Balloons and Stents in Endovascular Therapy

Abstract

Endovascular treatment for patients with lower extremity artery disease (LEAD) has expanded its indications owing to the evolution of devices, improvements in techniques, and the establishment of clinical evidence. In particular, improvements in balloon and stent performance have significantly contributed to improved treatment outcomes. Herein, we describe the current status of basic balloon- and stent-related topics for the treatment of LEAD. (This is a translation of Jpn J Vasc Surg 2024; 33: 281–288.)

Introduction

In recent years, the indications for endovascular therapy (EVT) for lower extremity artery disease (LEAD) have been expanding in association with the evolution of devices, improvement of techniques, and establishment of evidence. In particular, improvements in balloon and stent performance have greatly contributed to improved treatment outcomes. However, with the diversification of devices, treatment and device selection have become increasingly complex. In this article, we describe the basic aspects regarding balloons and stents related to LEAD, with reference to some devices.

I. Balloon

Balloon catheters are used in a wide variety of ways, including percutaneous transluminal angioplasty (PTA), thrombectomy, vascular occlusion, prevention of embolism, and assistance when performing EVT, among others. In this section, we explain the PTA balloons used in the LEAD.

For balloon catheters, the compatible sheath size is determined according to the balloon diameter, balloon length, and shaft length, and they are selected depending on the diameter of the target vessel and the length of the lesion, as well as the condition of the access vessel. Balloon length is not the entire length of the balloon; it is the length obtained by subtracting the shoulder portions from the total balloon length. As it corresponds to the distance between markers, careful interpretation is required.

Balloon catheters are classified into 3 types—0.014, 0.018, and 0.035 inch—based on the inner diameter of the guidewire lumen. They can also be classified as over-the-wire (OTW) or monorail (MR) based on the guidewire passage method (Fig. 1). In the OTW system, the guidewire passes through the entire shaft. As the guidewire and catheter are coaxial, pushability is high, making it more effective for subintimal approaches and the treatment of occlusive lesions. However, balloon catheter exchange is more complicated. In contrast, in the MR system, the guidewire protrudes from the middle of the catheter shaft—a configuration sometimes referred to as “rapid exchange” (RX). As the guidewire does not run the entire length of the shaft in the MR system, balloon catheter exchange is easier (Table 1).

Fig. 1. OTW and MR. OTW: over-the-wire; MR: monorail.

Table 1. Over-the-wire and monorail balloon catheter.

	Over-the-wire type		Monorail type
Length of guidewire required	Long	< < <	Short
Guidewire replacement	Possible	> > >	Not possible
Balloon replacement	Complicated	< < <	Easy
Pushability	High	> > >	Low

An inflation device is used to pressurize the balloon when using a balloon catheter, and for each balloon, the nominal pressure (NP) and rated burst pressure (RP) are defined. NP is the pressure at which the balloon reaches the specified diameter, and RP is the pressure at which 99.9% of the balloons do not rupture. Depending on the ease with which the balloon expands, balloons are classified into 3 types: compliant, semicompliant (semicompliant), and non-compliant. Compliant balloons that expand along the vessel wall are rarely used in the treatment of lower extremity arterial disease (they are not suitable for lesion dilation), and semicompliant or noncompliant balloons are used in most cases. Higher compliance (ease of expansion) is synonymous with a lower NP, and the order is compliant > semi-compliant > non-compliant.

In general, balloons with high compliance have soft materials and high flexibility, excellent trackability in tortuous vessels, and high crossability, recross, and re-wrap performance. The target lesions included angulated and distal lesions below the knee. However, because the material is soft, it also elongates markedly in the longitudinal direction when the diameter expands; pressure may easily escape to easily expandable segments (normal vessels without lesions), resulting in dog-boning. In this state, stenosis is not resolved, and the normal vessels proximal and distal to the lesion may be injured; thus, caution is required. Noncompliant balloons do not expand beyond the specified balloon diameter regardless of the pressure; therefore, they can be expanded at high pressure and are less likely to dog-bone and cause vessel injury. Their indications include hard lesions (especially calcified lesions) (Table 2).

Table 2. Semicompliant balloon and noncompliant balloon.

