The Current State of Endovascular Intervention for Peripheral … · 2017-10-17 · CLINICAL REVIEW...
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CLINICAL REVIEW
Vascular Disease Management® October 2015 190
The Current State of Endovascular Intervention for Peripheral Arterial DiseaseRigved V. Tadwalkar, MD, MS; Michael S. Lee, MDFrom the UCLA Medical Center, Los Angeles, California.
ABSTRACT: The rising incidence of peripheral arterial disease (PAD) has resulted in a concomitant increase in
complications such as critical limb ischemia and lower-extremity amputation. Although a full spectrum of therapies
exists for femoropopliteal PAD, there is not yet a well-defined consensus on the role of a specific type of endovascular
modality that is best suited for treatment. Although percutaneous transluminal angioplasty (PTA) is commonly used
for revascularization in PAD due to high initial success rates of around 90%, long-term patency is a concern. Studies
comparing drug-eluting balloons to PTA have demonstrated encouraging results with respect to primary patency but
inconsistent results from the perspective of freedom from target lesion revascularization and adverse events. While
stent placement has primarily been utilized as “bail-out” therapy for PTA with complications, newer generation drug-
eluting stents including sirolimus-eluting and everolimus-eluting stents have shown favorable outcomes, suggesting
an increasing role for this form of percutaneous revascularization. Although a diverse array of atherectomy devices is
available, the role of these devices has yet to be clearly defined due to lack of high-quality studies that are appropriately
powered to evaluate for long-term clinical outcomes. Despite this, the continued study of these modalities complemented
by refinements in technique for new devices foreshadows a bright future for new endovascular approaches in the
treatment of PAD.
VASCULAR DISEASE MANAGEMENT 2015;12(10):E190-E203 Key words: peripheral vascular disease, drug-eluting stents, stenting, drug-eluting balloons,
atherectomy, critical limb ischemia
As life expectancy continues to increase, comor-
bidities that contribute to metabolic syndrome,
including diabetes mellitus, have become in-
creasingly prevalent. These comorbidities serve as
risk factors for the development of peripheral arte-
rial disease (PAD), resulting in complications such as
lifestyle-limiting claudication and critical limb isch-
emia (CLI). More than 200 million people are af-
fected by PAD worldwide, with nearly 27 million
of those individuals residing in North America and
Europe.1,2 The greater prevalence of PAD has caused a
concomitant increase in lower-extremity amputation
in the United States, with rise in rate from 19 to 30
amputations per 100,000 person-years over the past 2
decades.2,3
Treatment for PAD includes pharmacotherapy as
well as endovascular and surgical revascularization.
Percutaneous vascular intervention (PVI) is an effec-
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tive treatment option, particularly for patients with
type A or B TransAtlantic Inter-Society Consensus
(TASC II) disease, those with favorable anatomy to a
percutaneous approach, and those who are otherwise
poor surgical candidates.2,4 While a number of en-
dovascular modalities are available, a clear consensus
on the superiority of a particular type of treatment
has not yet emerged. We review the current data on
endovascular therapies for PAD.
BALLOON ANGIOPLASTYThe repeatability, low complication rate, and less in-
vasive nature of percutaneous transluminal angioplasty
(PTA) render this modality suitable for revasculariza-
tion for many lesions, especially those that are not
heavily calcified.5,6 The introduction of long balloons
allows for widespread use of PTA including for long le-
sions and patients with diffuse disease, especially given
the often multilevel and multivessel nature of PAD.
Initial success rates are in the 90% range for PTA of
the superficial femoral artery (SFA) and infrapopli-
teal arteries.7-9 However, long-term vessel patency is
a concern, with restenosis occurring in greater than
60% of cases at 12-month follow-up.9-12 Consequently,
reintervention is often required to restore patency. Re-
intervention for restenosis is associated with worsened
surgical outcomes as well as increased morbidity and
mortality, in part due to the high level of comorbidity
in the PAD patient population.13-15
DRUG-ELUTING BALLOONSDrug-eluting balloons (DEBs) are effective in the
coronary vasculature, particularly in small arteries and
bifurcation disease.16 Several studies have established
the benefit of DEB compared to PTA in primary pa-
tency for femoropopliteal disease.17-19 The LEVANT I
trial demonstrated the superiority of paclitaxel-coated
balloons (PCB) over PTA, with 58% less lumen loss at
6 months and similar safety profile to PTA.19 Lower
rates of target lesion revascularization (TLR) have also
been reported with PCB use.17,18
The 5-year results of the THUNDER trial dem-
onstrated lower rates of TLR with PCB as compared
to PTA (21% vs 56%; P=.0005) without significant
differences in adverse events, amputation rate, and
death.20 Similar positive results with PCB have been
reported in studies of patients undergoing PVI in the
infrapopliteal territory.21,22 The DEBATE-BTK trial
showed striking reductions in 1-year restenosis (27%
in DCB vs 74% in PTA; P<.001) and TLR (18% in
PCB vs 43% in PTA; P=.002) in diabetic patients
with high Rutherford-Becker class (greater than IV).22
However, the IN.PACT DEEP trial reported that the
Amphirion PCB (Medtronic) was noninferior to PTA
in terms of TLR and late lumen loss, but with a trend
toward increased complications including a higher
rate of major amputation at 12 months (8.8% vs 3.6%;
P=.080), resulting in withdrawal of the device from
the market.23
It has been difficult to ascertain why poor outcomes
were encountered in this trial, although excellent PTA
technique, inconsistent post-procedure wound care,
and the method in which IN.PACT Amphirion PCBs
are constructed leading to inconsistent paclitaxel dis-
tribution may be responsible for the lack of treatment
effect.23,24 The LEVANT II trial, a highly powered
54-site randomized control trial of 476 patients with
symptomatic intermittent claudication or ischemic
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pain while at rest and angiographically significant ath-
erosclerosis, showed greater primary patency rates for
those who had undergone angioplasty with a PCB as
opposed to PTA (65.2% vs 52.6%, P=.02) with non-
inferior safety outcomes at 12 months.25 However,
TLR and functional outcomes such as rates of rein-
tervention, thrombosis, amputation and were similar
among groups.25 In order to better clarify the role of
DEB in clinical practice, forthcoming studies should
explore head-to-head comparisons of DEB vs stent-
ing and atherectomy modalities.
