Treating Post-Angioplasty Dissection in the Femoropopliteal Arteries Using the Tack Endovascular System

JACC: CARDIOVASCULAR INTERVENTIONS

VOL. 12, NO. 23, 2019

ª 2019 THE AUTHORS. PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION. THIS IS AN OPEN ACCESS ARTICLE UNDER THE CC BY-NC-ND LICENSE (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Treating Post-Angioplasty Dissection in the Femoropopliteal Arteries Using the Tack Endovascular System 12-Month Results From the TOBA II Study William A. Gray, MD,a Joseph A. Cardenas, MD,b Marianne Brodmann, MD,c Martin Werner, MD,d Nelson I. Bernardo, MD,e Jon C. George, MD,f Alexandra Lansky, MDg

ABSTRACT OBJECTIVES The aim of this study was to evaluate the Tack Endovascular System (Intact Vascular, Wayne, Pennsylvania) for treating dissections following angioplasty in the superficial femoral artery and/or proximal popliteal artery. BACKGROUND Dissection after angioplasty of femoropopliteal arteries with either a plain balloon or a drug-coated balloon (DCB) can negatively affect both short- and long-term outcomes. METHODS TOBA (Tack Optimized Balloon Angioplasty) II is a prospective, single-arm, multicenter study enrolling 213 patients, all with dissection following angioplasty. Eligibility included Rutherford classification 2 to 4 with a de novo or nonstented restenotic lesion in the superficial femoral artery or proximal popliteal artery undergoing plain balloon or DCB angioplasty. Following dilation, lesions with <30% residual stenosis and presence of $1 dissection were enrolled. The 12month efficacy endpoint was primary patency (freedom from duplex-derived binary restenosis and clinically driven target lesion revascularization. RESULTS Patients’ mean age was 68
9 years, and 43.2% had diabetes. Twenty-three percent of lesions were chronic total occlusions, and w60% had moderate to severe calcium. The mean lesion length was 74.3
40.6 mm. Severe dissection (grade $C) was present in 69.4%. By operator choice, 57.7% of patients underwent DCB angioplasty. Most (92.1%) dissections resolved completely, and only 1 bailout stent was required. There were no 30-day major adverse events. The 12-month efficacy endpoint was met, with Kaplan-Meier primary patency and freedom from clinically driven target lesion revascularization of 79.3% and 86.5%, respectively. At 12 months, there were no device fractures or clinically significant migrations, and significant improvements were noted in Rutherford category, ankle-brachial index, and quality of life. CONCLUSIONS TOBA II demonstrated the safety and efficacy of the Tack Endovascular System for focal dissection repair following standard and DCB angioplasty. (J Am Coll Cardiol Intv 2019;12:2375–84) © 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

P

eripheral artery disease (PAD) is a chronic

as a “pandemic,” lower extremity PAD is estimated to

occlusive disease characterized by obstructive

affect 202 million people globally, 20 million people

plaque that can result in claudication and crit-

in the United States, and up to 20% of Americans

ical limb ischemia (1). Described by Hirsch and Duval (2)

> 75 years of age (3,4). Revascularization, particularly

From the aLankenau Heart Institute, Wynnewood, Pennsylvania; bYuma Cardiology Associates, Yuma Regional Medical Center, Yuma, Arizona; cDivision of Angiology, Medical University Graz, Graz, Austria; dDepartment of Angiology, Hanusch Hospital, Vienna, Austria; eMedStar Washington Hospital Center, Washington, District of Columbia; fEinstein Medical Center, Philadelphia, Pennsylvania; and gYale Cardiovascular Research Group, New Haven, Connecticut. This study was funded by Intact Vascular. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received April 11, 2019; revised manuscript received July 29, 2019, accepted August 6, 2019.

