Sirolimus-eluting balloon for the treatment of peripheral artery disease: SUCCESS PTA real-world single-arm study

Abstract

Background

Outcomes with sirolimus-coated drug-eluting balloons (DEB) have been positive for the treatment of femoropopliteal arterial lesions but have not been studied in a broader patient population.

Objectives

Collect real-world safety and effectiveness data on the SELUTION SLR DEB in patients with claudication and chronic limb-threatening ischemia (CLTI).

Methods

This international multi-center, prospective, single-arm, post-market study (SUCCESS PTA) enrolled 723 patients at 27 sites. The primary endpoint was freedom from clinically driven target lesion revascularization (CD-TLR) after 1 year.

Results

Median age was 71.0 [63.0–79.0] years, 65% were male, 25.7% had CLTI. In total, 822 lesions were included; median lesion length was 100.0 mm [50.0–190.0] with 42.1% chronic total occlusions and 36.4% moderate-to-severe calcification. At 12 months, freedom from CD-TLR was 91.1%, 95% CI [88.6–93.1] and 52.1% of patients were asymptomatic. Median EQ-VAS score and ankle-brachial pressure index improved significantly from baseline to 12 months (65.0 [50.0–80.0] vs. 75.0 [60.0–85.0] (p < 0.0001)) and (0.6 [0.5–0.8] vs. 0.9 [0.8–1.0] (p < 0.0001)), respectively.

At 12 months, outcomes in CLTI patients included major target limb amputation, 5.8%; major cardiac event rate, 4.3%; and death, 11.3%. Respective outcomes for those with claudication were 0.0%, 2.2% and 1.2%.

Conclusions

This real-world single-arm study is the largest assessment of a sirolimus DEB for treatment in claudication and CLTI. The outcomes were consistent with those reported for paclitaxel-coated balloons and support this DEB platform as a promising alternative, particularly in CLTI patients.

Level of evidence

Level 3.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s42155-026-00751-2.

Introduction

Drug-coated balloons (DCBs) have become a standard of care for the treatment of femoropopliteal disease because of their superior primary patency and target lesion revascularization rates compared to non-coated balloon angioplasty [1–8]. However, results from the SWEDEPAD 1 and SWEDEPAD 2 randomized controlled trials showed that paclitaxel-coated balloons fail to improve disease-specific quality of life in patients with claudication and amputation rates in CLTI patients [9, 10]. This has led to a shift in ESVS guideline recommendations of paclitaxel-coated balloons for asymptomatic peripheral artery disease (PAD) and intermittent claudication. As of 2026, ESVS recommends against routine use of paclitaxel-coated balloons for intermittent claudicant, citing a lack of quality of life benefit and the potential for long-term mortality risks [11]. In addition, studies on paclitaxel-coated balloons in below-the-knee (BTK) lesions have shown mixed positive and negative results, making their superiority over plain old balloon angioplasty (POBA) unclear [12–17].

A promising alternative to paclitaxel, which is a cytotoxic drug, may be represented by sirolimus. Sirolimus acts cytostatically to inhibit cell proliferation by reversibly putting the cells into the resting phase of mitosis (G₀). Sirolimus also has a larger local margin of safety, wider therapeutic window and anti-inflammatory effects [18]. Until recently, sirolimus could not be delivered on an angioplasty balloon platform because it is less lipophilic than paclitaxel, making its transfer and absorption into the vessel wall cumbersome. The SELUTION Sustained Limus Release (SLR™) Drug-Eluting Balloon (DEB, MedAlliance LLC (a Cordis Company), Irvine, USA) circumvents this limitation by using micro-reservoirs, a mix of sirolimus and biodegradable poly lactic-co-glycolic acid (PLGA), applied to the balloon surface using a proprietary blend of lipid-based excipients. This coating controls drug release and optimizes sirolimus transfer and adherence to the vessel wall using a nominal dose density (1 μg/mm²) on the balloon surface. Upon balloon expansion, these micro-reservoirs are transferred to the tissue and maximize delivery of drug to the surrounding cells. Sirolimus is eluted and absorbed slowly, with studies in coronary porcine models sustaining release up to 90 days [19, 20].

