shown considerable reductions in fatal and nonfatal vascular events in
high-risk vascular patients, eg, claudicants.63-65 The risk
reduction for antiplatelet therapy versus placebo in the
claudicant population was 46% for nonfatal stroke,
32% for nonfatal myocardial infarction, and 20% for
death from a vascular cause. Even low risk patients on
antiplatelet therapy have shown small, but considerable,
risk reduction. Claudication progression, as measured
by angiography, has also been shown to be inhibited in
antiplatelet-treated patients.66 A randomized, blinded
trial of clopidogrel versus aspirin in patients at risk of
ischemic events (CAPRIE) had a large subgroup of patients with atherosclerotic vascular disease.67 Clopidogrel was shown to bring about a small, but substantially greater reduction in vascular morbidity and
mortality than aspirin, with a relatively greater effect in
PAD patients than other vascular disease subgroups.
There were no major differences in safety profiles between the two drugs.
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Femoropopliteal Atherosclerotic Disease
279
Figure 2. Transatlantic Intersocietal Commission lesions. The Transatlantic Intersocietal Commission
(TASC) has stratified femoropopliteal disease into four categories: A, B, C, and D. Descriptions of the
categories are shown in Table 1. The panel of angiograms depicts the lesions. TASC A/B lesions are
shown in the left panel, TASC C lesions are in the middle panel, and TASC D lesions are in the right panel.
Hemostatic abnormalities are found frequently in PAD
and could contribute to pathogenesis or be markers of disease progression.68-70 The presence of the lupus anticoagulant and elevated markers of platelet activation (beta thromboglobulin levels) has been associated with peripheral
arteriosclerosis.71,72 Hemostatic abnormalities are present in
diabetic patients, with greater evidence of thrombin generation than in nondiabetic patients.73 Clinical studies on
patients undergoing peripheral bypass surgery have demonstrated the presence of a definite subset of patients with
abnormal coagulation profiles.74 After adjustment for age
and gender, von Willebrand factor, fibrin, D-dimer, and
urinary fibrinopeptide A are elevated in claudicants, and
the risk for claudication is substantially raised with unit
changes in each factor.75,76
Male patients with PAD have been demonstrated to
have normal prothrombin and partial thromboplastin
times.77 In addition, there appear to be no notable differences in alpha 2 macroglobulin, C1 inactivator, and
antithrombin III. Enhanced levels of fibrinogen, ␣-1antitrypsin, thrombin/antithrombin III complex, ␣-2 plasmin inhibitor/plasmin complex, and thrombomodulin
were documented in claudicants.77 Compared with healthy
control subjects, patients with PAD showed higher t-PA
antigen, PAI-1 antigen, and D-dimer levels both at rest and
after exercise. Thrombin formation is enhanced in these
patients with PAD after submaximal treadmill exercise.
Cumulatively, these data suggest that patients with PAD
suffering from claudication are relatively hypercoagulable.
The significance of such findings is unknown,77,78 and to
date, no hemostatic factor or combination has been associated with failure or restenosis of PTA in PAD.79
Management of patients with PAD
General
The management of patients with intermittent claudication has traditionally focused on relief of symptoms.
But the realization that claudication is part of a generalized vascular disease with high mortality has led to a
recent and substantial broadening of treatment strategies. The main goals of medical care should be reduction
in cardiovascular risk on a systemic basis accompanied
by alleviation of the symptoms of intermittent claudication.80,81 Current recommendations are that all PAD pa-
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Table 2. Optimal Medical Management in the Patient with Peripheral Artery Disease: Goals, Interventions, and Recommendations
Risk intervention and goals
Smoking
Goal: Complete cessation. No exposure to
environmental tobacco smoke.
Blood pressure control
Goal: ⬍ 140/90 mmHg: ⬍ 130/85 mmHg if renal
insufficiency or heart failure is present; or ⬍ 130/80
mmHg if diabetes is present.
Dietary intake
Goal: An overall healthy eating pattern.
Lipid management
Primary goal: LDL-C ⬍ 70 mg/dL.
Secondary goal: If triglycerides ⬎ 200 mg/dL,
non HDL ⬍ 30 mg/dL.
Other targets: triglycerides ⬍ 150 mg/dL, HDL ⬎ 40
mg/dL in men, ⬎ 50 mg/dL in women.
Physical activity
Goal: At least 30 min of moderate-intensity physical
activity on most (and preferably all) days of the
week.
Weight management
Goal: Achieve and maintain desirable weight body
mass index 18.5–24.9 kg/m2. When body mass
index is ⱖ 25 kg/m2, waist circumference at iliac
crest level ⱕ 40 inches in men, ⱕ 35 inches in
women.
Diabetes management
Goals: Normal fasting plasma glucose (⬍ 110 mg/dL)
and near normal HbA1c (⬍ 7%).
Aspirin
Goal: All patients on an antiplatelet agent.
Recommendations
Ask about tobacco use status at every visit. In a clear, strong, and personalized
manner, advise every tobacco user to quit. Assess the tobacco user’s
willingness to quit. Assist by counseling and developing a plan for quitting.
Arrange followup, referral to special programs, or pharmacotherapy. Urge
avoidance of exposure to secondhand smoke at work or home.