ISSN 1936-8798

https://doi.org/10.1016/j.jcin.2019.08.005

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JACC: CARDIOVASCULAR INTERVENTIONS VOL. 12, NO. 23, 2019 DECEMBER 9, 2019:2375–84

TOBA II 12-Month Results

ABBREVIATIONS

minimally invasive endovascular therapy,

limiting the amount of biological injury. We report

AND ACRONYMS

remains the treatment of choice for most

the results of the TOBA (Tack Optimized Balloon

patients

limb-

Angioplasty) II study evaluating the Tack Endovas-

threatening PAD despite optimal medical ther-

cular System in treating post-angioplasty dissections

apy (5,6). The recurrent nature of the disease

in the SFA and/or proximal popliteal artery (PPA).

DCB = drug-coated balloon DUS = duplex ultrasound MAE = major adverse event PAD = peripheral artery disease

POBA = plain balloon

with

life-style-limiting

or

following intervention is associated with higher

METHODS

health care–related expenditures (7). Most endovascular therapeutic approaches to PAD involve percutaneous transluminal

DESIGN AND STUDY POPULATION. TOBA II was a

angioplasty (PTA) as definitive or adjunctive

prospective, single-arm, multicenter study conducted

therapy. Balloon angioplasty functions by

at clinical centers in the United States and Europe.

both mechanically stretching the atheroscle-

This was an investigational device exemption study

transluminal angioplasty

rotic artery and inducing dissection, result-

conducted in compliance with the International

RC = Rutherford category

ing in acute vascular injury (8). Angiographic

Conference on Harmonization Good Clinical Practice,

SFA = superficial femoral

evidence of dissections is frequent, reported

ISO 14155, and the Declaration of Helsinki. The local ethics

artery

in up to 84% of femoropopliteal angioplasties

committees at the participating sites approved the study

TLR = target lesion

(9).

or

protocol, and all patients provided written informed

revascularization

obstruct flow, requiring additional thera-

consent before undergoing any study procedures. This

angioplasty

PPA = proximal popliteal artery

PTA = percutaneous

Acutely,

dissection

can

reduce

peutic intervention, and over the long-term, lesions

study is registered at ClinicalTrials.gov (NCT02522884).

with dissections have 3.5 times the rate of repeat

The objectives of the study were to evaluate the

target lesion revascularization (TLR) than lesions

safety and efficacy of the Tack Endovascular System

without (10–12). Because dissections can negatively

for the repair of all dissections types (A to F). The

affect procedural and clinical outcomes, most angio-

study allowed the use of plain balloon angioplasty

plasty trials exclude patients with moderate to severe

(POBA) or Lutonix drug-coated balloons (DCBs) for

dissection (13–16) as a potential confounder.

treatment of patients with PAD of the SFA or PPA.

SEE PAGE 2385

Dissections are mostly treated with stent placement. By scaffolding the vessel wall with high radial outward force, stents treat the dissection but can

Balloon choice was at the discretion of the operator. Training in dissection identification and the use of the study device was provided to each operator prior to the index procedure. Eligible participants were $18 years of age with

present additional challenges, especially with longer

Rutherford

lesions. Stents have been shown to improve proce-

Angiographic

category

dural outcomes, but beyond the acute treatment

atherosclerotic lesions ($70% diameter stenosis) in

phase, the aggressive radial force combined with an

the SFA, PPA, or both that met the clinical in-

extensive amount of nitinol can cause inflammation

dications for treatment. Specific lesion length in-

and lead to intimal hyperplasia formation, in-stent

clusion criteria were $20 and #150 mm for lesions

restenosis, and high rates (20% to 37%) of restenosis

with 70% to 99% stenosis and #100 mm for arteries

1 year post-treatment (17–20). The dynamic forces

that were occluded, respectively. Reference vessel

exerted in the femoropopliteal segment can lead to

diameter was required to be between 2.5 and

additional shear stress, inflammation, and occasional

6.0 mm, inclusive. Key exclusion criteria were pre-

stent fracture (21,22).

vious infrainguinal bypass graft in the target limb;

criteria

(RC) for

2

to

4

claudication.

