608610

research-article2015
JETXXX10.1177/1526602815608610Journal of Endovascular TherapyRastan et al

Clinical Investigation

Journal of Endovascular Therapy

One-Year Outcomes Following Directional

2015, Vol. 22(6) 839­–846
© The Author(s) 2015
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DOI: 10.1177/1526602815608610

Lesions: Subgroup Results of the www.jevt.org

Prospective, Multicenter DEFINITIVE LE

Trial

Aljoscha Rastan, MD1, James F. McKinsey, MD2, Lawrence A. Garcia, MD3,

Krishna J. Rocha-Singh, MD4, Michael R. Jaff, DO5, Elias Noory, MD1,
and Thomas Zeller, MD1, on behalf of the DEFINITIVE LE Investigators

Abstract
Purpose: To report a subgroup analysis of the prospective, multicenter, single-arm DEFINITIVE LE trial to assess the
effectiveness of directional atherectomy for the treatment of infrapopliteal artery lesions at 1 year. Methods: In the
DEFINITIVE LE trial, follow-up assessments occurred up to 1 year postprocedure. Of the 800 patients enrolled, 145
subjects with 189 infrapopliteal lesions met the criteria for this analysis. Seventy (48.3%) and 75 (51.7%) patients were
suffering critical limb ischemia (CLI) and intermittent claudication, respectively; 68.3% (99/145) had diabetes. The mean
lesion length was 58±44 mm (all lesions); 20.2% were occluded. The primary endpoint for patients with claudication
was duplex ultrasound–derived primary patency, while for subjects with CLI it was freedom from major amputation
of the target limb at 1 year. Endpoints and adverse events were independently assessed. Results: Procedure success
(≤30% residual stenosis) was achieved in 84% of treated lesions. The 1-year primary patency rate was 84% (claudicants
89.6% and CLI patients 78%, p=0.11), and the freedom from major amputation rate was 97.1% (claudicants 100% and
CLI 93.8%, p=0.03). In both claudication and CLI patients, significant improvements in Rutherford category and objective
measures of walking distance and quality of life were seen at 1 year in comparison to baseline. Conclusion: This study
demonstrates that directional atherectomy in infrapopliteal arteries results in promising technical and clinical results at 1
year for claudicant as well as CLI patients.

Keywords
angioplasty, atherectomy, claudication, critical limb ischemia, infrapopliteal arteries, peripheral artery disease, tibial artery,
peroneal artery, patency, restenosis

Introduction 1
Kardiologie und Angiologie II, Universitäts-Herzzentrum Freiburg–Bad
The prevalence of peripheral artery disease (PAD) has been Krozingen, Bad Krozingen, Germany
2
Division of Vascular Surgery, New York Presbyterian Hospital,
progressively rising in developing countries. Moreover,
University Hospital of Columbia and Cornell, New York,
because of the pandemic of diabetes mellitus, the treatment NY, USA
of infrapopliteal PAD in patients with intermittent claudica- 3
Sections of Interventional Cardiology and Vascular Medicine, St.
tion and critical limb ischemia (CLI) has become more Elizabeth’s Medical Center, Tufts University School of Medicine,
prominent in daily endovascular practices.1 Boston, MA, USA
4
The Prairie Heart Institute at St. John’s Hospital, Springfield, IL, USA
In focal infrapopliteal lesions, percutaneous translumi- 5
The Institute for Heart, Vascular and Stroke Care, Massachusetts
nal angioplasty (PTA) and bare metal stent (BMS) place- General Hospital, Boston, MA, USA
ment are limited by low primary patency rates of 41% to
Corresponding Author:
58% at 1 year.2,3 In contrast, evidence shows that drug-elut-
Aljoscha Rastan, Abteilung Kardiologie und Angiologie II, Universitäts-
ing stents (DES) significantly improve patency rates to Herzzentrum Freiburg–Bad Krozingen, Südring 15, D-79189 Bad
>80% at 1 year and clinical outcomes overall in long-term Krozingen, Germany.
follow-up in comparison to PTA and BMS.4–6 Email: aljoscha.rastan@universitaets-herzzentrum.de
840 Journal of Endovascular Therapy 22(6)