Early studies of the SELUTION SLR SEB have demonstrated high primary patency rates (typically > 85%), low target lesion revascularization rates (< 10%), and encouraging safety profiles across femoropopliteal and tibial disease [20–28]. Similarly, promising results have been shown of other limus-eluting devices within the SIRONA trial, which demonstrated non-inferiority to paclitaxel balloons, and in SirPAD, that demonstrated superiority to percutaneous transluminal angioplasty (PTA) in a mixed ATK/BTK setting [29, 30]. However, these studies have been limited by modest sample sizes, restricted lesion lengths, and selective inclusion criteria, often excluding patients with advanced disease or complex anatomy. The SUCCESS PTA study was designed to evaluate the performance of SELUTION SLR DEB in a broader and more clinically representative population in an international real-world setting. This post-market, all-comers single-arm study provides one of the largest assessments to date of sirolimus-eluting balloon angioplasty in peripheral arterial disease.

Methods

Study design

SUCCESS PTA Study is an open-label, real-world all-comers, prospective, multi-center, single-arm study. It enrolled patients from 27 centers in eight countries. The study protocol was approved by the ethics committee at each site, and the trial was registered with clinicaltrials.gov (NCT04776434). The trial was conducted in compliance with good clinical practice for medical devices and in accordance with ethical principles based on the Declaration of Helsinki.

Patient population

Patients undergoing treatment for peripheral arterial disease were eligible for this trial if they were ≥ 18 years of age and deemed by the operator suitable for treatment with the SELUTION SLR DEB. Patients with life expectancy of less than 12 months or those deemed, in the investigator’s judgment, unlikely to adhere to study follow-up were excluded.

Study device

The SELUTION SLR DEB is a 3.9 Fr (1.3 mm) diameter over-the-wire device compatible with a 0.018–inch guidewire, delivered via a 5–7 French access sheath depending on device size. The DEB diameters range from 2.0 to 7.0 mm with lengths of 20–150 mm.

Study procedure

Patients were treated per standard of care at each institution. Pre-dilation or vessel preparation such as atherectomy, thrombectomy and scoring balloons were performed in all cases. For this registry, lesion preparation was performed at the operator’s discretion with no restrictions, based on local practice and standard of care. A post-angioplasty angiogram was captured to document procedural outcomes. Lesion calcification was assessed per the PACCS classification [31]. In instances of residual stenosis > 30% or a flow-limiting dissection, investigators were permitted to follow standard-of-care bailout procedures at their discretion such as repeat PTA, repeat SELUTION SLR DEB and/or placement of a bail-out stent. Post-procedure dual anti-platelet treatment was prescribed per each institution’s standard of care.

Outcomes and follow-up

Resting ankle brachial pressure index (ABPI), Rutherford classification, EQ-5D and EQ-VAS data were collected at pre-procedure (within 30 days prior), 6 months, and 12 months post-procedure. Results are based on paired data and include only subjects with complete data at the relevant timepoints, and follow-up completed within the ± 30-day visit window. Adverse events, hospital resource utilization data and concomitant medications were also collected through 12 months. All events were assessed by the Cordis Sponsor Safety Office: site-reported information entered in the EDC system was reviewed to categorize the event (determine relevance to each study endpoint) and evaluate causal relatedness.

The primary endpoint was freedom from clinically driven target lesion revascularization (CD-TLR). Secondary endpoints included device success defined as successful delivery, balloon inflation, deflation, and retrieval of the intact device without burst below rated burst pressure; procedure success defined as device success with a final target lesion residual stenosis ≤ 50% at the end of the procedure with or without bail-out stenting. Additional secondary endpoints included EQ-5D and a change in Rutherford classification, ABPI, and EQ-VAS from baseline and any major adverse limb event (MALE), defined by the composite of severe limb ischemia leading to an intervention or major amputation (above the ankle).

Time to event analyses were conducted using the Kaplan–Meier method. Categorical variables are presented as frequencies and percentages, while continuous variables are summarized with median and inter-quartile range (IQR) as the p-value associated with the Shapiro–Wilk test to assess normality was < 0.05 for all continuous variables presented. Event proportions were calculated based on the number of eligible patients who completed follow-up or experienced the event of interest prior to follow-up and had complete data for the variable of interest. Signed-rank tests were used to test if the change from baseline to a follow-up time point was significant for ABPI and EQ-VAS. For Rutherford classification, the ordinal McNemar-Bowker test was used to test if the change from baseline to a follow-up time point was significant. Data was analyzed using Stata software (version 18.5, StataCorp College Station, Texas, USA).