enrollment

included

Given the inherent limitations of stent placement,

previously implanted stent in the target vessel;

limiting the metal footprint for dissection treatment

planned amputation of the target limb; planned non-

represents an alternative solution. The Tack Endo-

PTA treatment (other than a crossing device) of the

vascular System (Intact Vascular, Wayne, Pennsylva-

target lesion; serum creatinine >2.5 mg/dl; acute

nia) is a novel device specifically designed to address

vessel occlusion or acute or subacute thrombosis in

the limitations of stents while providing durable

the target lesion; severe calcification (defined as

repair of post-PTA dissections in the superficial

>5 cm of circumferential calcium or calcium that

femoral artery (SFA) and infrapopliteal artery. To

renders the lesion nondilatable); presence of post-

reduce the metal surface area in contact with the

dilation residual diameter stenosis $30%; and lack

luminal wall, Tack implants are short (6 mm), with an

of adequate distal runoff, defined as presence of at

open-cell design resulting in lower chronic outward

least 1 patent (<50% diameter stenosis) infrapopli-

force compared with similar-sized stents. This allows

teal vessel that had not been revascularized prior to

focal dissection treatment and scaffolding while

the index procedure.

Gray et al.

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TOBA II 12-Month Results

C ENTR AL I LL U STRA T I ON Tack Endovascular System

100

100

80

80

70

70

60 50 40

89.6%

90

85.1 ± 40.6

59.8 ± 35.8

Percent

Lesion Length (mm)

90

69.2%

69.7%

71.9%

60 50 40

30

30

20

20

10

10

0

0

33.9%

8.9%

Occlusion DCB Group

Dissection ≥ C

K-M Patency

POBA Group

Gray, W.A. et al. J Am Coll Cardiol Intv. 2019;12(23):2375–84.

The Tack Endovascular System (top) consists of 6 Nitinol implants pre-loaded on a single delivery catheter for the repair of post-angioplasty dissections. Primary patency in TOBA (Tack Optimized Balloon Angioplasty) II (bottom) shows a post hoc analysis of lesion characteristics and primary patency by balloon type. DCB ¼ drug-coated balloon; K-M ¼ Kaplan-Meier; POBA ¼ plain balloon angioplasty.

STUDY DEVICE. The Tack Endovascular System con-

A baseline angiogram was obtained prior to dilation to

sists of a 6-F (2.0-mm) delivery catheter pre-loaded

confirm baseline angiographic eligibility for inclusion

with 6 independent Nitinol implants that measure

or exclusion, including reference vessel diameter

6 mm in length (Central Illustration). The implants are

measurement. Pre-enrollment treatment was then

of a single size and self-expanding, treating a full

performed with POBA or the Lutonix DCB on the basis

range of vessel diameters from 2.5 to 6.0 mm.

of operator preference. Post-angioplasty, the target

PROCEDURE. Procedural techniques were performed

lesion was required to have <30% residual diameter

in accordance with the institutional standard of care

stenosis and presence of at least 1 dissection of any

for endovascular treatment of the femoropopliteal

National Heart, Lung, and Blood Institute grade A to F

segment, including appropriate antiplatelet therapy.

by visual estimate (23). Several angiographic views (at

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TOBA II 12-Month Results

T A B L E 1 Baseline Patient Demographic and Clinical

F I G U R E 1 Tack Optimized Balloon Angioplasty II Enrollment

Characteristics

68.2
9.1

Age, yrs

213

Male

211

151 (70.9)

Coronary artery disease

211

128 (60.7)

Congestive heart failure

211

24 (11.4)

Cerebrovascular event Transient ischemic attack Stroke: cerebrovascular accident

209

24 (11.5) 10 (4.8) 14 (6.7)

Chronic renal insufficiency

213

19 (8.9)

Diabetes mellitus Type I Type II

213

92 (43.2) 3 (1.4) 89 (41.8)

Hypertension

213

191 (89.7)

Hyperlipidemia

211

184 (87.2)

Current smoker

213

66 (31.0)

Rutherford clinical category 2 3 4

213

Ankle-brachial index in target limb

200

0.76
0.21

De novo lesions

213

202 (94.8)

Target lesion location SFA Popliteal artery: P1 segment SFA and P1

211

68 (31.9) 136 (63.8) 9 (4.2)