	Semicompliant balloon		Noncompliant balloon
Compliance	High (easily inflated)	> > >	Low (hard to inflate)
NP/RP	Low	< < <	High
Flexibility	High	> > >	Low
Crossability	High	> > >	Low
Balloon material	Flexible	< < <	Hard
Elongation in front-back direction (Doggy bone)	Easily extended	> > >	Hard to extend
Target	Bending, below-knee lesions		Severely calcified, straight lesions

NP: nominal pressure; RP: rated burst pressure

One of the most important points to be cautious about during PTA in the LEAD is balloon dilation-induced vessel dissection. Measures to reduce the likelihood of dissection include selecting a balloon length longer than the lesion, maintaining dilation for a long duration of at least 3 min, not selecting an excessively large balloon diameter relative to the target vessel, performing inflation and deflation slowly, and not placing the shoulder on the lesion. In addition, with semicompliant balloons, dilation beyond the NP may produce a dog-bone-like shape and readily cause injury to normal vessels because the balloon is soft. Additionally, the balloon may expand in a twisted manner because the shaft does not elongate while the balloon elongates longitudinally, which can cause vessel dissection; thus, caution is required.

The balloon diameter selection is important not only for preventing dissection but also for obtaining acute gain. To select the balloon diameter, it is desirable to measure using contrast-enhanced computed tomography (CT), angiography, or intravascular ultrasound (IVUS). Among these, the reference vessel diameter (RVD) evaluation by angiography may be underestimated because it measures only the luminal diameter, and caution is required. The external elastic membrane (EEM) can be visualized when using IVUS with high spatial resolution, making it possible to measure the true RVD, including the plaque (Fig. 2).¹⁾ In principle, when an accurate RVD has been measured, the same balloon size is recommended. However, reimbursement may not be available depending on the region.

Fig. 2. IVUS finding. EEM (arrow). IVUS: intravascular ultrasound; EEM: external elastic membrane.

Balloon catheters are classified as specified medical materials into general/standard type, general/special type, cutting type, and others (for aortic stent grafts, anti-slipping type, etc.). Cutting- and anti-slipping-type balloons are equipped with elements around the balloon and are used in cases that are difficult to dilate, such as calcified lesions, and are expected to enhance vessel expandability by creating fissures in the intima. The Peripheral Cutting Balloon (Boston Scientific, Marlborough, MA, USA), UltraScore Focused Force PTA balloon (BD, Franklin Lakes, NJ, USA), Vascutrak PTA Dilatation Catheter (BD), AngioSculpt PTA Scoring Balloon Catheter (Spectranetics, Colorado Springs, CO, USA), and NSE PTA Balloon Catheter (Nipro, Osaka, Japan) are available in Japan. However, more specialized balloons, such as a high-pressure balloon (SHIDEN HP; Kaneka Medix, Tokyo, Japan) and a high crossability balloon (Oceanus PTA balloon dilatation catheter; iVascular, Barcelona, Spain), have also been marketed.

Drug-coated balloon

In the femoro-popliteal (F–P) artery region, PTA with balloons alone had problems with long-term patency, with a 3-year patency rate of 50%. Intimal hyperplasia after PTA is the most problematic trigger. The drug-coated balloon (DCB), in which a drug is coated on the balloon, has been developed to prevent this. In Japan, paclitaxel is the only drug used for DCB, and IN.PACT Admiral (Medtronic, Dublin, Ireland), Lutonix RX Drug-Coated Balloon (BD), and Ranger Paclitaxel-Coated PTA Balloon Catheter (Boston Scientific) are marketed (Table 3). For the use of DCB, the appropriate use guidance created jointly by 3 societies (Japanese Society for Vascular Surgery, Japanese Society of Interventional Radiology [IVR], and Japanese Association of Cardiovascular Intervention and Therapeutics) should be kept in mind.

Table 3. Drug-coated balloon (paclitaxel dose, μg/mm²; GW diameter; GW type; ISR indication or not; sheath compatible size).