However, limited data are available concerning the best Subgroup Patient Sample
treatment modality for long diffuse infrapopliteal lesions.
Midterm results in this challenging patient cohort with sig- This subgroup analysis included 145 patients (mean age
nificant comorbidities, including renal insufficiency and 73.1±10.4 years; 85 men) with 189 infrapopliteal lesions
diabetes, are disappointing, demonstrating 1-year patency from among the 800 subjects enrolled in the DEFINITIVE
rates of 31% after PTA and 70% after drug-eluting balloon LE study. The sample included 75 (51.7%) patients with
angioplasty.7 intermittent claudication and 70 (48.3%) patients with CLI.
Percutaneous removal of atherosclerotic material Characteristics of the subgroups are given in Table 1. The
through directional atherectomy represents a potential strat- most common comorbid conditions were hypertension
egy for reducing restenosis rates. A single-center registry (91%), hyperlipidemia (82.8%), and diabetes mellitus
with a limited number of patients reported high primary (68.3%). The majority of the claudicant patients were clas-
success rates and acceptable long-term results for the treat- sified as Rutherford category 3 (58, 77.3%), whereas 46
ment of infrapopliteal lesions.8 However, data from larger, (65.7%) of the patients with CLI had ischemic ulceration
prospective, independently assessed trials is lacking. (Rutherford 5 or 6). Overall, the mean lesion length was 5.8
The 1-year outcomes following directional atherectomy cm, with the majority of lesions (60.3%) ≥4 cm and 14.8%
treatment of infrapopliteal artery lesions are presented as a of lesions ≥10 cm.
subgroup analysis of the prospective, multicenter, single- The CLI cohort included significantly more diabetics
arm DEFINITIVE LE trial.9 than the claudicant cohort (78.6% vs 58.7%, p=0.012); CLI
patients also had significantly more occlusions (33.3% vs
6.5%, p<0.001) and calcified lesions (31.3% vs 13.0%,
Methods p=0.002) than claudicants, in whom de novo lesions were
more common (97.8% vs 86.5%, p=0.005; Table 2). One
Study Design
subject had missing data due to the angiogram not being
DEFINITIVE LE [Determination of EFfectiveness of the analyzable by the core laboratory.
SilverHawk PerIpheral Plaque ExcisioN System (SIlverHawk
Device) for the Treatment of Infrainguinal VEssels/Lower
Extremities] was a prospective, multicenter, single-arm study
Device Description
conducted at 47 medical centers in the United States and The study device consisted of the SilverHawk/TurboHawk
Europe in accordance with the principles of the Declaration atherectomy catheters and the cutter driver (Covidien,
of Helsinki. The study protocol was approved by the ethics Plymouth, MN, USA), all intended for single use only. The
committee at each participating institution, and each patient atherectomy catheter consists of a flexible shaft designed to
provided written informed consent. A Clinical Events track over a 0.014-inch guidewire. At the distal end of the
Committee (CEC) adjudicated major adverse events, and device is a small cutting assembly comprised of a rotating
core laboratories provided independent analyses for all inner blade contained within a tubular housing. The proxi-
scheduled and unscheduled duplex ultrasounds (VasCore, mal end of the catheter contains a connector and positioning
Massachusetts General Hospital, Boston, MA, USA) and lever designed to fit into a small, disposable, battery-driven
angiographic data (SynvaCor, Springfield, IL, USA). cutter driver, which powers the device. The SilverHawk and
Patients were eligible for the study if they were at least TurboHawk atherectomy catheters were cleared for com-
18 years old and suffered from PAD (Rutherford category mercial use by the Food and Drug Administration and the
1–6). Angiographic eligibility for the infrapopliteal subco- European Union.
hort required the presence of a de novo or restenotic target
lesion (occlusion or stenosis) in the infrapopliteal arteries
(reference vessel diameter 1.5–7 mm) with a stenosis of at
Study Procedures
least 50%, estimated by angiography. Major exclusion cri- Study procedures were previously described in detail.9
teria were the presence of severe calcification in the target Significant stenosis of inflow arteries had to be treated suc-
lesion (defined as radiopacities noted on both sides of the cessfully prior to enrollment. In lesions where the atherec-
arterial wall and extending >1 cm in length prior to contrast tomy catheter was unable to cross, predilation was
injection or digital subtraction angiography), in-stent reste- permitted. The selection of the atherectomy device model
nosis, previous peripheral artery bypass graft surgery affect- and the number of infrapopliteal lesions treated with direc-
ing the target limb, previous amputation above the tional atherectomy was left to the discretion of the treating
metatarsal level of the target limb, known systemic coagu- physician.
lopathy, renal failure requiring dialysis, life expectancy <12 In the event of major flow-limiting dissection, perfora-
months or other factors making follow-up impossible, and/ tions, occlusive complications (ie, recoil), or residual stenosis
or intolerance to aspirin, clopidogrel, or heparin. >30% of the target lesion following directional atherectomy,
Rastan et al 841