184 (87.2) 12 (5.7) 15 (7.1) 74.3
40.6

Target lesion length, mm

211

Proximal RVD, mm

211

5.3
0.7

Distal RVD, mm

211

5.5
0.7

Total occlusion

211

49 (23.2)

Calcification None/mild Moderate Severe

211

% pre–diameter stenosis

129

86 (40.8) 113 (53.6) 12 (5.7) 73.5
18.2

Patients were enrolled into TOBA (Tack Optimized Balloon Angioplasty) II if there was a dissection following plain balloon angioplasty (POBA) or drug-coated balloon (DCB)

Values are n, mean
SD, or n (%). RVD ¼ reference vessel diameter; SFA ¼ superficial femoral artery.

angioplasty. Balloon choice was at the discretion of the investigator.

least 2 views 45  apart) were obtained to document the dissections per angiographic protocol.

lesion, dissection grade, and angiographic outcome

ENROLLMENT. Following angiographic identification

was conducted by an independent core laboratory

of dissection(s), the delivery catheter was loaded onto

(Yale Cardiovascular Research Group Angiographic

a 0.035-inch guidewire. Once the study device was

Core Laboratory). Duplex ultrasound (DUS) was con-

inserted through the introducer sheath, the patient

ducted at 1, 6, and 12 months and analyzed by an

was considered enrolled (Figure 1). The operator

independent DUS core laboratory (VasCore, Bos-

evaluated the angiogram and deployed Tack(s) to

ton, Massachusetts).

treat the dissections accordingly, and then post-Tack

PRIMARY ENDPOINTS. The primary endpoints were

placement angioplasty was performed to seat the

compared against performance goals derived in

implant(s). Angiography was performed to verify

cooperation with the U.S. Food and Drug Adminis-

acceptable acute vessel patency.

tration. The primary safety endpoint was freedom

ANGIOGRAPHY

AND

DUPLEX

ULTRASOUND.

from any new-onset major adverse events (MAEs) at

Angiographic data for the determination of study

30 days (defined as index limb amputation above the

enrollment were obtained by the investigator at the

ankle, clinically driven [CD] TLR, or all-cause death),

time of the index procedure. Evaluation of the target

compared to the VIVA Physicians Group performance

Gray et al.

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TOBA II 12-Month Results

T A B L E 2 Procedure Outcomes

T A B L E 3 Dissection Grades

Balloon type Standard Drug-coated balloon

213

Approach Ipsilateral Contralateral

213

90 (42.3) 123 (57.7) 61 (28.6) 152 (71.4)

Dissection Type

Most severe dissection per patient None

Investigator Reported

Core Laboratory Reported

(n ¼ 213)

(n ¼ 209)

0 (0.0)

1 (0.5)

A

29 (13.6)

21 (10.0)

Residual diameter stenosis: pre-Tack

211

24.9
8.8

B

57 (26.8)

42 (20.1)

Number of dissections per patient

209

1.8
0.9

C

91 (42.7)

93 (44.5)

Number of Tacks deployed per patient

213

4.1
2.5

D

33 (15.5)

51 (24.4)

Number of Tacks used to treat each dissection

368

2.2
1.9

E

3 (1.4)

0 (0.0)

Device success

213

204 (95.8)

F

0 (0.0)

1 (0.5)

Procedure success

213

212 (99.5)

(n ¼ 417)

(n ¼ 368)

% post–diameter stenosis

208

20.5
6.5

Values are n, n (%), or mean
SD.

goal (24). The primary efficacy endpoint compared primary patency at 12 months against a performance goal based on the results of the LEVANT 2 clinical trial (13). Primary patency was defined as freedom from CD

All dissections None

0 (0.0)

1 (0.3)

A

80 (19.2)

67 (18.2)

B

144 (34.5)

130 (35.2)

C

149 (35.7)

118 (32.0)

D

41 (9.8)

52 (14.1)

E

3 (0.7)

0 (0.0)

F

0 (0.0)

1 (0.3)

Values are n (%). Dissection grades were reported both for all dissections and for the most severe dissection for each patient.