Lutonix (2 μg/mm2, 0.014 inch, Monorail type ISR available, 5 Fr)
$\bcancel{\begin{array}{c}\begin{array}{l}\text{\hspace{1em}\hspace{1em}Length}\\ \end{array}\\ \text{Diameter\hspace{1em}\hspace{1em}\hspace{1em}\hspace{0.17em}}\end{array}}$	40 mm	60 mm	80 mm	100 mm	120 mm	150 mm	200 mm	300 mm
4 mm		✓				✓	✓	✓
5 mm		✓		✓		✓	✓	✓
6 mm		✓		✓		✓	✓	✓
7 mm
Ranger (2 μg/mm2, 0.018 inch, over-the-wire type, ISR not available, 5/6 Fr)
$\bcancel{\begin{array}{c}\begin{array}{l}\text{\hspace{1em}\hspace{1em}Length}\\ \end{array}\\ \text{Diameter\hspace{1em}\hspace{1em}\hspace{1em}\hspace{0.17em}}\end{array}}$	40 mm	60 mm	80 mm	100 mm	120 mm	150 mm	200 mm	300 mm
4 mm		✓		✓		✓	✓
5 mm		✓		✓		✓	✓
6 mm		✓		✓		✓	✓
7 mm		✓		✓
IN.PACT Admiral (3.5 μg/mm2, 0.035 inch, over-the-wire, ISR available, 5/6/7 Fr)
$\bcancel{\begin{array}{c}\begin{array}{l}\text{\hspace{1em}\hspace{1em}Length}\\ \end{array}\\ \text{Diameter\hspace{1em}\hspace{1em}\hspace{1em}\hspace{0.17em}}\end{array}}$	40 mm	60 mm	80 mm	100 mm	120 mm	150 mm	200 mm	300 mm
4 mm	✓	✓	✓		✓	✓
5 mm	✓	✓	✓		✓	✓
6 mm	✓	✓	✓		✓	✓
7 mm	✓	✓	✓

GW: guidewire; ISR: in-stent stenosis

To sufficiently exert the drug effect of DCB and obtain better outcomes, it is recommended that after dilation (predilation) with a balloon of the same size as the target vessel diameter, adequate dilation is achieved (residual stenosis <50%) and there is no severe dissection (grade D or higher) (Fig. 3).²⁾

Fig. 3. NHLBI classification system for intimal tears. NHLBI: National Heart, Lung and Blood Institute.

The IN.PACT superficial femoral artery (SFA) trial is a multicenter prospective randomized (IN.PACT:PTA = 2:1) single-blind trial consisting of 2 trials: the IN.PACT SFA I trial conducted in Europe (150 enrolled patients) and the IN.PACT SFA II trial conducted in the United States (181 enrolled patients). The primary patency rate at 1 year was 82.2% for IN.PACT and 52.4% for PTA (p <0.001).³⁾ In addition, in the IN.PACT SFA Japan trial conducted in Japan, the 1-year PTA was 89.2% for IN.PACT and 48.4% for PTA (p <0.001).⁴⁾

The RANGER II SFA trial is a single-blind randomized controlled trial (Ranger:PTA = 3:1) targeting patients with lesions with a length of ≤180 mm in the superficial femoral artery or proximal popliteal artery (Japan, the United States, Canada, Europe, and New Zealand), and the 1-year primary patency rate was 82.0% for Ranger and 68.8% for PTA (p = 0.0134).⁵⁾

The LEVANT II trial is a multicenter prospective randomized (Lutonix:PTA = 2:1) single-blind trial conducted in Europe and the United States in patients with lesion lengths of ≤150 mm. The 1-year primary patency rates were 65.2% and 52.6% for Lutonix and PTA, respectively (p = 0.02).⁶⁾ However, the LEVANT Japan trial conducted in Japan could not demonstrate efficacy, with a 1-year PTA rate of 58.0% for Lutonix and 62.9% for PTA.⁷⁾

Overall, DCB shows better outcomes compared with drug non-coated balloons, and it has become the first choice for treating short- to mid-length lesions in the SFA region.

Regarding drug dose, DCBs are classified into high dose (3.5 μg/mm²): IN.PACT, and low dose (2 μg/mm²): Ranger and Lutonix; however, in reports of the COMPARE trial (IN.PACT vs Ranger)⁸⁾ and the LANDMARK registry (IN.PACT vs Lutonix),⁹⁾ no differences in efficacy or complications due to drug dose were observed, and currently, DCB selection is made based on the characteristics of each device, including the balloon catheter (Table 3).

For DCB, at least dual antiplatelet therapy for ≥1 month is recommended, followed by continuation of aspirin monotherapy; however, there is no evidence regarding combination therapy with antiplatelet agents and anticoagulants, and further studies are warranted.

II. Stent

In Japan, stents are reimbursed for use in the aorto-iliac occlusive disease (AIOD) region and the superficial F–P region. No marketed devices are available for the common femoral artery or for disease below the knee; these remain non-stenting zones, and endarterectomy and bypass surgery are the first choices.

Stents are the first choice as scaffold devices in AIOD; however, in the F–P region, under the concept of “leave nothing behind,” use of the abovementioned DCB has been increasing, and the Japan-endovascular therapy (J-EVT) 2022 report¹⁰⁾ indicates that DCB use is approximately 50% (Fig. 4).