STENTINGAlthough stent implantation has been utilized as a
“bail-out” treatment for some patients with residual
stenosis, significant recoil, and flow-limiting dissec-
tion after PTA, they are also used as primary therapy
with the hope of reducing the risk of restenosis.26
Self-expanding nitinol bare-metal stents (BMS) im-
prove outcomes compared to PTA in femoropopli-
teal arterial disease, even in complicated patients with
multiple comorbidities.27-30 A study of 104 patients
with femoropopliteal disease demonstrated the su-
periority of primary or secondary self-expanding ni-
tinol BMS placement compared to PTA in terms of
restenosis (49.2% vs 74.3%; P=.028) at 2 years.29 The
STROLL trial, a single-arm, multicenter study of 250
patients, revealed excellent results with the use of self-
expanding nitinol BMS for SFA disease (mean age
67.7±10.3 years, 47.2% with diabetes mellitus, mean
lesion length 77.3±35.3 mm) with 100% freedom
from 30-day major adverse events (death, index limb
amputation, and clinically driven TLR) with sustained
results at 12-month follow-up.31 Moreover, primary
stenting improved long-term clinical outcomes such
as ankle-brachial index (ABI) values and treadmill
walking capacity.29,31 Reassuring results have also been
obtained in studies involving infrapopliteal stenting. A
meta-analysis of patients undergoing both balloon-ex-
pandable and self-expandable BMS for infrapopliteal
disease showed satisfactory angiographic results, pa-
tency, and clinical outcomes over a 12-month period.32
By utilizing graft material to prevent intimal hy-
perplasia and reduce long-term restenosis, covered
stents were developed with the prospect of improving
pre-existing stent technology. Although early studies
of polyester-covered stent-grafts yielded poor results
because implantation was associated with low patency
rates and a significant post-procedural inflammatory
response, the use of expanded polytetrafluoroethyl-
ene (ePTFE)-covered stents has shown favorable out-
comes.33-36 The Viabahn Endoprosthesis (W. L. Gore
& Associates) is a non-heparin-bonded endoluminal
graft with an ePTFE lining and external nitinol sup-
port that was FDA approved in 2005 for SFA implanta-
tion. A number of investigators have studied this device
and have determined primary and secondary patency
rates ranging from 49% to 78.7% and 61% to 93.4%
respectively.37-40 In comparison to PTA, use of the Via-
bahn stent-graft has shown superior patency outcomes
at 12-month follow-up (65% vs 40%; P=.0003), with
an additional benefit for lesions ≥3cm in length.41 De-
spite these results, 36-month data from the VIBRANT
trial comparing Viabahn Endoprosthesis to bare niti-
nol stent implantation for severe SFA disease (TASC
C+D) revealed no significant difference in primary
or secondary patency rates between groups (24.2% vs
25.9%; P=.392 and 89.3% vs 79.5%; P=.304 respec-
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tively).42 Nevertheless, the Viabahn stent-graft frac-
tured less and both groups equally showed improve-
ment in hemodynamic and other quality measures.42
To account for concerns regarding edge restenosis
and stent thrombosis, the FDA approved a version of
the Viabahn device with a heparin-bonded surface
in 2007. Initial nonrandomized studies on the tech-
nology demonstrated improved biocompatibility by
affecting protein absorption and thromboresistance,
therefore extending patency time.43,44 The VIASTAR
trial, which evaluated 24-month outcomes of ePTFE-
covered stents to BMS in patients with symptomatic
peripheral arterial disease (PAD), found that patients
with long femoropopliteal lesions demonstrated sig-
nificantly higher primary patency rates in the heparin-
bonded covered stent group (63.1% vs 41.2%; P=.04),
but without a significant effect on freedom from TLR
(80.0% vs 61.9%; P=.13).45
The aSpire stent (LeMaitre Vascular) is another
covered-stent platform that is comprised of a nitinol
double-spiral body, allowing for better contour to the
vessel lumen and reduced obstruction of arterial side-
branches. Use of the aSpire stent has been shown to
have acceptable long-term results with primary cu-
mulative patency rate of 60.6% with a primary assisted
patency of 70.2% at 33 months in patients with long-
segment SFA occlusive disease.46 However, further ex-
perience with aSpire stenting reveals that a number of
reinterventions are often necessary to obtain optimal
patency results, suggesting the need for technologic
and pharmacologic improvements.47
The SIROCCO trial, which was the first dou-
ble-blinded, randomized controlled trial compar-
ing sirolimus-eluting stents (SES) to BMS in the
femoropopliteal distribution, along with a follow-up
study evaluating long-term outcomes found similar
rates of restenosis, TLR, ABI, and claudication symp-
toms between SES and BMS.48,49 The unexpectedly
low restenosis rate with BMS and suboptimal drug
elution of SES may account for the failure to dem-
onstrate superiority of SES in this trial.49
The Zilver PTX trial demonstrated a higher 5-year
primary patency rate with paclitaxel-eluting stents
compared with PTA or provisional BMS for SFA dis-
ease (66.4% vs. 43.4%).50-52 Enhancements pursued
in this trial, as compared to the SIROCCO trial, in-
cluded higher antiproliferative agent dosing density,
lack of binding polymer on the stent to reduce the risk
of delamination from repeated mechanical stress, and
importantly, PTA with subsequent “bail-out” stent-
ing as a choice for the control arm.51 Criticisms of
this trial included the relatively short lesions lengths.