Promote healthy lifestyle modification. Advocate weight reduction; reduction
of sodium intake; consumption of fruits, vegetables, and low-fat diary
products; moderation of alcohol intake; and physical activity in persons with
blood pressure of ⱖ 130 mmHg systolic or 80 mmHg diastolic. For persons
with renal insufficiency or heart failure, initiate drug therapy if blood
pressure is ⱖ 140/90 mmHg if 6 to 12 mo of lifestyle modification is not
effective, depending on the number of risk factors present. Add blood
pressure medications, individualized to other patient requirements and
characteristics (eg, age, race, need for drugs with specific benefits).
Advocate consumption of a variety of fruits, vegetables, grains, low-fat or
nonfat dairy products, fish, legumes, poultry, and lean meats. Match energy
intake with energy needs and make appropriate changes to achieve weight
loss when indicated. Modify food choices to reduce saturated fats (⬍ 10% of
calories), cholesterol (⬍ 300 mg/d), and trans-fatty acids by substituting
grains and unsaturated fatty acids from fish, vegetables, legumes, and nuts.
Limit salt intake to ⬍ 5 g/d. Limit alcohol intake (ⱕ 2 drinks/d in men, ⱕ 1
drink/d in women) among those who drink.
Initiate lifestyle changes consisting of dietary modification, including use of
plant sterols (⬍ 2 g/d) and increased fiber. Rule out secondary causes. Start
drugs and advance dose to bring LDL-C to goal. Usually statin or
combination of drugs with a statin. If non HDL-C elevated, consider lifestyle
changes, or niacin or fibrates. If HDL-C low, consider niacin or fibrates.
If cardiovascular, respiratory, metabolic, orthopaedic, or neurologic disorders
are suspected, or if patient is middle-aged or older and is sedentary, consult
physician before initiating vigorous exercise program. Moderate-intensity
activities (40% to 60% of maximum capacity) are equivalent to a brisk walk
(15–20 min per mile). Additional benefits are gained from vigorous-intensity
activity (⬎ 60% of maximum capacity) for 20–40 min on 3–5 d/wk.
Recommend resistance training with 8–10 different exercises, 1–2 sets per
exercise, and 10–15 repetitions at moderate intensity ⱖ 2 d/wk. Flexibility
training and an increase in daily lifestyle activities should complement this
regimen.
Initiate weight-management program through caloric restriction and
increased caloric expenditure as appropriate. For overweight or obese persons,
reduce body weight by 10% in first year of therapy.
Initiate appropriate hypoglycemic therapy to achieve near-normal fasting
plasma glucose or as indicated by near-normal HbA1c. First step is diet and
exercise. Second-step therapy is usually oral hypoglycemic drugs;
sulfonylureas and/or metformin with ancillary use of acarbose and
thiazolidinediones. Third-step therapy is insulin. Treat other risk factors
more aggressively (eg, change blood pressure goal to ⬍ 130/80 mmHg and
LDL-C goal to ⬍ 100 mg/dL).
Patients should be on 81 mg of aspirin/d unless contraindicated. Clopedigrel
may also be considered at 75 mg/d.
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tients should receive antiplatelet therapy, stop smoking,
exercise, and be screened and treated for hyperlipidemia,
hypertension, diabetes, and hypercoaguability in accordance with national guidelines and community standards
(Table 2).
Smoking
Smoking cessation is a priority in the addicted claudicant. More than 75% of claudicants who already smoke
will have tried and failed to quit smoking. Up to 25% of
patients will try to follow clinical advice to stop smoking, but more than 75% of these will recommence in less
than 3 months.82 With medical advice alone, only 5% of
claudicants will have longterm success in quitting.83 Nicotine replacement therapy such as chewing gum, transdermal patches, nasal sprays, and inhalers are effective in
helping patients stop. A metaanalysis of trials shows a
1.5- to 2-fold increase in cessation rate, with nasal spray
and inhaled nicotine showing most success.84 Combining nicotine replacement therapy with treatments such
as an inhaler with a patch increases the success rate to
nearly 20% at 1 year.85
Amfebutamone or bupropion (Zyban, GlaxoSmithKline)
is an atypical antidepressant that has recently been licensed as an aid to smoking cessation. It reduces the
hypertensive, cardiac, and other side effects of nicotine
withdrawal. Trials suggest up to 30% 1-year cessation
rates, with a dose-related response.86 The goals for the
care of these patients should be accessible specialist
smokers’ clinics, where counseling, education, and support by specialists in tobacco cessation can be combined
with appropriate pharmacologic treatment.87
Exercise
Exercise therapy produces considerable improvements
in the symptoms of claudicants.88-90 Physical improvements gained from an exercise regimen are both multifactorial and systemic.91 These include compensatory
adaptations and redistribution of peripheral blood flow,
changes in oxidative capacity of skeletal muscle with
greater use of oxygen, changes in blood composition,
inhibition of additional atherosclerotic disease, and improvements in the cardiorespiratory system.92 A study of
34 claudicants after a supervised exercise regimen over 6
months found a doubling of pain-free walking distance.1
There was also a mean drop in systolic blood pressure of
5.7% and a fall in mean cholesterol levels of 5.2%. Concerns about claudicants developing an inflammatorytype response during walking, which may be harmful,
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Femoropopliteal Atherosclerotic Disease
281
appear unfounded. Regular exercise training produces a
reduction in the inflammatory markers associated with
endothelial damage.93 So evidence suggests that patients
following an exercise regimen improve both claudication distance and cardiovascular risk profile.
