Claudication: Treatment Options for Femoropopliteal Disease Martin Schillinger , Erich Minar ⁎

Progress in Cardiovascular Diseases 54 (2011) 41 – 46
www.onlinepcd.com
Claudication: Treatment Options for Femoropopliteal Disease
Martin Schillinger⁎, Erich Minar
Department of Angiology, Medical University, Vienna, Austria
Abstract
Intermittent claudication due to chronic femoropopliteal obstruction is a common disease, and
patients are potentially severely disabled by the painful limitation of walking capacity. Despite
major advances in pharmacological therapy of atherosclerosis, effective medication specifically
for treatment of intermittent claudication is still not available. Training programs work well for
patients with mild to moderate symptoms but frequently fail in patients with very compromised
walking capacity. Patients with severe symptoms and markedly reduced quality of life therefore
are candidates for revascularization. The preferred method of revascularization is endovascular
treatment; this includes simple balloon angioplasty, debulking techniques, stent implantation,
and, more recently, drug eluting technologies. Selected patients are candidates for surgery
which encompasses endarterectomy of focal common femoral lesions as well as
femoropopliteal bypass surgery in patients with very extensive disease or after failed
endovascular approaches. The following article reviews current aspects of the management of
femoropopliteal disease in patients with intermittent claudication. (Prog Cardiovasc Dis
2011;54:41-46)
© 2011 Elsevier Inc. All rights reserved.
Keywords:
Claudication; Femoropopliteal disease; Treatment
Intermittent claudication due to chronic femoropopliteal disease occurs relatively frequently in the population
60 years and older and can be a severely disabling
condition. Different treatment options are available,
depending on patients' symptoms and their reduction in
the quality of life. Irrespective of clinical stage, all
patients with peripheral artery disease require best
medical treatment to prevent complications of atherosclerosis; this includes platelet inhibitors, statins, and
usually antihypertensive and glucose-lowering medication. However, these medications have only a minor effect,
if any at all, on walking capacity, and only patients with
very mild symptoms will be adequately treated with these
medications only.
Statement of Conflict of Interest: see page 46.
⁎ Address reprint requests to Martin Schillinger, MD, Division of
Angiology, Department of Internal Medicine II, Vienna General Hospital,
Medical University, Waehringer Guertel 18-20, A-1090 Vienna, Austria,
Europe. Tel.: +43 1 40400 4670; fax: +43 1 40400 4665.
E-mail address: [email protected]
(M. Schillinger).
0033-0620/$ – see front matter © 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.pcad.2011.04.003
Walking training, particularly using supervision and
training programs, has tremendous effects in certain
subgroups of patients with intermittent claudication.
However, it frequently fails in patients with severely
limited walking capacity. The heterogeneous group of
vasoactive drugs is meant to improve peripheral perfusion,
but the net effect of most of these drugs has to be judged
very critically.
Patients with very short pain-free walking distance are
candidates for revascularization. However, the femoropopliteal segment is a challenging vascular territory. The
superficial femoral artery (SFA) is the longest artery in the
human body and is fixed between two major flexion points,
the hip and the knee. During movements like walking or
stair climbing, various forces are exerted on this vessel,
including flexion, longitudinal, and lateral compression
and torsion. Furthermore, the artery dives through a major
muscle group at the site of the Hunter's canal leading to
additional external compression during muscular work.
Differing from iliac arteries, the anatomy of the vascular
wall in the femoropopliteal segment is characterized by an
increased density of vascular smooth muscle cells.