Fig. 4. J-EVT 2022¹⁰⁾. DCB: drug-coated balloon; BMS: bare metal stent; DES: drug-eluting stent; J-EVT: Japan-endovascular therapy.

Currently, bare metal stents (BMS), drug-eluting stents (DES), and covered stents (CS) are available and selected according to the characteristics of each region.

Stents are broadly classified into self-expandable and balloon-expandable according to the deployment method. Self-expandable stents are based on shape-memory alloys (nitinol/nickel and titanium alloys) and are deployed by releasing a constraining mechanism. In general, they exhibit excellent conformability, flexibility, and good restoration properties. In contrast, balloon-expandable stents are deployed by balloon expansion using materials such as stainless steel, cobalt–chromium alloys, and platinum–chromium alloys, which exhibit excellent ductility. In general, they have strong radial force and good deployment accuracy and are more useful for ostial lesions or recoil prevention in calcified lesions; however, no DESs have been reported (Table 4).

Table 4. Self-expandable stent and balloon-expandable stent.

	Self-expandable stent		Balloon-expandable stent
Material	Nitinol (nickel, titanium alloys), etc.		Stainless steel, cobalt-chrome alloy, platinum-chrome alloy, etc.
Extended strength/recoil resistance	Weak	< < <	Strong
Trackability/flexibility	High	> > >	Low
Diameter adjustment	Not possible	< < <	Possible
Deployment accuracy	Difficulty	< < <	Easy
Resilience to compression	High	> > >	Low
Target	Bending, long lesions		Orifice, calcification, short lesions

1. BMS

Medical-grade 316L stainless steel, tantalum, cobalt alloys, and nitinol (an alloy of nickel and titanium) were used. The manufacturing methods included laser cutting a metal tube, connecting short cells, and braiding wire.

2. DES

DES are devices in which drugs that suppress cell proliferation are coated on the surface of BMS, and improved patency is expected. The challenge of DES for LEAD began with the SIROCCO trial, which used a sirolimus-coated SMART stent (Cordis, Bridgewater, NJ, USA) coated with sirolimus.¹¹⁾ Sirolimus is a macrolide antibiotic discovered in the soil of Easter Island. It has strong immunosuppressive effects, and improvement of patency through suppression of neointimal proliferation was expected. However, it did not improve restenosis, partly because sirolimus is released from the stent over a short period (approximately 7 days).

Subsequently, the STRIDES trial using the Dynalink/Absolute stent (Abbott Vascular, Santa Clara, CA, USA) coated with everolimus¹²⁾ also did not yield the expected results. Next, the Zilver PTX stent (Cook Medical, Bloomington, IN, USA), which is the Zilver flex stent coated with paclitaxel, was approved in January 2012 after the first Japan–US simultaneous joint trial in Japan. Numerous clinical trials have been reported, and improvement in restenosis has been observed; however, drug release was short at approximately 60 days, and further improvement was necessary. It was considered essential to improve the polymer that coats the drug to extend the release period, and the Eluvia stent (Boston Scientific) pursued that quality. By using the proven PROMUS polymer to coat paclitaxel on the INNOVA stent (Boston Scientific), drug release could be extended to approximately 1 year.

Thereafter, the head-to-head IMPERIAL clinical trial comparing the Zilver PTX stent and the Eluvia stent was conducted, and the superiority of Eluvia was shown in 1-year primary patency.¹³⁾ Currently, the development of sirolimus-based DES is underway, with attention to lower biological toxicity, and improvement in therapeutic effect is expected, including the device platform.

3. Covered stents

Small-diameter CS have a stent covered with a graft (artificial vessel) and therefore have properties such as repairing disrupted vessels, covering mural thrombus to reduce embolism, and suppressing neointimal proliferation to prevent diffuse restenosis over the entire length of the deployed stent. However, their roles are also diverse.

In Japan, small-diameter stent grafts approved as medical devices are, in order of approval, GraftMaster (Abbott Vascular), VIABAHN stent graft, and VIABAHN VBX (W. L. Gore & Associates, Flagstaff, AZ, USA), and LIFESTREAM (BD), and indications are defined for each device (Table 5).

Table 5. Small-diameter covered stents available in Japan.