Three separate metaanalyses of exercise regimen trials
identified similar components in the most successful
programs.94-98 Common factors were exercise duration
of greater than 30 minutes per session, frequency of at
least three sessions per week, walking as the mode of
exercise, exercising to near maximal pain tolerance, and
a program lasting 6 months or longer. In claudicants,
there appears to be equal benefit if the patient undergoes
upper limb exercise or lower limb exercise. Pain-free and
maximum walking distance improvements were seen
with both forms of exercise.97 This is likely a function of
total body conditioning because all exercise should give
improvements in cardiovascular function; walking will
give additional adaptive benefits in the muscle groups
affected by claudication. The role of supervised exercise
classes versus best exercise advice given in clinic has still
to be determined on a large trial basis.
Lipid lowering therapy
Patients with symptomatic peripheral vascular disease
should be considered within the high risk groups as defined by the Adult Treatment Panel III (ATP-III) of the
National Cholesterol Education Program.99,100 The goal
of lipid lowering therapy should be set at a LDLcholesterol level of ⱕ 70 mg/dL. Hypertriglyceridemia
(⬎ 200 mg/dL) is also prevalent in the peripheral vascular disease population and should be treated.101 The
Adult Treatment Panel III identifies the sum of LDL
and very-low density lipoprotein (VLDL), termed nonHDL cholesterol, (⫽ [cholesterol]-[HDL]) as a secondary target for therapy in patients with high triglycerides
(ⱖ 200 mg/dL). The goal for these patients is non-HDL
cholesterol of ⱕ 30 mg/dL.99,100 Despite the known lipid
profile abnormalities in claudicants and the proved and
theoretic advantages of lipid-lowering drugs,46,99,102 few
studies have targeted relief of claudication symptoms as
an end point.103,104 A recent review by the Cochrane
peripheral vascular disease group identified only seven
suitable randomized trials of lipid lowering therapy (not
statins) in patients with lower limb arteriosclerosis.104,105
Lipid lowering therapy results in a marked but unimportant reduction in mortality and no change in nonfatal
events. Two of these trials did demonstrate a substantial
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reduction in disease progression as quantified by
angiography.105
The role of lipid lowering regimens in the treatment
of claudication has recently been readdressed. The Scandinavian Simvastatin Survival Study (4S) had demonstrated that subjects randomized to simvastatin had a
38% reduction in new or worsening claudication compared with subjects randomized to placebo,106 and several recent studies demonstrated improved walking ability in patients treated with statin compared with patients
without a statin, independent of cholesterol levels and
other potential confounders.107-109
Pharmacologic therapy
Multiple drugs and regimens have been tested in claudication; five oral drugs have been licensed for the treatment of claudication. Two of these, inositol nicotinate,
and cinnarizine, have not been established as effective
when compared with placebo. Pentoxifylline (oxypentifylline) has been shown, in a metaanalysis, to improve
walking distance by 29 meters over placebo (the improvement was approximately 50% compared with
baseline in the placebo group; pentoxifylline provided
an additional 30% improvement). Naftidrofuryl has
shown an increase in walking distance of up to 30%
when compared with a placebo at 6 months. Cilostazol,
a phosphodiesterase inhibitor, has shown a 40% increase
in walking distance at 3 months and has become the
drug of choice in the pharmacologic management of
claudication.98,110,111 Oral drug therapy should always be
combined with exercise and risk factor modification.
Gene therapy
Molecular therapies to induce angiogenesis are appealing in
the claudicant population because the ischemia is subacute,
time for angiogenesis to occur is available, and collateral
development is associated with improved symptoms and
increased walking distance. Molecular therapies that result
in increased levels of vascular endothelial growth factor,
fibroblast growth factor, and hepatocyte growth factor have
been used in claudication populations.112 The RAVE Trial
(Regional Angiogenesis with Vascular Endothelial Growth
Factor in Peripheral Arterial Disease) concluded that a single unilateral IM administration of adenoviral vascular endothelial growth factor121 was not associated with improved treadmill exercise performance or quality of life over
placebo.113 The most recent Therapeutic Angiogenesis with
Recombinant Fibroblast Growth Factor-2 for Intermittent
Claudication (TRAFFIC) study has shown that intraarte-
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rial fibroblast growth factor will result in a considerable
increase in walking time at 90 days.114 These therapies are
not readily available and have not been compared with
standard aggressive medical and endoluminal management
of claudication.
Endoluminal procedures
Because of the introduction of PTA in 1964 by Dotter
and Judkins115 and its refinements by Gruntzig,116 PTA
has grown into a viable alternative to surgical intervention in most arterial beds. The diseased SFA may be
approached with a repertoire of techniques. The conventional approach is to access the SFA in an antegrade
manner and negotiate a guide wire through the target
lesion before performing PTA (Fig. 3A). A similar approach can be achieved in short segment occlusions (Fig.