Table 1.  Baseline Patient Demographics.

Patient Characteristics Total (n=145)a Claudicants (n=75)a CLI (n=70)a p

Age, y 73.1±10.4 72.0±10.9 74.3±9.8 0.174
Men 85 (58.6) 46 (61.3) 39 (55.7) 0.505
History/risk factors
 Diabetes 99 (68.3) 44 (58.7) 55 (78.6) 0.012
 Arrhythmia 22 (15.2) 6 (8.0) 16 (22.9) 0.019
  Congestive heart failure 25 (17.2) 11 (14.7) 14 (20.0) 0.510
  Coronary artery disease 53 (36.6) 29 (38.7) 24 (34.3) 0.608
 Stroke 23 (15.9) 11 (14.7) 12 (17.1) 0.820
  Myocardial infarction 29 (20.0) 17 (22.7) 12 (17.1) 0.533
  CABG or PCI 53 (36.6) 31 (41.3) 22 (31.4) 0.231
 Hypertension 132 (91.0) 68 (90.7) 64 91.4) 1.000
 Hyperlipidemia 120 (82.8) 65 (86.7) 55 (78.6) 0.271
  Renal insufficiency 32 (22.1) 13 (17.3) 19 (27.1) 0.166
  Nonhealing ischemic ulcers 46 (31.7) 2 (2.7) 44 (62.9) <0.001
  Tobacco use—current 19 (13.1) 12 (16.0) 7 (10.0) 0.331
Rutherford category
 1 3 (2.1) 3 (4.0) 0 (0.0)  
 2 14 (9.7) 14 (18.7) 0 (0.0)  
 3 58 (40.0) 58 (77.3) 0 (0.0)  
 4 24 (16.6) 0 (0.0) 24 (34.3)  
 5 44 (30.3) 0 (0.0) 44 (62.9)  
 6 2 (1.4) 0 (0.0) 2 (2.9)  

Abbreviations: CABG, coronary artery bypass graft; CLI, critical limb ischemia; PCI, percutaneous coronary intervention.
a
Continuous data are presented as the means ± standard deviation; categorical data are given as the counts (percentage).

Table 2.  Lesion Characteristics.