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M. Schillinger, E. Minar / Progress in Cardiovascular Diseases 54 (2011) 41–46
Abbreviations and Acronyms
Response to injury by
extensive scar formation
CTO = Chronic total
leading to recurrent disocclusion
ease is a specific feature
of muscular arteries. Furthermore, particularly in the
femoropopliteal segment, atherosclerotic disease is usually
characterized by a diffuse and heavy calcification of long
vascular segments. Nevertheless, today, the preferred
method of revascularization in many patients is minimally
invasive endovascular treatment; this includes balloon
angioplasty, debulking techniques, stent implantation, and,
more recently, drug-eluting technologies. Whenever technically possible, endovascular treatment offers the advantage of low complication rates, short hospitalization, and
rehabilitation due to a low post-interventional morbidity
risk.1,2 The Achilles heel of endovascular treatment
remains long-term patency, particularly in patients with
certain risk factors and lesion morphologies. Selected
patients therefore are primarily candidates for surgery,
which includes endarterectomy and profundaplasty of
focal common femoral lesions as well as femoropopliteal
bypass surgery in patients with very extensive disease or
after failed endovascular approaches.1,2
Treatment options for claudicants with
femoropopliteal disease
Exercise training
Systematic exercise training has the potential to
dramatically improve patients' exercise capacity. Unstructured training—just based on the physician's recommendation to start walking—has very little or almost no effect
on the symptoms of intermittent claudication. Training
sessions should start with approximately 30 minutes and
then be increased to 1 hour. The intensity of the training
has to be structured to induce intermittent claudication in
3- to 5-minute intervals. Exercise is stopped at a level of
moderate claudication and resumed as soon as the pain is
gone. These cycles of exercise and rest should be between
35 and 50 minutes. Speed and treadmill grade can be
modified, but it is recommended to achieve a walking
speed of 3.0 mph (4.8 km/h) and then further increase the
grade. There are comorbid conditions which prohibit
training in 10% to 30% of the patients within studies. In
clinical practice, however, availability of the training
programs is the main limitation. A summary of the
evidence of exercise training in patients with intermittent
claudication is given in the TransAtlantic Inter-Society
Consensus II document.2
Vasoactive drugs
This is a very heterogeneous group of medication
meant to improve peripheral perfusion. A variety of drugs
are on the market, but very few have been proven effective
in randomized studies, Cilostazol is a phosphodiesterase
III inhibitor with vasodilator, metabolic and antiplatelet
activities. In a meta-analysis,3 the net effect of Cilostazol
is an improvement of walking capacity on the treadmill of
50 to 70 m; side-effects include head ache, diarrhea, and
palpitations. Cilostazol is contraindicated in patients with
congestive heart failure. Naftidrofuryl is a 5 hydroxtryptamine type 2 antagonist which may improve muscle
metabolism and reduce erythrocyte and thrombocyte
aggregation. A meta-analysis including 888 patients
showed a 26% improvement of walking capacity compared to placebo without significant increase of side
effects.4 Buflomedil was recently demonstrated in a single
randomized trial including 2078 patients with peripheral
artery disease to reduce cardiovascular events by 26% and
improve ankle-brachial index by 9% given over a 33month period.5
Prostanoids
The efficacy of prostanoids for patients with intermittent claudication is unclear. A Cochrane systematic review
identified 18 studies for this indication, but because of a
significant heterogeneity, no meta-analysis was possible.6
Intravenous administration of prostaglandin E1 improved
patients' walking capacity, whereas oral prostacyclin
analogs or intravenous prostacyclin was not effective in
patients with intermittent claudication.
For many other drugs, effectiveness has not been proven,
and therefore, these drugs are definitively not recommended.
Owing to overall minimal effects, in our personal
practice, the use of all vasoactive medication including the
drugs mentioned above in patients with intermittent
claudication is generally avoided.
Endovascular treatment
Patients with severe limitation of their walking capacity
and quality of life are definitively candidates for
revascularization procedures. Minimal invasive endovascular treatment offers several advantages, including the
extremely low mortality and morbidity of the procedures.
Its main limitation remains patency. Recently, significant
progress has been made in improving both recanalization
rates and midterm patency.
Recanalization technique
The use of dedicated chronic total occlusion catheters
currently enables recanalization of almost all lesions.
Personal experience and several reports from high-volume
centers confirm a success rate above 95% even in very long
and calcified femoropopliteal lesions using, for example,
the Outback Catheter System (Fig 1) (Cordis, Johnson&Johnson, New Brunswick, NJ). Additionally improved
chronic total occlusion wire technology and the use of
hydrophilic support catheters facilitate complex femoropopliteal procedures. Last but not least, advanced access
methods like transpopliteal or transpedal access routes help
M. Schillinger, E. Minar / Progress in Cardiovascular Diseases 54 (2011) 41–46
43
Fig 1. A, Angiographic occlusion (arrow) of the left superficial femoral artery (SFA). B, The outback catheter is advanced through the occlusion (arrow). C,
Angiogram of the recanalized proximal SFA. D, Angiogram of the distal recanalized SFA.
to guarantee successful outcomes in certain complex
anatomies.
Patency
Restenosis rate after femoropopliteal balloon angioplasty range between 40% in short lesions up to 80% in
long lesions at 12 months postintervention. Given this
fairly high failure rate particularly in lesions with a length
above 10cm the appropriateness of plain balloon angioplasty in this indication has to be questioned.