3B). An antegrade transfemoral approach has initial
technical success rates of 90% to 95% for stenotic lesions and 80% to 95% for complete occlusions. Use of
the retrograde transpopliteal approach can increase the
original technical success rate by an additional 6%.117
But longer occlusions require additional techniques.
Percutaneous intentional extraluminal recanalization,118
or subintimal angioplasty or Bolia angioplasty, is a technique used to recannulize chronic occlusions.119 It intentionally achieves a dissection plane in the vessel wall to
circumvent a total occlusion. Gaining luminal access
into the distal target vessel remains the Achilles’ heel of
this approach. Recently, the use of intravascular ultrasound to identify and guide a needle from the false dissected lumen into the true lumen has been shown to be
effective. Percutaneous intentional extraluminal recanalization through the retrograde popliteal approach can
be achieved in up to 80% of patients (Fig. 3C).120
Pathology of angioplasty and stenting
Angioplasty is a controlled injury to the vessel wall. Although there is no apparent loss of cells from the media
of the vessel wall after balloon injury, studies show that
approximately 20% of total wall DNA is lost. Some of
this loss is of endothelial origin, but a considerable
amount reflects injury to the underlying medial smooth
muscle cells.121 In the immediate aftermath of angioplasty, programmed cell death, or apoptosis, can be identified at 1 to 2 hours and disappears by 4 hours.122 No
apoptosis can be identified in the wall after injury at 3
days but by day 7, 50% of the cells again show signs of
apoptosis and by day 14, the number of apoptotic cells is
again markedly decreased.
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283
Smooth muscle cell proliferation within the media,
which is normally less than 1%, increases to more than
20% within 48 hours after angioplasty.121,123,124 The
fraction of cells proliferating reaches a maximum between 3 and 7 days and occurs as a synchronous wave of
entry into the S phase of the medial smooth muscle.125,126
This first phase of smooth muscle cell proliferation appears to be driven by basic fibroblast growth factor released from dead and damaged cells in the vessel wall
after balloon injury, and approximately 80% to 90% of
this response can be prevented by inhibition with basic
fibroblast growth factor antibodies. Four weeks after injury, the medial proliferative response returns to baseline
levels. Intracoronary radiation after angioplasty inhibits
this first wave of cell proliferation and prevents adventitial proliferation.127 By day 8 after the injury, smooth
muscle cells are observed on the luminal side of the
internal elastic lamina and appear to have migrated to
the luminal surface through fenestrations in the internal
elastic lamina. The number of smooth muscle cells in the
intima increases to a maximum at 2 weeks after injury,
and about 30% of medial smooth muscle cells may migrate from the media to the intima.
This migration of cells requires degradation of the
cage of matrix surrounding each cell by proteases and
the synthesis of new matrix molecules. Migration of
the smooth muscle cells from the media to the intima
across the internal elastic lamina is mediated in part
by platelet derived growth factor.128
Smooth muscle cell migration is unaffected by irradiation and antimitotic drugs.129-132 Once within the intima, approximately 50% of the smooth muscle cells
Figure 3. Therapeutic results. (A) This panel of angiograms of the
superficial femoral artery shows a Transatlantic Intersocietal Commis-
sion B lesion (left [L]; arrows). This lesion was successfully treated
with balloon angioplasty. Luminal diameter is improved with evidence of a nonflow limiting dissection in the wall (right; arrows). The
patient experienced symptomatic relief. (B) This panel of angiograms of the superficial femoral artery shows a nonocclusive Transatlantic Intersocietal Commission C lesion (left [L]; arrow). This
lesion was successfully treated with balloon angioplasty (right; arrow) and symptom relief has been maintained for 2 years. (C) This
panel of angiograms of the superficial femoral artery shows a long
Transatlantic Intersocietal Commission D lesion (left [L]) approached from the popliteal approach. The vessel was successfully
recanulized and primarily stented along its entire length (middle
[M]). Flow was restored with no defects (right). The patient experienced symptomatic relief, which lasted for 6 months. In-stent restenosis was encountered and successfully treated with balloon angioplasty. Symptom relief has been maintained for an additional
12 months. CFA, common femoral artery; SFA, superficial femoral
artery; PFA, profunda femoris artery.
284
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Femoropopliteal Atherosclerotic Disease
proliferate (a second phase of mitosis). In the intima, a
second phase of cellular proliferation is first noted at day
7 and reaches a maximum at 14 days before returning to
baseline by 28 days.126 But it may continue for up to
12 weeks in areas where reendothelialization takes
longer to complete. This second phase of smooth muscle
cell replication in the intima appears to be mediated by
autocrine and paracrine factors and remains poorly understood. It also appears that the thickness of the intimal
hyperplasia peaks within 1 month, and its rapid development is from both cellular elements and the production of proteoglycans.
Associated with the changes in the intima and media,
there are substantial changes in the adventitia, as evidenced by increased cell proliferation and growth factor
synthesis in the adventitia relative to the media after
angioplasty. In the adventitia, there is a marked infiltrate
of cells termed “myofibroblasts” by day 2, which by day
14, can represent up to 50% of cells within the
intima.133,134 The presence of myofibroblasts is common
in wound healing and leads to contraction of the wound.