Other stent platforms, including the Dynalink nitinol
self-expanding stent (Abbott Vascular), which uses an
everolimus-eluting stent (EES) with a longer elution
profile, have also established favorable outcomes and
clinical improvements for femoropopliteal arterial dis-
ease, although an even longer drug-elution profile may
be necessary for patients with longer lesions given the
high number of restenosis events encountered in this
study after 6 months.51,53
Data from clinical trials reveal that the treatment of
infrapopliteal disease with drug-eluting stents (DES)
leads to significantly greater patency rates when com-
pared to PTA or BMS.54 The ACHILLES trial, which
included 200 patients with infrapopliteal disease, dem-
onstrated higher primary patency rates with SES (80.6%
vs 58.1%; P=.006) and lower TLR rates (10% vs 16.5%;
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P=.26) compared with PTA.55 The YUKON-BTK and
DESTINY trials have shown superiority in primary
lumen patency at 12-month follow-up of SES and EES
as compared to BMS, respectively (80.6% in SES vs
55.6% in BMS; P<.05 and 85.2% in EES vs 54.4% in
BMS; P<.05).56,57 A review of 18 nonrandomized stud-
ies comparing SES to BMS show superiority of SES
in the prevention of restenosis (P<.001) and also show
superiority of SES to paclitaxel-eluting stents with re-
gard to primary patency and need for revascularization
at 12 months (P=.014).32
A single prospective study evaluating EES to PTA
with provisional BMS placement in lesions >4.5 cm
showed higher primary patency with EES vs PTA/
BMS (29.7% vs 20.6%; P<.0001) as well as improved
event-free survival (hazard ratio 2.2, 95% confidence
interval 1.2-4.1, P=.015), demonstrating that patients
with longer lesions can also benefit from EES.58 How-
ever, a retrospective dual-center study comparing DEB
to DES for 228 patients of all Rutherford-Becker classes
with long lesions (>10 cm) found similar rates of binary
restenosis (23.9% vs 30.4%; P=.319) and TLR (15.6%
vs 19.0%; P=.543).59
ATHERECTOMYSeveral types of atherectomy devices are available for
plaque modification and debulking (Table 1). Exci-
sional atherectomy utilizes an intra-arterial blade to
remove plaque from the arterial wall (Figure 1). An
Table 1. A Comparison of Major Atherectomy Systems for Use in the Peripheral Vasculature
Device Manufacturer Category Design Proposed Advantage
SilverHawk Plaque Excision System Medtronic/Covidien Excisional
Single-blade directional cutting
Lessened vessel trauma
TurboHawk Plaque Excision System
Medtronic/Covidien ExcisionalMultiple-blade contoured cutting
Greater directional control
Rotablator System Boston Scientific RotationalRotating brass burr with diamond crystals
Differential cutting
Jetstream Atherectomy System Boston Scientific
Rotational /aspirational
Rotating front cutting Continuous aspiration
Diamondback 360 Peripheral Orbital Atherectomy System
Cardiovascular Systems Inc.
OrbitalBidirectional eccentric crown
Plaque modification
CVX-300 Excimer Laser Spectranetics Laser/ablativeBeam of light with photochemical lytic effect
Pulsed energy ablation
Figure 1. Excisional atherectomy utilizes an intra-arterial blade to remove plaque from the arterial wall.
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advantage to this approach as compared to other en-
dovascular interventions includes the ability to maxi-
mize luminal gain by directing treatment toward the
target lesion, even when those lesions are re-stenotic
or excessively calcified.60-62 The initial outcomes from
studies that employed atherectomy were encouraging
but were not considerably different than PTA, thus
limiting use of this technology early on.63 Subsequent
studies of excisional atherectomy have demonstrated
variable primary patency rates at 12 months (43% to
84%) with even poorer rates in re-stenotic lesions.64-66
Moreover, worsening patency and restenosis rates
have been observed in patients with more significant
disease (TASC C+D). A retrospective analysis of pa-
tients with symptomatic lower-limb PAD undergoing
atherectomy with the TurboHawk atherectomy device
(Medtronic/Covidien) by a single clinician on 47 ves-
sels demonstrated 6- and 12-month patency rates of
72.6% and 58.9%, respectively.67 When atherectomy
was assisted by other measures, the primary patency
rate was 93.2% and 74.6% at 6 months and 12 months,
respectively.67 Notably, patients in the earlier cohort
had a patency rate of 41.3% as compared to 82.9% for
patients in the latter cohort (P=.001), indicating that
there may be a learning curve associated with usage
of directional atherectomy.67 Furthermore, the initial
cases included aggressive atherectomy over longer seg-
ments whereas patients near the end of the series were
treated more conservatively over shorter segments.
Rotational atherectomy involves the use of a con-
centrically spinning burr in association with a drive
shaft and turbine.68 The proposed advantage of rota-
tional atherectomy is “differential cutting,” where the
device atherectomizes the diseased inelastic plaque as
opposed to healthy elastic tissue, as well as the abil-
ity to better advance the burr through narrowed and
calcified vessels. Although high initial success rates
have been achieved with the use of rotational ather-
ectomy vs PTA in the coronary circulation (89% vs
80%; P=.0019), TLR is increased (42.4% vs 31.9%;
P=.013).69 Follow-up multicenter data demonstrate
similar lack of benefit in the prevention of restenosis,
limiting use of rotational atherectomy as pretreatment
for heavily calcified lesions prior to stenting.70 Cur-
rently, rotational atherectomy with devices like the
Rotablator (Boston Scientific) is rarely used for PVI.
Improvements to rotational atherectomy technology,
as developed for the Jetstream Atherectomy System
(Boston Scientific), allow for thrombectomy along
with rotational atherectomy from the same catheter
as well as continual active aspiration for the removal
of debris (Figure 2).71 Although a single-center study
utilizing this system revealed 99% device success with
clinically driven TLR rate of 26% at 1 year, a large
Figure 2. The Jetstream Atherectomy System (Boston Scientific) allows for thrombectomy along with rotational atherectomy from the same catheter as well as continual active aspiration for the removal of debris.