Lesion Characteristics Total (n=189)a Claudicants (n=93)a CLI (n=96)a p

Target artery
  Anterior tibial 67/189 (35.4) 28/93 (30.1) 39/96 (40.6) 0.170
 Peroneal 36/189 (19.0) 14/93 (15.1) 22/96 (22.9) 0.196
  Posterior tibial 35/189 (18.5) 18/93 (19.4) 17/96 (17.7) 0.852
  Tibioperoneal trunk 51/189 (27.0) 33/93 (35.5) 18/96 (18.8) 0.013
Lesion length, cm 5.8±4.4 (189) 5.5±4.1 (93) 6.0±4.6 (96) 0.464
Baseline stenosis, %b 74.5±18.4 (188) 72.0±15.7 (92) 76.8±20.5 (96) 0.073
Occlusionsb 38/188 (20.2) 6/92 (6.5) 32/96 (33.3) <0.001
Calcificationb
 None 146/188 (77.7) 80/92 (87.0) 66/96 (68.8) 0.002
 Present 42/188 (22.3) 12/92 (13.0) 30/96 (31.3) 0.002
De novo (site assessed) 174/189 (92.1) 91/93 (97.8) 83/96 (86.5) 0.005
Target lesion length, cm
  ≥10.0 28/189 (14.8) 12/93 (12.9) 16/96 (16.7) 0.541
 4.0–9.9 86/189 (45.5) 47/93 (50.5) 39/96 (40.6) 0.190
 <4 75/189 (39.7) 34/93 (36.6) 41/96 (42.7) 0.457
TASC 0.042
 A 129/188 (68.6) 70/92 (76.1) 59/96 (61.5)  
 B 48/188 (25.5) 18/92 (19.6) 30/96 (31.3)  
 C/D 11/188 (5.9) 4/92 (4.3) 7/96 (7.3)  

Abbreviations: CLI, critical limb ischemia; TASC, TransAtlantic Inter-Society Consensus.

a
Continuous data are presented as the means ± standard deviation (sample size if less than n); categorical data are given as the count/sample (percentage).
b
Some data points are missing as the quality of the captured procedural images was not analyzable by the core laboratory.
842 Journal of Endovascular Therapy 22(6)