	GRAFT MASTER*	VIABHAN**	VIABAHN VBX**	LIFESTREAM***
Approval in Japan	2003	2016 (1, 2), 2020 (3)	2018	2021
Instruction for use	Bleeding due to the perforation of the coronary artery or the saphenous vein graft	1)Vascular injury 2)Atherosclerotic lesions of the superficial femoral artery extending to the popliteal artery 3)Stenosis of the anastomosis of the shunt in the dialysis artificial blood vessel	Iliac artery lesions	Iliac artery lesions
Balloon type	Balloon-expandable	Self-expandable	Balloon-expandable	Balloon-expandable
Stent material	316 stainless steel	Nitinol stent	Stainless steel	Stainless steel
Graft material	ePTFE	ePTFE	ePTFE	ePTFE
Stentgraft diameter (mm)	2.8–4.8	1) 5–13 2) 5–8 3) 5–8	5–11 (post-dilation: 8–16)	7–12 (post-dilation: 10–12)
Compatible guidewire diameter (inch)	0.014	0.018	0.035	0.035
Compatible guiding catheter diameter (Fr)	6–7	6–7	7–8	6–8

*Abbott Medical Japan.

**W. L. Gore & Associates.

***Bard Medical.

ePTFE: expanded polytetrafluoroethylene

3.1. Appropriate use guidance for LEAD VIABAHN in the SFA region

A committee for standards management of superficial femoral artery stent graft implementation was established by the Japanese College of Angiology, the Japanese Society of Interventional Radiology, the Japanese Society for Vascular Surgery, and the Japanese Association of Cardiovascular Intervention and Therapeutics, and appropriate use guidance, facility standards, and operator qualification standards have been defined. The indication is for improving blood flow in patients with symptomatic peripheral arterial disease with lesions in the SFA of RVD of 4.0–7.5 mm and target lesion length of 10 cm or more.¹⁴⁾

3.2. Appropriate guidance for VIABAHN use for iatrogenic/traumatic vascular injury

Experience equivalent to that of an IVR specialist, a cardiovascular surgery specialist, a society-certified endovascular therapist, a certified cardiovascular interventionist, or a vascular specialist is required when used for IVR or traumatic vascular injury. As appropriate use guidance, it can be used as an emergency procedure for patients in whom hemostasis is difficult or traumatic or iatrogenic vascular injury occurs in the thoracic, abdominal, or pelvic arteries. On the other hand, it is explicitly stated that it cannot be used in the aorta, coronary arteries, brachiocephalic arteries, carotid arteries, vertebral arteries, and pulmonary arteries.¹⁵⁾

3.3. Appropriate use guidance for balloon-expandable small-diameter CS for the AIOD region

As guidance for the target patients, the following is stipulated:

• 1.In principle, this approach should be used for iliac artery Trans-Atlantic Inter-Society Consensus (TASC) II type C/D lesions.
• 2.TASC II type A/B lesions should be treated only when they meet any of the following criteria and when the physician judges it clinically appropriate: (a) Application of the kissing stent technique for an aortic bifurcation lesion. (b) Complex lesions with a high risk of rupture or perforation after dilation, such as severely calcified or occlusive lesions (e.g., severely calcified lesions involving 2/3rd of the vessel wall circumference or complex lesions, such as occlusive lesions, confirmed by preoperative CT or ultrasonography).¹⁶⁾

VIABAHN VBX and LIFESTREAM are both balloon-expandable and have stents covered with expanded polytetrafluoroethylene (ePTFE). Therapeutic effects are expected in severely calcified cases, in which sufficient effects could not be obtained using BMS, and in thrombus-rich cases. A characteristic of CS is that post-dilation is possible by changing the diameter of the balloon. Size selection can be difficult because of the caliber difference in the iliac region; however, it is possible to select the device according to the smaller diameter and press the proximal side with a balloon.

The difference between the 2 CS devices is that VBX has a heparin coating and is expected to improve patency, whereas LIFESTREAM is mounted on a noncompliant balloon and can therefore be expanded more safely. In an experiment performing overexpansion including these 2 devices, VBX was shown to be less likely to recoil, whereas LIFESTREAM was less prone to shortening during overexpansion.¹⁷⁾ Selecting devices considering each characteristic and size lineup is necessary.

Conclusions

In this article, we described the basic aspects of stents and balloons. Fully understanding each characteristic and selecting appropriate devices is essential for safe and effective treatment, similar to the EVT technique.

Declarations

Author contributions

Study conception: TO, KK, EI

Investigation: KK, EI

Manuscript preparation: TO, KK, EI

Critical review and revision: all authors

Final approval of the article: all authors

Accountability for all aspects of the work: all authors.

Disclosure statement

Takao Ohki is a consultant for W. L. Gore & Associates. The other authors have no conflicts of interest.