A similar phenomenon may occur in the healing vessel.
Injured vessels can undergo chronic elastic recoil or negative remodeling, resulting in loss of luminal dimensions
without an additional increase in neointimal area. Retrieved atherectomy material from primary and restenotic lesions has shown that the proportion of cells,
which can be demonstrated to be proliferating in the
restenotic lesion, is low,135 but that migratory activity
and collagen synthesis of human smooth muscle cells
from the restenotic lesions are greatly elevated, strongly
supporting the concept that remodeling is important in
the final determination of luminal diameter.136,137
The degree of intimal hyperplasia that develops in a vessel is dependent on the length and depth of the injury.138
Minimal intimal proliferation occurs when the media is
uninjured, but intimal hyperplasia increases in proportion to the depth of the medial injury, indicating that
the proliferative response reflects the direct injury to the
smooth muscle cells.139,140 In addition, distention of
smooth muscle cells without severe endothelial cell injury has been shown to result in smooth muscle cell
proliferation. The length of the injury influences the
duration of the reendothelialization process. Reendothelialization occurs from the margins of the denuded area
and possibly from the endothelial cells of the vasa vasorum. The longer there is an incomplete endothelial cell
covering, the greater time the smooth muscle cells are
J Am Coll Surg
without the modulating influence of the endothelial
cells, and the longer the replication phases of the smooth
muscle cells will be.121,123 After deep vessel wall injury,
luminal narrowing may be less dependent on intimal
hyperplasia formation and more dependent on vessel
wall remodeling.141 Medial damage is accompanied by a
massive adventitial cell proliferation,142 which, in time,
provides cells capable of contraction and negative
remodeling.
Intravascular stents
The biology of in-stent restenosis is different than that
seen after balloon angioplasty.143 A stent is generally used
if the result of balloon angioplasty is technically unsatisfactory or if there is arterial occlusion, immediate elastic recoil, flow-limiting dissection, or restenosis. The response of a vessel to a stent is dependent on the stent
design, length, composition, delivery system, and deployment technique.144 In-stent restenosis is classified
on the basis of length of restenosis in relation to stented
length. Four categories of in-stent restenosis have been
defined: focal (ⱕ 10 mm length), diffuse (⬎ 10 mm
length) proliferative (⬎ 10 mm length and extending
outside the stent), and occlusion.145 After balloon angioplasty, there is thrombus formation, intimal hyperplasia
development, elastic recoil, and negative remodeling. In
contrast, after stent placement, elastic recoil and negative remodeling are eliminated146 and thrombus formation followed by intimal hyperplasia development are
the main contributors to in-stent restenosis.147
Patients with diabetes and earlier restenosis have a
higher rate of in-stent restenosis,148 and there is a correlation with prolonged in-stent thrombus and hyperglycemia.149 Stent placement in a vessel results in generalized injury to the length of the vessel exposed and in
more focal injures at the areas of strut placement. Intravascular ultrasound has demonstrated that stents do not
always completely oppose the vessel wall along its entire
length, resulting in uneven injury along its length.146
After stent placement, the surface of the metal implanted into the vessel is covered by a strongly adherent
monolayer of protein within 5 seconds. After 1 minute
the surface is covered by fine layers of proteins, predominantly fibrinogen.150 The holes between the stent wires
are filled with thrombus and the adherence of platelets
and leukocytes is enhanced by disturbance of electrostatic equilibrium.151,152
The basic mechanisms of smooth muscle cell prolif-
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285
Table 3. Categories of Clinical Success after a
Vascular Procedure
Category
Result
Anatomic
Primary patency
Assisted primary patency
Secondary patency
Ankle brachial index rise of 0.15
Symptoms improve by at least one category
(SVS grade)
Hemodynamic
Clinical
SVS, Society of Vascular Surgery.
eration and migration after stent placement are the same
as those after balloon injury.153 The intimal hyperplasic
process in a stent is more prolonged and robust than in a
balloon-injured artery and is proportional to the depth
of injury the recipient vessel sustains154 and the inflammatory response induced.155 It can often be much more
pronounced at the ends than in the body of the stent. In
addition, the adventitial response is prolonged, with adventitial giant cell body formation noted. Stents prevent
chronic elastic recoil and cause progressive atrophy of
the media.156
Outcomes
National reporting standards for vascular procedures define three categories of clinical success: anatomic, hemodynamic, and clinical (Table 3). A composite analysis of
all published trials of PTA with or without stenting in
the femoropopliteal arteries showed patencies of 71%,
59%, and 53% at 1, 3, and 5 years, respectively (Fig. 4).
Technical success was 90%, with a complication rate of
10% (Table 4). Multiple factors can adversely affect patency; these include presenting symptoms (claudication
versus critical ischemia), type of lesion (stenosis versus
occlusion), length of lesion (⬍ 10 cm and ⬎ 10 cm), and
distal runoff 157-160 (Table 5). The presence of diabetes
also influences longterm patency.161
Jorgenson and colleagues162 suggested that restricting
the area of dilation and using the smallest necessary balloon to reduce vessel wall injury would be beneficial, but
the clinical benefit of this approach has not been shown.