adjunctive endovascular procedures were allowed. Distal the index procedure. All major adverse events were adjudi-
protection devices, permitted under the study protocol, were cated by an independent CEC.
used at the discretion of the attending physician.
It was recommended that all subjects receive antiplatelet or
Statistical Analysis
antithrombotic therapy pre- and postprocedure per American
Heart Association/American College of Cardiology/European Continuous data are presented as the means ± standard
Society of Cardiology guidelines.1 deviation [n] or median [interquartile range (IQR): 25th to
75th percentile]. Categorical variables are expressed as
counts and percentage. Statistical comparisons were per-
Baseline and Follow-up Evaluations formed using the Fisher exact test for categorical variables
Before the procedure and during follow-up visits after 3, 6, and the Student t test for continuous variables. Changes in
and 12 months, all patients had clinical examination, mea- Rutherford category were expressed as the median with
surement of the ankle-brachial index (ABI), Rutherford cat- IQR, and comparisons were evaluated using the Wilcoxon
egory classification, target lesion evaluation by duplex, signed-rank test. Event-free rates were calculated by
quality of life measurements [EuroQOL 5 Domains (EQ- Kaplan-Meier analysis with comparisons using the Mantel-
5D) and Walking Impairment Questionnaire (WIQ) in Cox log-rank test. The Kaplan-Meier survival analyses for
patients with Rutherford category 1–3 at baseline], wound patency and freedom from clinically driven TLR were
assessment (in patients with Rutherford category 5 or 6 at based on the time to the first event for each target lesion,
baseline), and adverse event evaluation. while survival analysis of freedom from MAE was based on
the first event for each patient. P values were 2-sided, with
values <0.05 deemed statistically significant. All statistical
Endpoints analyses were performed using SAS for Windows (version
Primary patency after 1 year was defined as freedom from 9.1 or higher; SAS Institute Inc, Cary, NC, USA).
target lesion restenosis detected with duplex ultrasound and To investigate the effect of covariates, multivariate logis-
no reintervention. The definition of a restenosis detected by tic regression analysis was conducted for procedure success
duplex was based on the peak systolic velocity ratio and multivariate Cox regression for primary patency. The
(PSVR), which was calculated as the peak systolic velocity significance level for entry of independent variables from
within the target lesion divided by the peak systolic velocity the univariate model into the multivariate model was 0.1.
proximal of the target lesion in a healthy vessel segment. The explanatory covariates included gender, age, diabetes,
The primary study endpoint was defined by PSVR ≥3.5; a arrhythmia, hypertension, hyperlipidemia, renal insuffi-
PSVR ≥2.4 was used as a secondary endpoint. Patency rates ciency, smoking within last 10 years, claudication vs CLI
are reported based on the PSVR ≥2.4 value, as this has been status, lesion length, occluded vs stenotic lesions, reference
clinically established to represent >50% restenosis.10 For vessel diameter, calcification, and TransAtlantic Inter-
subjects with claudication (Rutherford category 1–3) at Society Consensus (TASC) classification.
baseline, the primary endpoint was primary patency; for
patients with CLI (Rutherford category 4–6) at baseline, the
primary endpoint was defined as freedom from major, Results
unplanned amputation of the target limb at 1 year.
Acute Outcomes
Secondary endpoints included device success (defined
as ≤30% residual stenosis following directional atherec- The majority of subjects (87.6%) were treated with
tomy without adjunctive endovascular interventions as SilverHawk devices only, whereas 15 (10.3%) subjects with
assessed by the angiographic core laboratory); secondary multiple lesions were treated with both SilverHawk and
patency [defined as patency at 1 year following successful TurboHawk devices. Two (1.4%) subjects received treat-
target lesion revascularization (TLR)]; changes in ABI, ment with TurboHawk devices only (the device used for
Rutherford category, and the EQ-5D Questionnaire; and one subject was not specified). Predilation of the target
limb salvage at 1 year for the entire cohort. Changes in the lesion was performed in 9 (9.7%) subjects treated for clau-
WIQ scores were assessed for the claudicant cohort only. dication and 13 (13.5%) of those in CLI subjects (p=0.50).
For the CLI cohort, additional secondary endpoints were Device success (≤30% residual stenosis following direc-
primary patency at 1 year and wound healing at 3 months tional atherectomy) was achieved in 69.6% of all lesions
(defined as a decrease of at least one Wagner class grade). and did not differ significantly between the claudicant and
Death, major unplanned amputation of the target limb, CLI cohorts (72.7% vs 66.7%, p=0.42; Table 3). Device
and clinically driven target vessel revascularization (TVR) success was 69.8% (113/162) for lesions treated with
were defined as major adverse events (MAEs). All major SilverHawk only and 75.0% for lesions treated with both
events were determined cumulatively for the 365 days after SilverHawk and TurboHawk (p=0.78).
Rastan et al 843

Table 3.  Procedure Data.

Procedure Characteristics Totala (n=145) Claudicantsa (n=75) CLIa (n=70) p

Procedure time, min 77.8±32 75.8±30 79.9±34 0.452
Fluoroscopy time, minb 20.1±10 (144) 19.3±9 20.9±11 (69) 0.351
Contrast, mLb 164.3±91 (144) 176.2±97 (75) 151.3±82 (69) 0.098
Use of embolic protection (SpiderFX only) 27/145 (18.6) 12/75 (16.0) 15/70 (21.4) 0.522
Outcomes per lesion n=189 n=93 n=96  
  Device successb,c 126/181 (69.6) 64/88 (72.7) 62/93 (66.7) 0.420
  Postdevice stenosis, %b,c 26.9±14 (181) 25.7±14 (88) 28.0±15 (93) 0.301
  Procedure successb,c 157/187 (84.0) 78/91 (85.7) 79/96 (82.3) 0.555
  Postprocedure stenosis, %b,c 22.2±11 (187) 20.9±10 (91) 23.4±12 (96) 0.116
a
Continuous data are presented as the means ± standard deviation (sample size if less than n); categorical data are given as the count/sample
(percentage).
b
Missing data were either not reported by the site or not analyzable by the core laboratory.
c
As assessed by the core laboratory.