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review evaluating this system along with a similar device
showed a combined distal embolization rate of 22% vs
1.9% with excisional atherectomy, vs 0.9% with PTA alone,
and 0.7% with PTA followed by stenting.72,73
Operating with a crown similar to the rotational ather-
ectomy burr, orbital atherectomy (Diamondback 360°
Peripheral Orbital Atherectomy System; Cardiovascular
Systems, Inc.) employs an orbiting action to modify plaque
as well as increase lumen size (Figure 3).74-77 Prospective,
multicenter data evaluating the use of orbital atherectomy
demonstrated that shorter spin times and smaller crown
sizes significantly lowered procedural complications, in-
cluding spasm, embolism, and slow flow, thus underscoring
the importance of technique optimization in utilizing this
device.75 Orbital atherectomy followed by balloon angio-
plasty compared to PTA alone in infrapopliteal disease
demonstrated better procedural success (93.1% vs
82.4%; P=.27) with less bail-out stenting and greater
freedom from target vessel revascularization (TVR)
(93.3% vs 80.0%; P=.14).76 A similar study comparing
orbital atherectomy followed by PTA with PTA alone
in calcified femoropopliteal disease showed freedom
from TLR or restenosis of 77.1% vs 11.5% at 6 months
(P<.001), inferring that plaque debulking with orbital
atherectomy seems to increase the chance of attaining
a desirable angioplasty result.77
Laser technology has also been utilized for the ex-
perimental ablation of atherosclerosis for decades.78
Although previous iterations of laser technology re-
sulted in excessive thermal injury due to continuous
power output, xenon chloride excimer laser delivers
pulsed energy over a shorter period of time, allow-
ing for ablation with less restenosis and thrombosis.79
The LACI trial, a prospective trial involving guide-
wire traversal and excimer laser angioplasty followed
by PTA with optional stenting in patients who were
poor candidates for bypass surgery, reported procedural
success in 86% of treated lesions, with limb salvage
of 92% at 6 months.80 The 8 Fr Turbo-Booster laser
guide catheter (Spectranetics Corporation) allows for
directional ablation along multiple planes resulting
in more targeted ablation (Figure 4).81 The CELLO
Figure 3. Orbital atherectomy (A) employs an orbiting action of a crown to modify plaque as well as increase lumen size (B).
A B
Figure 4. The Turbo-Booster laser guide catheter (Spectranetics Corporation) allows for directional ablation along multiple planes, resulting in more targeted ablation.
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study revealed patency rates of 59% and 54% at 6
months and 12 months, respectively, and total TLR
of 23.1% at 1 year for femoropopliteal lesions.81 A
retrospective review of patients with both lower limb
claudication and CLI evaluating for hard clinical
endpoints underscore the need for an appropriately
selected patient when intervening with laser atherec-
tomy, because negative outcomes are seen in patients
with comorbidities such as renal failure and diabetes
mellitus, even when initial success rates are high.82
Although atherectomy is a promising interventional
modality, a Cochrane Collaboration meta-analysis in-
cluding a total of 220 patients has established that there
is no clear evidence to currently support atherectomy
over PTA for the outcome of primary patency over any
interval of time.83 Additionally, the quality of evidence
on atherectomy is poor, because randomized controlled
trials that have been performed thus far are nonblinded,
improperly powered, and have limited data on adverse
events, making the true outcomes of this modality im-
precise.83
Other technologies, such as cryoplasty, may play an
adjunctive role in PVI. In a prospective, randomized,
multicenter clinical trial of 74 diabetic patients with
90 SFA lesions undergoing BMS placement followed
by postdilation using cryoplasty balloon vs conven-
tional PTA, binary restenosis was significantly lower
in the cryoplasty group (29.3% vs 55.8%; P=.01).84
A meta-analysis of 1,090 patients demonstrated that
brachytherapy, which involves the application of ra-
diation directly to the site of vessel narrowing after
treatment, may be a useful adjunct for the purpose
of maintaining patency and preventing restenosis.85
ECONOMIC CONSIDERATIONSA physician study group on behalf of The Society
for Cardiovascular Angiography and Interventions
(SCAI) systematically reviewed the economics of the
various endovascular modalities in PAD by using a
Markov model to estimate the 24-month budget im-
pact of index procedures and reinterventions in the
United States.86 Index procedures were PTA, DEB,
BMS, and DES while atherectomy was only considered
as a technique for reintervention given the interest in
noncomplex lesions for the analysis. Given the lack
of generalizable evidence, there was no differentiation
among the different atherectomy catheters.
A number of assumptions about the model were
made for the purpose of the analysis. The choice of
therapy in reintervention was based on the opinion
of the authors, only one reintervention was allowed
during the 24-month period, only one device was as-
sumed to be used during an intervention, an assump-
tion was made that stent-based or DCB procedures
would implicate the use of an uncoated balloon for
predilation, and amputations or deaths were not ac-
counted for. Cost assumptions were also made.
The Medicare reimbursement rate for revascular-
ization with DEB was assumed to be similar to PTA
because DEB is not yet approved in the United States,
and the reimbursement rate for revascularization with
a DES was assumed to be similar to BMS because
no separate reimbursement exists as of yet for these
devices. Reimbursement rates were determined by
2013 national fiscal data for PVI. Also, a mix-adjusted
average of Medicare severity diagnosis related groups
(MS-DRGs) was used, with 50% of the procedures
assumed to be performed in the inpatient setting. A
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total of 13 studies with 2,406 patients were included
in this analysis. The average cost per patient over 24
months, including the cost of the index procedure
and the possible cost of reintervention was lowest
for DEB ($10,214) followed by DES ($12,904), PTA
($13,114) and BMS ($13,802). In their analysis, which
also looked at clinical effectiveness, DEB and DES
compared favorably to PTA and BMS from the per-
spective of 24-month TLR, with number-needed-to-
treat in the 4 to 7 range per TLR avoided. On the basis
of these data, drug-eluting strategies and particularly
DEBs offer the lowest budget impact and highest eco-
nomic value when concurrently accounting for clinic
effectiveness. However, due to the assumptions made
for the analysis, the results should be interpreted with
caution.