Prolonged dilation, although a safe procedure, does not
result in superior longterm patency rates.163 Two studies
suggested that no factor contributed to longterm failure.164,165 Patients with diabetes have been shown to have
worse outcomes than patients without diabetes.158,161,166,167 Patients treated for critical ischemia have
lower patency rates than patients treated for claudication.158,159,167,168 Stenoses are associated with better patency
Figure 4. A composite analysis of all published trials of percutaneous transluminal angioplasty with or without stenting in the femoropopliteal arteries showing patencies for stenotic and occlusive
lesions out to 5 years. Values are the median cumulative primary
patency.
than occlusions, but if technical failures are excluded, patency rates are similar between both lesions.158-160,169-171
Concentric lesions have also been found to be more
favorable than eccentric lesions,158,172 and focal stenoses
fare better than long segment lesions.158,166,167,172,173 In
most cases, poor runoff correlates with worse outcomes.160,167,172 There is a high incidence of thrombosis
within hours of angioplasty of total occlusions, which is
independent of the length of the lesion.174 Predictors of
immediate PTA failure are diastolic hypertension and
the percent stenosis.164 Male gender and presence of a
lower atherosclerotic burden are associated with a lower
complications rate.117
London and associates175 demonstrated that continued smoking, poor runoff, and length of occlusion were
important risk factors for occlusion after percutaneous
intentional extraluminal recanalization. In a prospective
registry, Laxdal and coworkers176 showed that subintimal
angioplasty has a poor patency at 18 months, and the
Table 4. Reported and Maximal Limitations to Accept Technical Complications with Percutaneous Transluminal Angioplasty (Society of Cardiovascular and Interventional Radiology 1990)
Technical complication
Acute operation
Severe hematoma
Acute occlusion
Distal embolization
Perforation
Literature
(%)
Maximum to
accept (%)
⬍1
⬍2
⬍0.5
⬍0.1
⬍0.1
⬍3
⬍4
⬍3
⬍0.5
⬍0.5
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Femoropopliteal Atherosclerotic Disease
Table 5. Factors Influencing the Patency of Superficial Femoral Artery Interventions
Factors
Positive
⬍ 2-cm lesions
Noncalcified lesions
⬎ 3.5-mm diameter vessel
No use of thrombolytics
Nonsmokers
Low C-reactive protein
Negative
Occlusions
Segments stented ⬎ 10 cm
⬎ 30% residual stenosis
Poor tibial runoff
Serum creatinine ⬎ 1.3 mg/dL
Noncontributory
Age
Race
Experience of operator
major factors contributing to occlusion are the presence
of diabetes and critical ischemia.
If intravascular ultrasonography is used immediately
after PTA, the extent of dissection, free lumen area, and
diameter are predictive factors of patency.177 Factors of
intravascular ultrasound that favor improved patency are
the absence of calcification, dissection or plaque rupture, and a residual stenosis of less than 30%.178 Intravascular ultrasound predictor of failure at 1 and 6
months is initial residual stenosis after PTA.179 Similarly,
pronounced residual stenosis (⬎ 30%) on duplex ultrasound 1 day after PTA correlates with failure within 1
year; unfortunately, the converse is not true; a normal
duplex at ⫹ 1 day cannot predict failure within 1 year.180
Plaque area increase and vascular remodeling contribute to lumen area change after PTA of the femoropopliteal artery on intravascular ultrasound study.181 Capek
and coauthors158 and Hunink and colleagues159 showed
that repeat PTA has similar patency as does primary
PTA; in contrast, several reports showed that repeat SFA
angioplasty has a low patency (⬍ 20% at 3 years) and
suggested that bypass may be more beneficial.182-185 Failure of PTA is not associated with worsening of the patient’s clinical condition, and 19% will be recannulized
at a second sitting.186,187
Hemodynamic success is defined as an increase in ABI
of 0.15. Immediate and longterm hemodynamic success
(ABI ⬎ 0.15) after PTA is directly related to tibial run-
J Am Coll Surg
off.188 Most studies have shown an appropriate increase
in ABI after PTA. The duration of the increase is unknown and may or may not correlate with symptom
improvement. When operation is compared with PTA
for lesions appropriate for PTA, there are no notable
differences between bypass operations and PTA.182,189
Studies of patients after operation (ie, iliofemoral or
femoropopliteal bypass) have shown that at 6 weeks,
there is an improvement in resting ABI and improved
treadmill testing.37 Optimal results appear to be restricted to patients younger than 70 years, who are not
diabetic, and in whom a normal ankle pressure is anticipated based on the lesion corrected and the anatomic
distribution of PAD. But up to 20% of patients will be
dissatisfied with their surgical outcomes, even though
50% of this dissatisfied subgroup will have a normal
postoperative ABI.190 Similar data are not yet available
for PTA of the SFA.