TLR and freedom from DUS-derived binary restenosis at 12 months (defined as peak systolic velocity ratio $2.5). The data constituting the primary end-

STATISTICAL

points were collected at the investigative centers and

population was used for the efficacy analysis. The

independently adjudicated by an independent clin-

intention-to-treat population consisted of all patients

ical events committee (amputation, CD TLR, death) or

who underwent PTA, had post-PTA dissections iden-

by the DUS core laboratory (primary patency).

tified by the investigator, and had the Tack Endo-

STUDY OUTCOMES AND FOLLOW-UP. Periprocedural

vascular System advanced through the introducer

outcomes assessed included device success and pro-

sheath. The performance goal for this study was

cedure success. Device success was defined as suc-

derived from the lower limit of the 95% confidence

cessful deployment of the Tack(s) at the intended

interval for the DCB and PTA groups in the LEVANT 2

target site(s), successful withdrawal of the delivery

trial (28). It was hypothesized that the Tack Endo-

catheter from the introducer sheath, and Tack im-

vascular System would resolve dissections without

plant(s) remaining in position through completion of

negatively affecting primary patency at 12 months.

the index procedure. Procedure success was defined

On the basis of the LEVANT 2 results, the primary

as vessel patency (<30% residual stenosis by visual

patency rate was dependent on the type of balloon

estimate) without the use of a bailout stent or the

used, and therefore the performance goal was calcu-

occurrence of MAEs upon completion of the in-

lated using the proportion of patients enrolled who

dex procedure.

were treated with DCB or PTA. The sample size was

ANALYSIS. The

intention-to-treat

After procedure completion, follow-up was con-

calculated using PASS 2012, a 1-sample exact test,

ducted at 1, 6, and 12 months after the procedure.

power of 90%, 1-sided type I error controlled at 2.5%,

Evaluations conducted through follow-up included

and setting the maximum proportion of patients

DUS, RC, ankle-brachial index, peripheral artery

treated with DCBs enrolled at 60%. In this case, the

questionnaire (25), quality of life assessed using the

performance goal for primary patency at 12 months

EQ-5D-3L (26), and walking impairment question-

was 53%. Conservatively, the primary patency for

naire (27). Radiographic evaluation of Tack integrity

DCB plus Tack and control PTA plus Tack was

was conducted at 12 months and evaluated by the

assumed to be 65% for the purposes of the sample

angiographic core laboratory. The study was com-

size calculation. Using those assumptions, it was

plete with respect to the evaluation of the primary

estimated that 178 patients were required to have

endpoints at 12 months of follow-up.

data evaluable at 1 year for the primary efficacy

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TOBA II 12-Month Results

F I G U R E 2 Kaplan-Meier Curve for Primary Patency

all-cause death at 30 days). The percentage of patients with no MAEs within 30 days was calculated, along with an exact 1-sided 95% confidence interval. The objective of this endpoint was met if this confidence interval exceeded the pre-defined VIVA performance goal of 88% (24). Standard summary statistics were calculated for all patients and study outcome variables. Continuous variables were summarized using means and SDs. Categorical data were summarized using frequencies and percentages. Freedom-from-event analyses were conducted using the Kaplan-Meier methodology. Changes from baseline in RC, ankle-brachial index, and the questionnaires was evaluated using the Wilcoxon signed rank test or McNemar test. A p value <0.05 was considered to indicate statistical significance.

RESULTS Primary patency was defined as freedom from clinically driven target lesion revascular-

ENROLLMENT AND FOLLOW-UP. A total of 213 pa-

ization (as adjudicated by clinical events committee) and freedom from duplex

tients at 33 clinical sites in the United States and

ultrasound–derived binary restenosis (as adjudicated by core laboratory) at 12 months.