Table 4.  Periprocedural Events Within 30 Days.

Eventa Total (n=145) Claudicants (n=75) CLI (n=70) p

Patients with at least 1 event 16 (11.0) 11 (14.7) 5 (7.1) 0.188
Distal embolization 4 (2.8) 1 (1.3) 3 (4.3) 0.353
  Intervention: PTA 3 1 2  
Abrupt closure 3 (2.1) 1 (1.3) 2 (2.9) 0.609
  Intervention: surgery 1 0 1  
Dissection (flow-limiting) 4 (2.8) 4 (5.3) 0 0.120
  Intervention: PTA/stent 1/1 1/1 —  
Perforation 8 (5.5) 7 (9.3) 1 (1.4) 0.064
Intervention required: PTA 6 5 1  

Abbreviation: PTA, percutaneous transluminal angioplasty.

a
Includes events occurring from the index procedure to 30 days postprocedure; rates are presented per patient; patients may have more than one
event type and appear in multiple rows, thus the sum of the rows need not sum to the overall event rate.

After atherectomy, adjunctive therapy was performed in arterial perforation, 6 (4.1%) patients had additional PTA of
37% of the target lesions, with the majority receiving post- the target lesion. Abrupt closure occurred in 3 (2.1%)
dilation (66, 34.9%). For 37 of the 66 lesions with adjunc- patients, distal embolization in 4 (2.8%), and flow-limiting
tive PTA, the residual stenosis post atherectomy was ≥30%. dissections in 4 (2.8%) subjects. All events were adjudi-
The adjunctive stent rate was 1.6% (n=3). No drug-eluting cated by the CEC and reviewed by the angiographic core
balloons or stents were used for adjunctive therapy. laboratory.
Procedure success (≤30% residual stenosis at the end of the
procedure) was achieved in 84% of target lesions (85.7%
Follow-up Outcomes
for the claudicants vs 82.3% for the CLI group, p=0.56;
Table 3). Multivariate analysis revealed target lesion occlu- Follow-up compliance was 77.9% at 6 months and 71.7% at
sion (vs stenosis, p=0.004) and hyperlipidemia (p=0.045) as 12 months. Patient disposition through 1 year included 104
predictors of procedure success. study completions, 28 (19.3%) withdrawals from the study,
A total of 39 inflow lesions that did not meet the protocol 7 (4.8%) lost to follow-up, and 6 (4.1%) deaths (Figure 1).
requirements for inclusion as target lesions were treated Study completion was achieved for 59 (78.7%) claudicants
during the index procedure; 16 were treated prior to and 23 and 45 (64.3%) CLI patients.
following the treatment of the target lesions. The majority At 1 year, duplex-documented primary patency was
(27, 69.2%) of treated inflow lesions were in the superficial 84%, with no significant differences between the claudicant
femoral artery, followed by the popliteal (6, 15.4%), iliac and CLI cohorts (p=0.11; Figure 2A). Secondary patency at
(5, 12.8%), and common femoral (1, 2.6%) arteries. 1 year was 92.1%. Freedom from clinically-driven TLR at 1
Adverse events through 30 days were noted in 16 year was 91.2% overall, with 95.4% for claudicants and
(11.0%) patients (Table 4). Of the 8 (5.5%) patients with an 86.6% for CLI (p=0.09; Figure 2B). Multivariate Cox
844 Journal of Endovascular Therapy 22(6)

Figure 1.  Study profile.