Although anatomic patency and hemodynamic success are important, the primary reasons to perform an
intervention are symptom relief and longterm clinical
success. Karch and colleagues191 demonstrated that 40%
of patients remain symptom free 4 years after SFA angioplasty. Clinical failures are only partially related to
anatomic patency of the treated area, and other factors,
such as progression of disease in the inflow vessels in the
treated vessel and in the outflow tract, are also implicated. Half of these lesions are amenable to additional
percutaneous intervention. These findings that clinical
success appears to be higher than anatomic success has
been reported by others.192,193 Predictors of clinical failure in the immediate period were age, SFA occlusion,
and angioplasty rating (ie, residual stenosis, presence of
dissection, occlusion); predictors in the early period (⬍
12 months) were age, SFA occlusion, degree of arteriosclerosis, and angioplasty rating; in the late period (⬍
12 months), only angioplasty rating was important.194
Pharmacotherapy after PTA
The role of pharmacotherapy after PTA in the SFA has
been driven by data derived from the coronary artery
interventional literature. Heiss and associates,195 showed
a major benefit of aspirin compared with placebo after
PTA, but antiplatelet drugs have not shown a consistent
benefit in preventing restenosis.196,197 Low dose aspirin
appears as effective as high dose aspirin in the prevention
of restenosis.198 The coronary literature supports the use
of the combination of aspirin and clopidogrel after en-
Vol. 201, No. 2, August 2005
doluminal intervention. No data are readily available for
periphery interventions, but most centers add clopidogrel before and after intervention. The required duration of this additional therapy has not been tested.
Whether statins are beneficial after peripheral angioplasty is unanswered by level 1 evidence, but given the
fact that patients with SFA disease should have their
cardiovascular risk factors managed aggressively, it is
likely to be a moot point.
Adjuvant stenting
Four randomized studies comparing PTA alone versus
PTA plus stent placement in the SFA all failed to
demonstrate a benefit to stenting in terms of longterm
patency and symptom relief.199-202 There is little evidence to support the superiority of endovascular
stents over PTA alone in the femoropopliteal arteries.
Their use should be confined at present to flow limiting dissections or inadequate results from balloon
angioplasty alone.200,203,204 Cheng and coauthors205
suggested that major factors that impede stent patency were occlusions, stented segment length
⬎ 10 cm, procedure in claudicants, and the use
of Memotherm (Bard) stents. Liermann and colleagues206 reported a primary patency rate of 82%
after 18 months and noted a lower patency rate for
stents placed in the distal portion of the SFA compared with the proximal portion. Strecker and associates170 reported a 2-year patency rate of 73% for stent
placement for stenosis and 32% in occlusions.
Use of wall stents for short lesions and stenoses reveals
a 1- to 2-year primary patency of 67%; for occlusions
this dropped to 49%.171 One report suggested a high rate
of early thrombosis and restenosis rate of 77% when
wall stents are placed in the SFA.207 There are no peer
reviewed data in press on the longterm performance of
nitinol stents in the SFA. One report noted that the
12-month restenosis of nitinol stents was 46%, which
was not influenced by the cumulative length or the number of stents placed, but was worsened in the presence of
diabetes.208
In a bid to counteract in-stent restenosis, covered
stents have been proposed.209 There appears to be an
initial gain in patency over the first 6 months.210 Although this strategy did prevent in-stent restenosis, it
did not prevent development of intimal hyperplasia at
the ends of the device.211 Reocclusion rates of 32% to
43% in the first 12 to 18 months after implantation have
Davies et al
Femoropopliteal Atherosclerotic Disease
287
been reported.211-214 Reconstructive operations in patients
presenting with infrainguinal stent occlusion or restenosis
appear to be associated with higher morbidity and major
limb amputation rates.215
Drug eluting stents
Although several drug eluting stents have been used in
the coronary circulation, only one, the sirolimus eluting
SMART stent (Cordis Endovascular), has data available
for the periphery. The results of the SIROCCO studies
showed that despite excellent 6-month patency observed
in the bare nitinol stent group, comparative analysis revealed a reduction in neointimal hyperplasia in the
sirolimus eluting stents.216,217 It did not appear that these
stents had a major clinical effect.
Atherectomy
Debulking of lesions may enhance patency. Atherectomy devices and endovascular endarterectomy have
been used to achieve these aims. Directional atherectomy appears to have a 75% patency at 24 months, but
there is a high restenosis rate.218 Endovascular SFA endarterectomy appears to have a 65% technical success rate
and a cumulative patency of 59% in patients in whom
technical success can be achieved.219 Directional atherectomy has a patency of 57% at 2 years in patients with
diabetes, complete luminal occlusion, or critical ischemia having lower patencies.220 Studies have suggested
that debulking segments before adjunctive balloon angioplasty may offer advantages in reducing acute complications and improving longterm patency.221,222 In addition, treatment of in-stent restenosis may be helped by
debulking before dilation.223
Several mechanical atherectomy devices have been
used in the treatment of peripheral vascular disease. The
Simpson Atherocath is commonly used to treat focal
eccentric lesions in larger vessels and bypass graft anastomoses. It is limited by its high profile and side-cutting
design. The Silverhawk catheter (Foxhollow Inc), which
is derived from the Simpson catheter, has reduced these
obstacles to catheter placement and use. Case series suggest that it has short-term benefits.224-226 Rotational
atherectomy (Rotablator, Boston Scientific) uses a very
high speed rotating diamond coated burr to abrade lesions into microparticles that are dispersed down stream;
it is very useful for heavily calcified lesions, but the consequences of distal embolization remain a considerable
concern. The transluminal endarterectomy catheter
(TEC) uses aspiration to collect debris shaved by a ro-
288
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Femoropopliteal Atherosclerotic Disease
tating cutting head and appears more effective in treating soft or thrombus-containing obstructions. In a
retrospective analysis of 35 SFAs treated with the transluminal endarterectomy catheter, the initial success rate
was 100%, but the 5-year patency was 0%.227 Both the
pullback atherectomy catheter and Redha-Cut (Sherine
Med AG) catheter rely on first passing the obstruction
with the entire device and then removing the material as
the catheter’s cutting blades are pulled back across the
lesion. In three prospective randomized trials, there was
no difference between angioplasty and atherectomy for
SFA disease.228-230 Initial ABI, but not tibial runoff or
long occlusions, appeared to be most predictive of patency after atherectomy.