Europe were entered into the study. Among the

The number of subjects at risk are included at 90-day intervals.

enrolled patients, 195 (91.5%) completed the 12month follow-up, and 183 (85.9%) were evaluable

endpoint. On the basis of estimated attrition of 15%, enrollment of 210 patients was planned. The primary safety endpoint of the study was

for the primary efficacy endpoint with either a readable 12-month DUS study or angiogram or CD TLR prior to the end of the 12-month follow-up window.

freedom from the occurrence of any new-onset MAEs

DEMOGRAPHICS AND CLINICAL CHARACTERISTICS.

(above-the-ankle index limb amputation, CD TLR, or

Baseline demographic and clinical characteristics are summarized in Table 1. The mean age was 68.2
9.1

F I G U R E 3 Kaplan-Meier Curve for Freedom from Clinically Driven Target

Lesion Revascularization

years, and 151 of 213 (70.9%) were men. Most patients (95.7%) had claudication (RC 2 or 3), while the remaining 4.2% were classified in RC 4 with ischemic rest pain. The most common comorbidities were hypertension (89.7%) and hyperlipidemia (87.2%), and 60.7% had coronary artery disease. Treated lesions were primarily de novo (94.8%), and the most common lesion location was the SFA (87.2%). The mean lesion length was 74.3
40.6 mm, and occlusions accounted for 23.2% of lesions. Moderate or severe calcification was present in 59.3% of the lesions. The mean pre-procedure stenosis was 73.5%. PROCEDURAL OUTCOMES. Table 2 summarizes pro-

cedural data and outcomes. The study distribution of balloon types was 42.3% standard balloons and 57.7% DCBs, on the basis of operator choice during the index procedure. A total of 417 dissections were site reported, while 369 dissections (99.5%) were adjudicated by the core laboratory, with a mean of 1.8
0.9 dissections per patient. The average dissection length Freedom from clinically driven target lesion revascularization (CD-TLR) at 12 months. The number of subjects at risk are included at 90-day intervals.

was 20.7 mm. Dissection grades were reported both for all dissections and for the most severe dissection for each

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TOBA II 12-Month Results

patient. In general, the investigator and core laboratory analyses were similar for dissection grade. A

F I G U R E 4 Rutherford Category Improvement

majority of the dissections were severe, with the core laboratory identifying 69.4% of patients having dissections grade C or higher. Table 3 contains data on the number and grade of dissections. All patients received at least 1 Tack implant during the procedure, with an average of 4.1 Tacks deployed per patient (range 1 to 15 Tacks). Two hundred thirtynine Tack catheters were introduced for use into the 213 patients, with a total of 871 Tacks implanted. All but 9 devices successfully delivered Tacks to the desired location and, the device success per patient was 204 of 213 (95.8%). Procedure success was achieved in 212 of 213 patients (99.5%), with only 1 patient requiring a bailout stent. After Tack treatment, 92.1% of all dissections were completely resolved as adjudicated by the core laboratory. SAFETY EVALUATION. There were no MAEs associ-

ated with the primary safety endpoint reported

Rutherford category changes from baseline (p < 0.0001 from baseline).

through the 30 days of follow-up, thus meeting the pre-defined performance goal of 88% being MAE free (p < 0.0001).

cohort.

There

was

significant

improvement

(p < 0.001) from baseline to all follow-up visits in the

PRIMARY EFFICACY ENDPOINT. DUS follow-up or

5 peripheral artery questionnaire functional cate-

documented occurrence of a TLR was available for 183

gories (physical function, stability, symptoms, quality

patients (85.9%) at 12 months. The Tack implant met

of life, and social limitation) and overall. In the EQ-

the primary endpoint by exceeding the target perfor-

5D-3L, patients reported significant (p < 0.05)

mance goal of 52.7% (p ¼ 0.0006). The binary estimate for primary patency in the intention-to-treat popula-

improvement in mobility, usual activity, pain or discomfort, and visual analog scale score for state of

tion was 65.6%, with a 95% lower confidence bound of

health. There was no significant (p > 0.05) change

58.2%.

from baseline self-care or anxiety or depression.