The application of nitinol stent technology significantly
improved the durability of stenting in intermediate length
femoropopliteal lesions. In the ABSOLUTE trial in 104
patients with severe claudication and 10 cm SFA stenosis
or occlusion, the restenosis rates were reduced from 63.5%
to 36.7% at 12 months by primary stenting (Fig 2), which
resulted also in a significantly improved walking capacity
on the treadmill.7 Nevertheless, a 2-year rate of restenosis
in the primary stent arm (46%) leaves room for
improvement.8 In contrast, the results of FAST (Femoral
Artery Stenting Trial) including 244 patients with a mean
lesion length between 4 and 5 cm showed no benefit of
primary stenting at 12 months (restenosis rate 32% vs.
39% in the stents vs the balloon angioplasty groups).9
Nevertheless, further studies like the RESILIENT and
ASTRON trials confirmed the initial results underlining
that nitinol stents improve midterm outcomes in intermediate-length lesions but remain a nonsatisfying treatment
option with respect to long term patency. Meanwhile,
initial problems with fractures of first generation nitinol
stents also were resolved.
Meanwhile, stent grafts have a renaissance as results of
these devices in extremely long lesions (average 25 cm)
were equivalent to prosthetic bypass surgery in recent
studies,10 and complication rates were dramatically
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Fig 2. Left panel shows a baseline left superficial femoral artery stenosis. Center panel shows the result of successful stent (arrows) placement. Right panel
shows 6 month follow-up angiography.
decreased due to lower profile introducer sizes. Nevertheless, it remains to be determined whether the mechanical
properties of these devices can withstand the forces
exerted in the femoropopliteal segment and whether the
problem of edge stenosis and subsequent stent graft
thrombosis can be resolved by an active (heparin) coating
of the devices.
Addressing alternative balloon technologies, after
failure of other balloon technologies such as cutting
balloon or cryoplasty, early studies with drug-eluting
balloons showed improved femoropopliteal patency rates
without leaving an implant in the vessel.11 In the 3-arm
THUNDER trial, 154 patients with short femoropopliteal
lesions (around 7 cm) were randomized to undergo either
plain balloon angioplasty with a standard balloon, balloon
angioplasty with a paclitaxel coated balloon, or with a
standard balloon and paclitaxel in the contrast medium.
Restenosis at 6 months was significantly reduced by the
paclitaxel eluting balloon (4%) compared to the standard
balloon groups with (29%) or without (37%) paclitaxel in
the contrast medium. Several studies are currently ongoing
to reproduce these promising results. Nevertheless, the
problems of elastic recoil, heavy calcification, and residual
stenosis after balloon angioplasty of long and complex
lesions likely cannot be resolved by the drug-coated
balloon approach.
In the field of promising technologies, drug-eluting
stents for long lesions generated hope for better outcomes
but, in fact, had very disappointing results. The SIROCCO
I study at 6 months12 showed 0% restenosis but even
together with SIROCCO II13 was underpowered to show a
benefit compared to the bare stent. The STRIDES study
was a single-arm prospective study using a more potent
everolimus eluting self-expanding stent and showed
disappointing 12 months of restenosis results, and the
product will not be further developed. So, until very
recently, drug-eluting stents in the femoropopliteal segment seemed a failure.
The 12-month results of the randomized ZILVER trial
included 479 patients with an average lesion length of 5 cm
who were randomized to balloon angioplasty versus
stenting using a polymer-free paclitaxel-eluting stent.
Patients in the balloon angioplasty group with a suboptimal
result after balloon only were further randomized to
secondary stenting using a bare or a drug-eluting stent.
Using a rather conservative definition of restenosis by
ultrasound (peak velocity ratio above 2.0), the paclitaxeleluting stent showed a significantly improved restenosis
rate at 12 months (17%) compared to optimal balloon
angioplasty (35%) as well as balloon angioplasty with
provisional stenting (33%). The stent had a very low 12month fracture rate (0.9%). It remains to be investigated
whether these results can be reproduced in all patient
subgroups and whether patency is maintained after long
follow-up. Currently, these results seem the best that can be
achieved in the femoropopliteal segment.
Biodegradable stents seem a concept worth being
further investigated. The main problem currently is the
unsatisfactory mechanical properties both of metallic
(magnesium-based) or polymeric-based biodegradable
materials. Radial force of the tested devices remains
problematic for the femoropopliteal segment, and true selfexpanding properties hardly can be achieved by the
current investigational devices.