Results

Study population and baseline characteristics

Between February 2021 and October 2023, 723 patients were enrolled at 27 sites (Supplemental Table 1). Of these, three withdrew consent and declined the use of their previously collected data, resulting in a final analysis population of 720 patients (Fig. 1). Baseline patient and lesion characteristics are shown in Table 1. Overall, the median age was 71.0 [63.0–79.0], 65.0% (468/720) of patients were male, 37.9% (273/720) had diabetes and 30.3% (217/715) were current smokers. Patient characteristics in those with claudication (n = 534) versus CLTI (n = 186) are listed in Table 1.

Fig. 1.

Patient flow diagram through 365 days (± 30 days)

Table 1.

Baseline patient characteristics

	Full cohort (N = 720 patients)	Claudicants (N = 534 patients)	CLTI (N = 186 patients)
Age (years)	71.0 [63.0–79.0]	71.0 [63.0–77.0]	74.0 [64.0–84.0]
Male	65.0% (468/720)	63.9% (341/534)	68.3% (127/186)
Diabetes mellitus	37.9% (273/720)	33.0% (176/534)	52.2% (97/186)
Insulin dependent	13.6% (98/720)	9.4% (50/534)	25.8% (48/186)
Previous intervention (< 1 year) at lesion	16.6% (119/718)	14.8% (79/532)	21.5% (40/186)
Hypertension	85.3% (614/720)	84.5% (451/534)	87.6% (163/186)
Hyperlipidemia	76.8% (553/720)	77.0% (411/534)	76.3% (142/186)
Cerebral stroke/transient ischemic attack	7.1% (51/720)	5.6% (30/534)	11.3% (21/186)
Myocardial infarction	14.9% (107/720)	15.0% (80/534)	14.5% (27/186)
Renal failure/impairment	16.8% (121/720)	12.7% (68/534)	28.5% (53/186)
Current smoker	30.3% (217/715)	31.8% (168/529)	26.3% (49/186)
Rutherford Categories (RC)
1	3.2%	4.3%*	NA
2	21.4%	28.8%	NA
3	49.4%	66.7%	NA
4	8%	NA	31.2%
5	16.5%	NA	64%
6	1.2%	NA	4.8%
Ankle-Brachial Pressure Index (ABPI)	0.6 [0.5, 0.8] (598)	0.7 [0.5, 0.8] (463)	0.6 [0.4, 0.8] (135)

Data are presented as percentages % (n/N) or median [IQR]. Values represent total n unless otherwise specified

^*There were 23 patients (27 lesions) classified as Rutherford 1, 85% of lesions were de novo, 78% had ≥ 80% stenosis, all had more than 50% stenosis and were enrolled per investigator discretion. NA for not applicable

Most lesions were de novo (75.1%) with a median lesion length of 100.0 [50.0–190.0] mm; 42.1% were chronic total occlusions and 36.4% were moderately to severely calcified. Baseline lesion characteristics are provided in Table 2.

Table 2.

Baseline lesion characteristics

	Full cohort (N = 822 lesions)	Claudicants (N = 604 lesions)	CLTI (N = 218 lesions)
Reference vessel diameter (mm)	5.0 [5.0–6.0] (821)	5.2 [5.0–6.0]	5.0 [4.0–6.0] (217)
Lesion length (mm)	100.0 [50.0–190.0] (818)	100.0 [45.0–200.0] (601)	100.0 [50.0–180.0] (217)
De novo lesion	75.1% (617/822)	75.2% (554/604)	74.8% (163/218)
Restenotic lesion˚	24.9% (205/822)	24.8% (150/604)	25.2% (55/218)
Diameter stenosis (%)	98.0 [90.0–100.0]	95.0 [90.0–100.0]	99.0 [90.0–100.0]
Total occlusion	42.1% (346/822)	41.7% (252/604)	43.1% (94/218)
Located above-the-knee*	81.0% (666/822)	85.9% (519/604)	67.4% (147/218)
SFA prox	38.3% (255/666)	37.8% (196/519)	40.1% (59/147)
SFA mid	50.2% (334/666)	52.4% (272/519)	42.2% (62/147)
SFA dis	52.0% (346/666)	48.7% (253/519)	63.3% (93/147)
POP 1	30.3% (202/666)	26.6% (138/519)	43.5% (64/147)
POP 2	21.8% (145/666)	19.3% (100/519)	30.6% (45/147)
Other**	2.9% (19/666)	2.9% (15/519)	2.7% (4/147)
Located below-the-knee*	19.0% (156/822)	14.1% (85/604)	32.6% (71/218)
POP 3	42.3% (66/156)	54.1% (46/85)	28.2% (20/71)
Anterior tibial	23.7% (37/156)	14.1% (12/85)	35.2% (25/71)
Posterior tibial	9.6% (15/156)	5.9% (5/85)	14.1% (10/71)
TP trunk	9.6% (15/156)	5.9% (5/85)	14.1% (10/71)
Peroneal	5.1% (8/156)	3.5% (3/85)	7.0% (5/71)
Other**	7.7% (12/156)	9.4% (8/85)	5.6% (4/71)
Median lumen diameter (mm)	0.5 [0.0–1.0] (816)	0.5 [0.0–1.0] (599)	0.1 [0.0–1.0] (217)
PACCS calcification grade 3†	20.1% (165/821)	19.9% (120/603)	20.6% (45/218)
PACCS calcification grade 4†	16.3% (134/821)	15.6% (94/603)	18.3% (40/218)