The

Kaplan-Meier

patency

estimate

at

12 months is 79.3% (Figure 2). The median length of

Similarly, the walking impairment questionnaire

follow-up was 364 days (interquartile range: 337 to

showed significant (p < 0.0001) improvement over

378 days). Through 12 months of follow-up, the rate of MAEs remained acceptably low: no major amputations were reported, and 4 deaths occurred, none of which were attributed to the device or the procedure. Thirty-

F I G U R E 5 Ankle-Brachial Index Improvement

one CD TLRs occurred. The Kaplan-Meier freedom from CD TLR at 12-month window is 86.5% (Figure 3). ADDITIONAL

FOLLOW-UP

EVALUATIONS. There

was a significant (p < 0.0001) improvement in RC over time (Figure 4). By protocol, all patients were in RC 2 to 4 at enrollment. At 12-month follow-up, 137 of 191 (71.7%) of patients reported either no symptoms or mild claudication (RC 0 or 1), and 81.2% of all patients improved by 1 or more RC from baseline to

12

months.

Likewise,

there

was

significant

(p < 0.0001) improvement in the ankle-brachial index in the target limb from baseline through all follow-up visits (Figure 5). The data from the peripheral artery questionnaire, EQ-5D-3L, and walking impairment questionnaire are consistent with improved outcomes in this patient

Ankle-brachial index (ABI) changes from baseline (p < 0.0001 from baseline).

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TOBA II 12-Month Results

T A B L E 4 Standard Balloon Versus Drug-Coated Balloon Subgroup Comparison

Lesion length, mm

All

Standard Balloon

Drug-Coated Balloon

p Value

74.3
40.6 (N ¼ 210)

59.8
35.8 (n ¼ 90)

85.1
40.6 (n ¼ 120)

<0.0001

49/211 (23.2)

8/90 (8.9)

41/121 (33.9)

<0.0001

12/211 (5.7)

5/90 (5.6)

7/121 (5.8)

Total occlusion Severe calcification Dissection grade >C

145/209 (69.4)

62/89 (70.0)

83/120 (69.4)

Primary patency at 12 months

79.3 (73.1–84.3)

89.6 (81.0–94.5)

71.9 (62.8–79.1)

Values are mean
SD, n/N (%), or % (95% confidence interval). Based on core laboratory evaluation.

time in the overall assessment as well as each of the 3

improvement in measures of patient outcome in the

individual components (distance, speed, and stair).

clinical, hemodynamic, functional, and satisfaction

TACK ENDOVASCULAR SYSTEM STABILITY AND DURABILITY. Radiographic images at 12 months were

available for 730 implanted Tacks in 186 patients. Independent adjudication of these images showed that there were no Tack fractures. Furthermore, there was no evidence of Tack embolization. Only 1 minor migration was reported, which consisted of 2.6 mm of movement in a single Tack implant. No adverse events were reported in this patient, and the artery remained patent at 12 months.

domains. This study confirms and expands upon the results obtained from earlier studies of the Tack Endovascular System. In the first human experience in 15 limbs in 11 patients (25 lesions) with the Tack device, technical success was achieved in all cases and 1 year angiographic patency was 83.3% (8). Similarly, in the TOBA study, which was conducted in 130 patients with 74% with grade $C dissections following POBA angioplasty, the 12-month patency was 76.4%, and freedom from TLR was 89.5% (29). A pilot study

EVALUATION OF DCB AND POBA SUBGROUPS.

conducted in 32 patients with below-the-knee lesions

Although the study was not powered to assess for

(TOBA-BTK) also exhibited a high 12-month patency

differences in outcomes by type of balloon type used,

rate of 78.4% by vessel and 77.4% by patient, and

we conducted an exploratory analysis of balloon type

freedom from CD TLR was 93.5% (30).

subgroups (summarized in Table 4). As balloon type

The outcomes of this study compare favorably with

was chosen according to physician preference, lesions

published results of the randomized trials that

treated with DCBs tended to be more complex, with

compared POBA with DCB. Of note, in our cohort,

significantly longer lesions (85.1
40.6 mm vs. 59.8


patients treated with standard balloons had better

35.8 mm; p < 0.0001) and significantly more occlu-

primary patency at 12 months than did the DCB group.