regression analysis revealed patient age (p=0.014), history

of arrhythmia (p=0.032), and renal insufficiency (p=0.019)
as independent predictors of restenosis.
The median Rutherford category decreased from 3 at
baseline to 2 at 6 months (p<0.001) and to 1 at 1 year
(p<0.001), with significant improvements seen in median
change from baseline for both the claudicant (–2.0) and CLI
(–1.0) cohorts (Table 5). For ABI, the change post procedure
was evaluated only for subjects who had a baseline ABI <0.9
and an improvement was evaluable (47 subjects were
excluded with an ABI ≥0.9 at baseline). Additional subjects
Figure 2.  (A) Primary patency per lesion. (B) Freedom from
had missing ABIs at baseline (n=21), 6 months (n=16), and target lesion revascularization (TLR) per lesion. (C) Freedom
12 months (n=20) and were not included in the change anal- from major adverse events (MAEs) per patient. The standard
yses. Mean ABI improved from 0.67 at baseline to 0.80 at 6 error did not exceed 10% at any time point in any graph. CLI,
months (p<0.001) and to 0.84 at 1 year (p<0.001). Mean critical limb ischemia.
increases in ABI at 1 year were similar for the claudicant and
CLI cohorts (0.15±0.16 vs 0.16±0.44, p=0.83). observed in 68.2% of patients (30/44) with a baseline
Quality of life, as measured by the EQ-5D visual analog Rutherford category of 5 or 6.
score, significantly increased from a mean of 65.1±18.2 at
baseline to 71.8±18.5 at 1 year (p=0.004). Similarly, a sig-
nificant improvement in walking distance, as measured by Complications
the WIQ in claudicants only, was seen with a mean score of Overall, the Kaplan-Meier freedom from MAE estimate
22.4±27.1 at baseline increasing to 41.2±36.3 at 1 year was 79.6% at 1 year, with 86% for the claudicant cohort and
(p<0.001). For the CLI cohort, wound healing at 1 year was 72.6% for the CLI cohort (p=0.03; Figure 2C). In total, 6
Rastan et al 845

Table 5.  Functional Outcomes.

Overalla Claudicantsa CLIa

Functional
Assessment  Baseline 1 Year Baseline 1 Year Baseline 1 Year
Rutherford 3.0 (3.0, 5.0) 1.0 (1.0, 3.0) 3.0 (3.0, 3.0) 1.0 (1.0, 2.0) 5.0 (4.0, 5.0) 3.0 (1.0, 5.0)
category [145] [104] [75] [59] [70] [45]
12-month change –2.0 (–2.0, 0.0) –2.0 (–2.0, –1.0) –1.0 (–3.0, 0.0)
from baseline p<0.001 p<0.001 p<0.001
Ankle-brachial 0.67±0.15 0.84±0.25 [57] 0.70±0.12 0.86±0.16 [34] 0.64±0.19 0.80±0.34 [23]
index [77] [44] [33]
12-month change 0.15±0.30 [57] 0.15±0.16 [34] 0.16±0.44 [23]
from baseline p<0.001 p<0.001 p=0.102

Abbreviation: CLI, critical limb ischemia.

a
Continuous data are presented as the means ± standard deviation [n] or median (25th, 75th percentile) [n].