LIMITATIONS OF CURRENT DATA While developments in the field of endovascular in-
tervention have exciting implications, the heterogene-
ity of the available literature makes drawing definitive
conclusions difficult. Many of the studies have been
limited by design, including varying study size, study
population, study location, type of imaging technique
used, site of intervention, as well as the duration and
intensity of antithrombotic use, all lending to a lack
of gold-standard evidence. Operator and author inter-
pretation of patient cases and preferences for treatment
also produce bias that ultimately affects outcome data.
Further, the use of disparate endpoints including pa-
tency, limb salvage, TLR, TVR, and freedom from
reintervention makes the direct comparison of modali-
ties problematic. Even with many of these limitations
accounted for, it remains to be seen whether enhanced
outcomes beyond 12 to 24 months without excess
adverse events can be accomplished. While higher-
quality studies are required to establish the genuine
efficacy of these evolving modalities, improvements
in device quality and technical expertise will be es-
pecially beneficial.
CONCLUSIONThe current landscape for PVI includes various
technologies that may improve clinical outcomes in
PAD. The use of DEB increases patency and TLR
outcomes in both femoropopliteal and infrapopliteal
PAD. Stenting has a rising role in both bail-out and
primary interventions and is particularly promising
with the development of DES. The proposed advan-
tages of atherectomy have not yet reliably translated
into improved clinical outcomes, although the ef-
fectiveness of this approach will increase with tech-
nique optimization, refinement of the technology,
and further study. Although the guidelines currently
support PVI, particularly PTA with bail-out stenting
conclusively in patients in a low TASC category who
are otherwise not surgical candidates, further study
of these emerging technologies in well-designed and
highly powered trials are needed to determine the
ideal treatment strategies for the management of pa-
tients with PAD. n
Editor’s note: Disclosure: The authors have completed
and returned the ICMJE Form for Disclosure of Potential
Conflicts of Interest. The authors report no disclosures related
to the content herein.
Manuscript received March 4, 2015; provisional acceptance
given June 15, 2015; manuscript accepted July 9, 2015.
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Address for correspondence: Michael S. Lee, MD, 100
Medical Plaza, Suite 630, Los Angeles, CA 90095,
United States. E-mail: [email protected].
REFERENCES1. Fowkes FG, Rudan D, Rudan I, et al. Comparison of
global estimates of prevalence and risk factors for pe-ripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013;382(9901):1329-1340.
2. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG; TASC II Working Group. In-ter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45 Suppl S:S5-S67.
3. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mes-enteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Soci-ety for Vascular Medicine and Biology, Society of In-terventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Pe-ripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabili-tation; National Heart, Lung, and Blood Institute; So-ciety for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. J Am Coll Cardiol. 2006;47(6):1239-1312.
4. Anderson JL, Halperin JL, Albert NM, et al. Manage-ment of patients with peripheral artery disease (com-pilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology Foundation/American Heart Associa-tion Task Force on Practice Guidelines. Circulation. 2013;127(13):1425-1443.
5. Laird JR. Limitations of percutaneous transluminal an-gioplasty and stenting for the treatment of disease of the superficial femoral and popliteal arteries. J Endovasc Ther. 2006;13(Suppl II):II30-II40.
6. Ansel GM, Lumsden AB. Evolving modalities for femo-ropopliteal interventions. J Endovasc Ther. 2009;16(Suppl
II):II82-II97.7. Lo RC, Darling J, Bensley RP, et al. Outcomes follow-
ing infrapopliteal angioplasty for critical limb ischemia. J Vasc Surg. 2013;57(6):1455-1463.
8. Baumann F, Willenberg T, Do DD, Keo HH, Baumgartner I, Diehm N. Endovascular revasculariza-tion of below-the-knee arteries: prospective short-term angiographic and clinical follow-up. J Vasc Interv Radiol. 2011;22(12):1665-1673.
9. Dormandy JA, Rutherford RB. Management of periph-eral arterial disease (PAD). J Vasc Surg. 2000;31:S1-S296.
10. Johnston KW. Femoral and popliteal arteries: re-analysis of results of balloon angioplasty. Radiology. 1992:183(3):767-771.
11. Minar E, Pokrajac B, Maca T, et al. Endovascular brachytherapy for prophylaxis of restenosis after femo-ropopliteal angioplasty: results of a prospective ran-domized study. Circulation. 2000;102(22):2694-2699.
12. Schmidt A, Ulrich M, Winkler B, et al. Angiographic patency and clinical outcome after balloon-angioplasty for extensive infrapopliteal arterial disease. Catheter Cardiovasc Interv. 2010;76(7):1047-1054.
13. Conte MS, Geraghty PJ, Bradbury AW, et al. Suggest-ed objective performance goals and clinical trial design for evaluating catheter-based treatment of critical limb ischemia. J Vasc Surg. 2009;50(6):1462-1473.
14. Iida O, Soga Y, Kawasaki D, et al. Angiographic reste-nosis and its clinical impact after infrapopliteal angio-plasty. Eur J Vasc Endovasc Surg. 2012;44(4):425-431.
15. Bradbury AW, Adam DJ, Bell J, et al.; BASIL Trial Participants. Bypass versus Angioplasty in Severe Isch-aemia of the Leg (BASIL) trial: A survival prediction model to facilitate clinical decision making. J Vasc Surg. 2010;51(5 Suppl):52S-68S.
16. Latib A, Colombo A, Castriota F, et al. A random-ized multicenter study comparing a paclitaxel drug-eluting balloon with a paclitaxel-eluting stent in small coronary vessels: the BELLO (Balloon Elution and Late Loss Optimization) study. J Am Coll Cardiol. 2012;60(24):2473-2480.