sions (33.9% vs. 8.9%; p < 0.0001). There were,

This is likely related to fact that the DCB patients

however, no differences (p > 0.05) in the number of

were more complex, with longer lesions and more

patients with moderate to severe calcification or with

total occlusions that pre-disposed them to worse

dissection severity grade $C. The primary patency at

outcomes. These TOBA II results differ from those

12 months for the POBA subgroup was 89.6%, with a

published in randomized control trials comparing

lower confidence bound of 81.0%. The primary

DCB with POBA. In the LEVANT 2 trial, the 12-month

patency for the DCB subgroup in the same time frame

Kaplan-Meier primary patency rate was significantly

was 71.9%, with a lower confidence bound of 62.8%

greater for the DCB group (73.5% vs. 56.8%; p < 0.001)

(Central Illustration).

(13). IN comparison, the more complex DCB TOBA II lesions had similar primary patency, and the POBA

DISCUSSION

group of similar complexity fared substantially better. The positive outcomes of the TOBA II study are all

The prospective multicenter TOBA II study demon-

the more remarkable in that all enrolled patients had

strated that in a population composed exclusively of

post-treatment dissections, and many of them were

patients with post-angioplasty dissection after POBA

severe (w70% grade >C). Because patients with sig-

or DCB, the use of Tacks was successfully and safely

nificant dissections were programmatically excluded

able to repair dissections in the SFA or PPA, with an

from the DCB trials, LEVANT 2 reported a 7.5% rate of

improvement in 1-year patency outcomes compared

dissection grade $C (13).

with an objective performance goal and no device

Overall, these data provide evidence that Tacks

failures. Tacking was associated with sustained

can improve post-treatment outcomes in dissected

Gray et al.

JACC: CARDIOVASCULAR INTERVENTIONS VOL. 12, NO. 23, 2019 DECEMBER 9, 2019:2375–84

TOBA II 12-Month Results

vessels. Unlike stents, Tacks are composed of a min-

both safe and effective for focal dissection repair

imal metal scaffold of very short length. Although

following standard and DCB angioplasty of the SFA

Tacks, like stents, also facilitate the apposition of

and PPA.

dissection flaps to the luminal surface, they use lower radial outward force to minimize the biological effect and resultant hyperplastic response (31–33). This minimalist approach has other potential benefits. If future treatment is required, the reduced metal

ADDRESS FOR CORRESPONDENCE: Dr. William A.

Gray, Lankenau Heart Pavilion, 100 East Lancaster Avenue, Wynnewood, Pennsylvania 19096. E-mail: [email protected].

burden, compared with stents, allows multiple potential options to be considered. STUDY LIMITATIONS. TOBA II was conducted as a

PERSPECTIVES

single-arm study without an active control group. However, the performance goal for the efficacy

WHAT IS KNOWN? Dissection is the mechanism by which an-

endpoint was derived from a recent study with

gioplasty and is often underestimated in frequency and severity.

similar inclusion criteria. The performance goal for

Balloon angioplasty creates luminal gain, but dissection can

the safety endpoint has been widely used in assessing

negatively affect acute and long-term clinical outcomes.

safety of studies with similar patients. Also, this study was not powered to detect differences in

WHAT IS NEW? Focal dissection repair, after standard or DCB

balloon type used. The observed differences could be

angioplasty, using a minimal metal implant, improves vessel

due to a variety of factors, including operator bias for

patency without the drawbacks of conventional stenting.

balloon selection according to patient and lesion characteristics or some other factor, and require

WHAT IS NEXT? Peripheral dissections are classified using the

further evaluation.

National Heart, Lung, and Blood Institute system intended for the coronary arteries. A dissection index classification (number and severity of dissections within a single vessel) specific to the

CONCLUSIONS

peripheral vasculature could identify post-PTA dissections at

The TOBA II study results support the use of the Tack

higher risk for restenosis.

Endovascular System as a therapeutic option that is

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KEY WORDS angioplasty, dissection, femoropopliteal artery, peripheral artery disease