Laser-assisted angioplasty
Laser-assisted angioplasty increases luminal crosssectional area by both athero-ablation and vessel expansion without calcium ablation.231,232 Technical success
with laser-assisted angioplasty is as high as 91%.233-235
There appears to be better initial recanalization with
laser-assisted angioplasty compared with PTA, but no
longterm differences between PTA and laser-assisted angioplasty have been appreciated.236,237 Enclosed thrombolysis associated with PTA has no advantage over PTA
alone.238
Brachytherapy
Delivery of radiation to the injured field in a vessel has
had beneficial effects. Endovascular radiotherapy can
prevent intimal hyperplasia after stent implantation in
femoropopliteal arteries,239 but it partially prevents healing of disrupted vessel surfaces.240 Gamma radiation
induces positive vascular remodeling after balloon angioplasty.241 When doses of 12 to 14 Gy (gamma radiation) are applied endoluminally to the femoropopliteal
segment after PTA, there is a twofold increase in 12month patency compared with that in untreated
controls.242-244 Similar results were noted in the Peripheral Artery Radiation Investigational Study trial.245
Cryotherapy
Cryoplasty is a novel therapy that combines conventional balloon angioplasty with application of cryotherapy. Experimental data suggest that cryotherapy induces
early arterial wall cell loss through apoptosis, but does
not alter intimal hyperplasia development or eventual
lumen area compared with conventional balloon angioplasty.246 The single system on the market at present uses
J Am Coll Surg
a double balloon system that exerts 8 atm on the lesion
and is accompanied by cold induced injury to the wall.
The hope is that cyrotherapy will allow more accurate
angioplasty and induce apoptosis in the wall, reducing
dissections and vessel response to injury. The final results
of the cryovascular safety registry have shown, in 102
patients, a primary patency of 82% at 10 months.247
Longer-term data are required, although case series suggest that improved patency can be achieved up to
18 months.248
Exercise versus angioplasty
Various trials have compared superficial femoral artery
PTA to exercise therapy. They suggest that although
PTA may give a short 3- to 6-month improvement in
symptoms, exercise therapy has better results at 12
months. But at 5-year followup, there appears to be no
difference between the groups.249-252 The loss of the initial advantage of PTA was attributable to restenosis of
the dilated segment; those treated conservatively had a
steadily increased benefit of exercise. The later loss of the
advantage of exercise was probably from a lack of adherence to the exercise program. The best effect of exercise
was found in patients with disease confined to the SFA
in contrast to PTA, which had the best effect in iliac
lesions.253 One study compared PTA with exercise with
no treatment and suggested that PTA moderately but
considerably improves quality of life at 1 year.254 All of
these studies lacked sufficient power and the seminal
group of PTA with supervised exercise is missing in all
studies.
Operation versus angioplasty
When examining the benefits of exercise in the claudicant population, another question arises: “Is there a
functional benefit of operation in the intermittent claudication population?” One study compared peripheral
bypass operation, operation followed by 6 months of
supervised exercise training with dynamic leg exercises,
and 6 months of supervised training alone in 75 patients
with claudication. At 13 months of randomization,
walking ability was improved in all three groups. The
most effective treatment for improving functional status
was exercise training plus operation. The median
changes in maximal walking distance were 173% for the
surgical group, 263% for the group that received both
supervised exercise and bypass, and 151% for the exercise group alone. The surgically treated patients increased their walking distance more than patients who
Vol. 201, No. 2, August 2005
Davies et al
Femoropopliteal Atherosclerotic Disease
289
in patients with disabling claudication and femoropopliteal stenosis or occlusion.
In conclusion, aggressive proactive medical therapy in
the claudicating patient remains the most important
therapeutic step that should be initiated as soon as claudication is identified (Fig. 5). Exercise is important in
this initial strategy, but will also contribute to improved
symptom relief in many patients. In patients who still
have severe lifestyle-limiting claudication that does not
respond to the initial medical regimen, angioplasty of
the SFA appears to be an appropriate intervention with
success more likely in low-grade lesions compared with
high-grade lesions. Adjuvants to a percutaneous approach have not proved consistently beneficial to date.
Endoluminal intervention without aggressive lifestyle
modifications is not recommended because the durability of the intervention is approximately 50% at 5 years
and secondary interventions are often required to maintain patency.
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Figure 5. A suggested therapeutic guideline for the patient presenting with claudication. Principal therapy must remain risk factor
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