M. Schillinger, E. Minar / Progress in Cardiovascular Diseases 54 (2011) 41–46
Surgery
Bypass surgery using vein grafts still gives the best
long-term results for long femoropopliteal lesions with
patency rates around 70% at 5 years.1,2 However, an
increased morbidity and mortality of the procedure as
compared to the endovascular approach always has to be
weighted against the good long-term results. Furthermore, data are less favorable if prosthetic graft material
has to be used. In these patients 5-year reocclusion rates
around 50% have to be expected.1 In personal practice,
patients' age and life expectancy and the operation risk
from a general medical perspective seem the most
important determinants whether a patient with a long
femoropopliteal lesion should primarily undergo surgery
or whether the endovascular approach is justified. Highly
calcified common femoral artery obstructions frequently
respond very poorly to endovascular treatment, in these
45
patients common femoral endarterectomy is the treatment
of choice.
Summary and conclusion
Treatment options for patients with intermittent claudication and femoropopliteal disease include pharmacologic
treatment and exercise training, endovascular therapy and
surgery (Fig 3). Best medical treatment is mandatory for all
patients with peripheral artery disease to beneficially
influence patients' overall prognosis. Patients with mild
or moderate claudication are, in the absence of contraindications, good candidates for supervised exercise training.
Patients with severe claudication and severe limitation of
their quality of life should undergo revascularization.
Endovascular treatment generally is the method of first
choice in these patients. Patients with long obstructions or
Fig 3. Treatment algorithm for patients with intermittent claudication due to femoropopliteal obstructions.
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after failure of endovascular procedures should be
considered for surgery.
6.
7.
Statement of Conflict of Interest
All authors declare that there are no conflicts of interest.
References
1. Dormandy JA, Rutherford RB: Management of peripheral arterial
disease (PAD). TASC Working Group. TransAtlantic Inter-Society
Consensus (TASC). J Vasc Surg 2000;31:S1-S296.
2. Norgren L, Hiatt WR, Dormandy JA, et al: Inter-Society Consensus
for the Management of Peripheral Arterial Disease (TASC II). J Vasc
Surg 2007;45:S5-S67.
3. Regensteiner J, Ware JJ, McCarthy W, et al: Effect of Cilostazol on
treadmill walking, community based walking ability and health
related quality of life in patients with intermittent claudication due to
peripheral arterial disease: a meta analysis of six randomized
controlled trials. J Am Geriatric Soc 2002;50:1939-1946.
4. Lehert P, Comte S, Gamand S, et al: Naftidrofuryl in intermittent
claudication: a retrospective analysis. J Cardiovasc Pharmacol
1994;23:S48-S52.
5. Limbs International Study Group: Oral buflomedil in the prevention
of cardiovascular events in patients with peripheral arterial obstruc-
8.
9.
10.
11.
12.
13.
tive disease: a randomized, placebo-controlled, 4-year study.
Circulation 2008;117:816-822.
Reiter M, Bucek RA, Stümpflen A, et al: Postanoids for intermittent
claudication. Cochrane Dataase Syst Rev 2004:CD000986.
Schillinger M, Sabeti S, Loewe C, et al: Balloon angioplasty versus
implantation of nitinol stents in the superficial femoral artery. N Engl
J Med 2006;354:1879-1888.
Schillinger M, Sabeti S, Dick P, et al: Sustained benefit at 2 years of
primary femoropopliteal stenting compared with balloon angioplasty
with optional stenting. Circulation 2007;15:2745-2749.
Krankenberg H, Schluter M, Steinkamp HJ, et al: Nitinol stent
implantation versus percutaneous transluminal angioplasty in
superficial femoral artery lesions up to 10 cm in length: the femoral
artery stenting trial (FAST). Circulation 2007;116:285-292.
Kedora J, Hohmann S, Garrett W, et al: Randomized comparison of
percutaneous Viabahn stent grafts vs. prosthethic femoropopliteal
bypass in the treatment of superficial femoral occlusive disease.
J Vasc Surg 2007;45:10-16.
Tepe G, Zeller T, Albrecht T, et al: Local delivery of paclitaxel to
inhibit restenosis during angioplasty of the leg. N Engl J Med
2008;358:689-699.
Duda SH, Pusich B, Richter G, et al: Sirolimus-eluting stents for the
treatment of obstructive superficial femoral artery disease: sixmonths results. Circulation 2002;106:1505-1509.
Duda SH, Bosiers M, Lammer J, et al: Sirolimus-eluting versus bare
nitinol stent for obstructive superficial femoral artery disease: the
SIROCCO II trial. J Vasc Interv Radiol 2005;16:331-338.