deaths, 4 unplanned major amputations, and 30 clinically- months. The mean infrapopliteal lesion length was 33.4±47.2
driven TVRs occurred. The deaths were due to myocardial mm. Procedure success (defined as ≤50% final residual ste-
infarction (n=3), cardiogenic shock, stroke, and cerebral nosis) was achieved in 97.6% of patients. At 6 and 12
hemorrhage. None of the deaths was adjudicated by the months, 90% and 80% of all lesions were free from TLR,
CEC as related to either the study device or the index proce- respectively. However, beside the study design (retrospec-
dure. Five of the 6 deaths occurred in the CLI cohort, for tive registry), the results of TALON were impacted by other
1-year survival estimates of 98.6% for the claudicant cohort, limitations. First, the results presented were site-reported;
95.4% for the CLI cohort, and 97.1% overall. All major there was neither core laboratory analysis nor a CEC incor-
amputations occurred in the CLI cohort for 1-year limb sal- porated. Second and most important is the considerably high
vage estimates of 100% for the claudicant cohort, 93.8% for number of patients (514, 85%) lost to follow-up. However,
the CLI cohort (p=0.03), and 97.1% overall. DEFINITIVE LE, which addressed these limitations,
achieved similar freedom from TLR rates as reported in
TALON.
Discussion
Additionally, Kandzari et al12 reported a series of 69
This is the largest modern prospective series describing the patients with CLI involving 76 limbs that were treated
efficacy and midterm outcomes of directional atherectomy with directional atherectomy. The primary endpoint was
in infrapopliteal arteries. All outcomes were determined by major adverse events (death, myocardial infarction,
independent core laboratories and adverse events were unplanned amputation, or repeat TVR) at 30 days, which
adjudicated by an independent CEC. occurred in 1% of patients. Amputation was avoided in
The results of this subgroup analysis revealed promis- 82% of patients at 6 months. Another report of longer
ing technical and clinical outcomes for directional ather- follow-up after infrapopliteal revascularization with
ectomy in the treatment of infrapopliteal arteries for both directional atherectomy included 36 patients with 49
claudicant and CLI patients. In addition to secondary lesions.8 The mean target lesion length was 48±28 mm.
patency and freedom from TLR rates in excess of 90% at Primary patency was 60% at 2 years, and there were no
1 year, directional atherectomy resulted in significant major amputations.
improvements in ABI, Rutherford category, and quality There is evidence that DES are superior to PTA and
of life (WIQ and EQ-5D). Moreover, there were no sig- BMS in terms of primary patency and clinical improve-
nificant differences between the patients with claudica- ment after treating focal (<4 cm) infrapopliteal lesions.4,6
tion vs CLI concerning the patency rates at 6 and 12 In the YUKON-BTK randomized double-blind study, DES
months after the index procedure. However, as expected, achieved significantly higher primary patency rates
the incidence of major adverse events was significantly (80.6%) as compared with BMS (55.6%, p=0.004) at 1
higher in patients with CLI. year, whereas the ACHILLES trial underlined the advan-
Prior to the DEFINITIVE LE study, the largest direc- tage of DES over PTA (77.6% vs 58.1%, p=0.019 for pri-
tional atherectomy study published was the TALON mary patency). Moreover, in both trials the improvement in
Registry.11 This retrospective uncontrolled registry involved Rutherford category was significantly more pronounced in
19 centers in the United States and enrolled 601 patients patients treated with DES.4,6
with symptomatic femoropopliteal and infrapopliteal artery In diffuse (>10 cm) infrapopliteal lesions, drug-coated
lesions. The primary endpoint of the study was TLR at 12 balloon (DCB) angioplasty is likely the most promising
846 Journal of Endovascular Therapy 22(6)

treatment modality, providing significantly higher primary References

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Conclusion eral intervention for below the knee angioplasty evaluation
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Declaration of Conflicting Interests of duplex ultrasound quantification of peripheral arte-
rial stenoses. Studies of the cardiovascular model and in
The author(s) declared no potential conflicts of interest with
angiography patients [in German]. Med Klin (Munich).
respect to the research, authorship, and/or publication of this
1995;90:72–77.
article.
11. Ramaiah V, Gammon R, Kiesz S, et al. Midterm outcomes from
the TALON registry: treating peripherals with SilverHawk:
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The author(s) report receiving the following financial support for 12. Kandzari DE, Kiesz RS, Allie D, et al. Procedural and clinical
the research, authorship, and/or publication of this article: This outcomes with catheter-based plaque excision in critical limb
work was supported by Covidien. ischemia. J Endovasc Ther. 2006;13:12–22.