17. Micari A, Cioppa A, Vadalà G, et al. Clinical evalu-ation of a paclitaxel-eluting balloon for treatment of femoropopliteal arterial disease: 12-month results from a multicenter Italian registry. JACC Cardiovasc Interv. 2012 Mar;5(3):331-338.
18. Tepe G, Zeller T, Albrecht T, et al. Local delivery of
Copyri
ght H
MP Com
munica
tions
CLINICAL REVIEW
Vascular Disease Management® October 2015 200
paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med. 2008;358(7):689–699.
19. Scheinert D, Duda S, Zeller T, et al. The LEVANT I (Lutonix paclitaxel-coated balloon for the prevention of femoropopliteal restenosis) trial for femoropopliteal revascularization: first-in-human randomized trial of low-dose drug-coated balloon versus uncoated balloon angioplasty. JACC Cardiovasc Interv. 2014;7(1):10–19.
20. Tepe G, Schnorr B, Albrecht T, et al. Angioplasty of Femoral-Popliteal Arteries With Drug-Coated Bal-loons: 5-Year Follow-Up of the THUNDER Trial. JACC Cardiovasc Interv. 2015;8(1 Pt A):102-108.
21. Schmidt A, Piorkowski M, Werner M, et al. First experience with drug-eluting balloons in infrapopliteal arteries restenosis rate and clinical outcome. J Am Coll Cardiol. 2011;58(11):1105–1109.
22. Liistro F, Porto I, Angioli P, et al. Drug-Eluting Bal-loon in Peripheral Intervention for Below the Knee Angioplasty Evaluation (DEBATE-BTK): a random-ized trial in diabetic patients with critical limb isch-emia. Circulation. 2013;128(6):615–621.
23. Zeller T, Baumgartner I, Scheinert D, et al.; IN.PACT DEEP Trial Investigators. Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP randomized trial. J Am Coll Cardiol. 2014;64(15):1568-1576.
24. Laird JR, Armstrong EJ. Drug-coated balloons for infrapopliteal disease: digging deep to understand the impact of a negative trial. J Am Coll Cardiol. 2014;64(15):1577-1579.
25. Rosenfield K, Jaff MR, White CJ, et al.; LEVANT 2 Investigators. Trial of a Paclitaxel-Coated Balloon for Femoropopliteal Artery Disease. N Engl J Med. 2015;373(2):145-153.
26. Yang X, Lu X, Ye K, Li X, Qin J, Jiang M. Systematic review and meta-analysis of balloon angioplasty versus primary stenting in the infrapopliteal disease. Vasc En-dovascular Surg. 2014;48(1):18-26.
27. Hiro R, Leung CY, de Guzman S, Gordon IL, Conroy RM, Tobis JM. A comparison of balloon angioplasty and self-expandable stent treatment of occluded super-ficial femoral arteries. Circulation. 1995;92(8):1–56.
28. Schillinger M, Sabeti S, Loewe C, et al. Balloon angio-plasty versus implantation of nitinol stents in the super-ficial femoral artery. N Engl J Med. 2006;354(18):1879-
1888. 29. Schillinger M, Sabeti S, Dick P, et al. Sustained benefit
at 2 years of primary femoropopliteal stenting com-pared with balloon angioplasty with optional stenting. Circulation. 2007;115(21):2745-2749.
30. Soga Y, Iida O, Hirano K, Yokoi H, Nanto S, Nobuy-oshi M. Mid-term clinical outcome and predictors of vessel patency after femoropopliteal stenting with self-expandable nitinol stent. J Vasc Surg. 2010;52(3):608–615.
31. Gray WA, Feiring A, Cioppi M, et al.; STROLL Study Investigators. S.M.A.R.T. Self-Expanding Niti-nol Stent for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery (STROLL): 1-Year Outcomes. J Vasc Interv Radiol. 2015;26(1):21-28.
32. Biondi-Zoccai GG, Sangiorgi G, Lotrionte M, et al. Infragenicular stent implantation for below-the-knee atherosclerotic disease: clinical evidence from an inter-national collaborative meta-analysis on 640 patients. J Endovasc Ther. 2009;16(3):251-260.
33. Link J, Müller-Hülsbeck S, Brossmann J, Steffens JC, Heller M. Perivascular inflammatory reaction after percutaneous placement of covered stents. Cardiovasc Intervent Radiol. 1996;19(5):345-347.
34. Maynar M, Reyes R, Ferral H, et al. Cragg Endopro System I: early experience. I. Femoral arteries. J Vasc Interv Radiol. 1997;8(2):203-207.
35. Saxon RR, Coffman JM, Gooding JM, Ponec DJ. Long-term patency and clinical outcome of the Via-bahn stent-graft for femoropopliteal artery obstructions. J Vasc Interv Radiol. 2007;18(11):1341-1349.
36. Alimi YS, Hakam Z, Hartung O, et al. Efficacy of Viabahn in the treatment of severe superficial femoral artery lesions: which factors influence long-term paten-cy? Eur J Vasc Endovasc Surg. 2008;35(3):346-352.
37. Lammer J, Dake MD, Bleyn J, et al. Peripheral arte-rial obstruction: prospective study of treatment with a transluminally placed self-expanding stent-graft. Inter-national Trial Study Group. Radiology. 2000;217(1):95-104.
38. Deutschmann HA, Schedlbauer P, Bérczi V, Portu-galler H, Tauss J, Hausegger KA. Placement of He-mobahn stent-grafts in femoropopliteal arteries: early experience and midterm results in 18 patients. J Vasc Interv Radiol. 2001;12(8):943-950.
39. Railo M, Roth WD, Edgren J, et al. Preliminary re-
Copyri
ght H
MP Com
munica
tions
CLINICAL REVIEW
Vascular Disease Management® October 2015 201
sults with endoluminal femoropopliteal thrupass. Ann Chir Gynaecol. 2001;90(1):15-18.
40. Kedora J, Hohmann S, Garrett W, Munschaur C, Theune B, Gable D. Randomized comparison of per-cutaneous Viabahn stent grafts vs prosthetic femoral-popliteal bypass in the treatment of superficial femoral arterial occlusive disease. J Vasc Surg. 2007;45(1):10-16.
41. Saxon RR, Dake MD, Volgelzang RL, Katzen BT, Becker GJ. Randomized, multicenter study com-paring expanded polytetrafluoroethylene-covered endoprosthesis placement with percutaneous trans-luminal angioplasty in the treatment of superficial femoral artery occlusive disease. J Vasc Interv Radiol. 2008;19(6):823-832.
42. Geraghty PJ, Mewissen MW, Jaff MR, Ansel GM; VI-BRANT Investigators. Three-year results of the VI-BRANT trial of VIABAHN endoprosthesis versus bare nitinol stent implantation for complex superficial femoral artery occlusive disease. J Vasc Surg. 2013;58(2):386-395.
43. Peeters P, Verbist J, Deloose K, Bosiers M. Results with heparin bonded polytetrafluoroethylene grafts for femorodistal bypasses. J Cardiovasc Surg (Torino). 2006;47(4):407-413.
44. Bosiers M, Deloose K, Verbist J, et al. Heparin-bonded expanded polytetrafluoroethylene vascular graft for femoropopliteal and femorocrural bypass grafting: 1-year results. J Vasc Surg. 2006;43(2):318-319.
45. Lammer J, Zeller T, Hausegger KA, et al. Sustained benefit at 2 years for covered stents versus bare-metal stents in long SFA lesions: the VIASTAR trial. Cardio-vasc Intervent Radiol. 2015;38(1):25-32.
46. Rosenthal D, Martin JD, Smeets L, et al. Remote superficial femoral artery endarterectomy and dis-tal aSpire stenting: results of a multinational study at three-year follow-up. J Cardiovasc Surg (Torino). 2006;47(4):385-391.
47. Lenti M, Cieri E, De Rango P, et al. Endovascular treatment of long lesions of the superficial femoral artery: results from a multicenter registry of a spiral, covered polytetrafluoroethylene stent. J Vasc Surg. 2007;45(1):32-39.
48. Duda SH, Bosiers M, Lammer J, et al. Sirolimus-elut-ing versus bare nitinol stent for obstructive superficial femoral artery disease: the SIROCCO II trial. J Vasc Interv Radiol. 2005;16(3):331-338.
49. Duda SH, Bosiers M, Lammer J, et al. Drug-eluting
and bare nitinol stents for the treatment of atheroscle-rotic lesions in the superficial femoral artery: long-term results from the SIROCCO trial. J Endovasc Ther. 2006;13(6):701-710.
50. Dake M. The Zilver PTX randomized trial of treating femoropopliteal artery disease: 5-year results. Presented at: Vascular Interventional Advances (VIVA); Novem-ber 4-7, 2014; Las Vegas, NV.
51. Walker JP, Owens CD. Current Status of Drug-Elut-ing Stents and Drug-Eluting Balloons for the Superfi-cial Femoral Artery. Curr Surg Rep. 2013;1(2):90-97.
52. Dake MD, Ansel GM, Jaff MR, et al; Zilver PTX Investigators. Sustained safety and effectiveness of paclitaxel-eluting stents for femoropopliteal lesions: 2-year follow-up from the Zilver PTX randomized and single-arm clinical studies. J Am Coll Cardiol. 2013;61(24):2417-2427.
53. Lammer J, Bosiers M, Zeller T, et al. First clinical trial of nitinol self-expanding everolimus-eluting stent implantation for peripheral arterial occlusive disease. J Vasc Surg. 2011;54(2):394-401.
54. Rastan A, Noory E, Zeller T. Drug-eluting stents for treatment of focal infrapopliteal lesions. Vasa. 2012;41(2):90-05.
55. Scheinert D, Katsanos K, Zeller T, et al; ACHILLES Investigators. A prospective randomized multicenter comparison of balloon angioplasty and infrapopliteal stenting with the sirolimus-eluting stent in patients with ischemic peripheral arterial disease: 1-year re-sults from the ACHILLES trial. J Am Coll Cardiol. 2012;60(22):2290-2295.
56. Rastan A, Tepe G, Krankenberg H, et al. Sirolimus-eluting stents vs. bare-metal stents for treatment of focal lesions in infrapopliteal arteries: a double-blind, multi-centre, randomized clinical trial. Eur Heart J. 2011;32(18):2274-2281.
57. Bosiers M, Scheinert D, Peeters P, et al. Random-ized comparison of everolimus-eluting versus bare-metal stents in patients with critical limb ischemia and infrapopliteal arterial occlusive disease. J Vasc Surg. 2012;55(2):390-398.
58. Karnabatidis D, Spiliopoulos S, Diamantopoulos A, et al. Primary everolimus-eluting stenting versus balloon angioplasty with bailout bare metal stenting of long infrapopliteal lesions for treatment of critical limb isch-emia. J Endovasc Ther. 2011;18(1):1-12.
Copyri
ght H
MP Com
munica
tions
CLINICAL REVIEW
Vascular Disease Management® October 2015 202
59. Zeller T, Rastan A, Macharzina R, et al. Drug-coated balloons vs. drug-eluting stents for treatment of long femoropopliteal lesions. J Endovasc Ther. 2014;21(3):359-368.
60. Laird JR. Endovascular treatment of common femoral artery disease viable alternative to surgery or just another short-term fix. J Am Coll Cardiol. 2011;58(8):799-800.
61. Henry M, Klonaris C, Amor M, Henry I, Tzveta-nov K. State of the art: which stent for which le-sion in peripheral interventions? Tex Heart Inst J. 2000;27(2):119-126.
62. Laird JR, Yeo KK. The treatment of femoropopliteal in-stent restenosis: back to the future. J Am Coll Car-diol. 2012;59(1):24-25.
63. Höfling B, Pölnitz AV, Backa D, et al. Percutaneous removal of atheromatous plaques in peripheral arteries. Lancet. 1988;1(8582):384-386.
64. Zeller T, Rastan A, Sixt S, et al. Long-term results af-ter directional atherectomy of femoro-popliteal lesions. J Am Coll Cardiol. 2006;48(8):1573-1578.
65. Biskup NI, Ihnat DM, Leon LR, Gruessner AC, Mills JL. Infrainguinal atherectomy: a retrospective review of a single-center experience. Ann Vasc Surg. 2008;22(6):776-782.
66. Sarac TP, Altinel O, Bannazadeh M, Kashyap V, Lyden S, Clair D. Midterm outcome predictors for lower extremity atherectomy procedures. J Vasc Surg. 2008;48(4):885-890.
67. Werner-Gibbings K, Dubenec S. Short-term outcomes of excisional atherectomy in lower limb arterial disease. ANZ J Surg. 2014 Nov 3. [Epub ahead of print]
68. Spencer B, Yeung AC. Rotational atherectomy: con-cepts and practice. In: Interventional Cardiology. New York: McGraw-Hill; 2007:333-347.
69. Reifart N, Vandormael M, Krajcar M, et al. Random-ized comparison of angioplasty of complex coronary lesions at a single center. Excimer Laser, Rotational Atherectomy, and Balloon Angioplasty Comparison (ERBAC) Study. Circulation. 1997;96(1):91-98.
70. Tran T, Brown M, Lasala J. An evidence-based ap-proach to the use of rotational an directional coro-nary atherectomy in the era of drug-eluting stents: when does it make sense? Catheter Cardiovasc Interv. 2008;72(5):650-662.
71. Zeller T, Krankenberg H, Rastan A, et al. Percutane-
ous rotational and aspiration atherectomy in infraingui-nal peripheral arterial occlusive disease: a multicenter pilot study. J Endovasc Ther. 2007;14(3):357-364.
72. Zeller T, Krankenberg H, Steinkamp H, et al. One-year outcome of percutaneous rotational atherectomy with aspiration in infrainguinal peripheral arterial oc-clusive disease: the multicenter pathway PVD trial. J Endovasc Ther. 2009;16(6):653-662.
73. Shrikhande GV, Khan SZ, Hussain HG, Dayal R, McKinsey JF, Morrissey N. Lesion types and device characteristics that predict distal embolization during percutaneous lower extremity interventions. J Vasc Surg. 2011;53(2):347-352.
74. Heuser RR. Treatment of lower extremity vas-cular disease: the Diamondback 360 degrees Or-bital Atherectomy System. Expert Rev Med Devices. 2008;5(3):279–286.
75. Das T, Mustapha J, Indes J, et al. Technique optimiza-tion of orbital atherectomy in calcified peripheral le-sions of the lower extremities: the CONFIRM series, a prospective multicenter registry. Catheter Cardiovasc Interv. 2014;83(1):115-122.
76. Shammas NW, Lam R, Mustapha J, et al. Compari-son of orbital atherectomy plus balloon angioplasty vs. balloon angioplasty alone in patients with critical limb ischemia: results of the CALCIUM 360 randomized pilot trial. J Endovasc Ther. 2012;19(4):480-488.
77. Dattilo R, Himmelstein SI, Cuff RF. The COMPLI-ANCE 360° Trial: a randomized, prospective, mul-ticenter, pilot study comparing acute and long-term results of orbital atherectomy to balloon angioplasty for calcified femoropopliteal disease. J Invasive Cardiol. 2014;26(8):355-360.
78. Choy DS. History of lasers in medicine. Thorac Cardio-vasc Surg. 1988;36 Suppl 2:114-117.
79. Biamino G. The excimer laser: science fiction fan-tasy or practical tool? J Endovasc Ther. 2004;11 Supl 2:II207-II222.
80. Laird JR, Zeller T, Gray BH, et al.; LACI Investiga-tors. Limb salvage following laser-assisted angioplasty for critical limb ischemia: results of the LACI multi-center trial. J Endovasc Ther. 2006;13(1):1-11.
81. Dave RM, Patlola R, Kollmeyer K, et al.; CELLO In-vestigators. Excimer laser recanalization of femoropop-liteal lesions and 1-year patency: results of the CELLO registry. J Endovasc Ther. 2009;16(6):665-675.
Copyri
ght H
MP Com
munica
tions
CLINICAL REVIEW
Vascular Disease Management® October 2015 203
82. Stoner MC, deFreitas DJ, Phade SV, Parker FM, Bo-gey WM, Powell S. Mid-term results with laser ather-ectomy in the treatment of infrainguinal occlusive disease. J Vasc Surg. 2007 Aug;46(2):289-295.
83. Ambler GK, Radwan R, Hayes PD, Twine CP. Ather-ectomy for peripheral arterial disease. Cochrane Database Syst Rev. 2014;3:CD006680.
84. Banerjee S, Das TS, Abu-Fadel MS, et al. Pilot trial of cryoplasty or conventional balloon post-dilation of nitinol stents for revascularization of peripheral arte-rial segments: the COBRA trial. J Am Coll Cardiol.
2012;60(15):1352-1359.85. Andras A, Hansrani M, Stewart M, Stansby G.
Intravascular brachytherapy for peripheral vascular dis-ease. Cochrane Database Syst Rev. 2014;1:CD003504.
86. Pietzsch JB, Geisler BP, Garner AM, Zeller T, Jaff MR. Economic analysis of endovascular interventions for femoropopliteal arterial disease: a systematic review and budget impact model for the United States and Germany. Catheter Cardiovasc Interv. 2014;84(4):546-554.
Copyri
ght H
MP Com
munica
tions