Data are presented as percentages % (n/N) or median [IQR]. Values represent total n unless otherwise specified

˚Includes in-stent restenosis and native vessels

^*One lesion can cross multiple segments; above-the-knee: proximal target lesion origin of Pop 2 and above (including common femoral), below-the-knee: any lesion including segments below POP2, BTK lesions either isolated or combined with inflow (ATK) lesions

^**For ATK: Profunda, iliac, bypass; For BTK: bypass, dorsalis, plantar

^†Peripheral Arterial Calcium Scoring System (PACCS) Grade 3: bilateral calcification < 5 cm, Grade 4: bilateral calcification ≥ 5 cm

Interventional procedure

Lesion preparation was performed in 98.8% of lesions, most commonly with standard balloon angioplasty (84.1%). Adjunctive techniques included atherectomy (22.2%), scoring balloons (4.1%), intravascular lithotripsy (3.8%) and thrombectomy (3.3%). Bail-out stenting occurred in 32.0% of the cases. The bail-out lesions had a median length of 150 mm. Additional procedure details are provided in Table 3. Device success was achieved in 99.0% of cases and procedure success was noticed in 97.9% of patients. 13 patients did not achieve device success (9 issues with deployment, 2 issues with inflation/deflation and 2 ruptures).

Table 3.

Procedural characteristics

	Full cohort (N = 822 lesions)	Claudicants (N = 604 lesions)	CLTI (N = 218 lesions)
Lesion preparation	98.8% (809/819)	98.5% (593/602)	99.5% (216/217)
Device type for lesion preparation
POBA*	84.1% (677/805)	84.9% (502/591)	81.8% (175/214)
Atherectomy**	22.2% (179/805)	22.0% (130/591)	22.9% (49/214)
Thrombectomy	3.3% (27/805)	2.9% (17/591)	4.7% (10/214)
Scoring balloon	4.1% (33/805)	3.2% (19/591)	6.5% (14/214)
IVL*	3.8% (31/805)	3.7% (22/591)	4.2% (9/214)
Cutting balloon	1.7% (15/805)	1.9% (11/591)	1.9% (4/214)
Bail-out stenting˚	32.0% (263/822)	33.8% (204/604)	27.1% (59/218)
Reason (could be more than 1)
Residual stenosis > 30%	50.9% (134/263)	52% (106/204)	45.8% (27/59)
Flow limiting dissection	48.3% (127/263)	50% (102/204)	52.5% (31/59)
Other†	6.5% (17/263)	4.9% (10/204)	11.9% (7/59)
Final residual stenosis (%)	10.0 [0.0–20.0] (821)	10.0 [0.0–20.0] (603)	10.0 [0.0–15.0] (218)
Device success	99.0% (1296/1309‡)	99.2% (940/948‡)	98.6% (356/361‡)
Procedure success	97.9% (705/720)	98.3% (525/534)	96.8% (180/186)

Data are presented as percentages % (n/N) or median [IQR]. Values represent total n unless otherwise specified

^*POBA plain old balloon angioplasty, IVL intravascular lithotripsy

^**Type of atherectomy included 140 rotational, 20 directional, 7 orbital, and 12 were not reported

˚Median lesion length of lesions with bail-out stenting was 150 mm

^†Other reasons included calcification [2], recoil [11], and thrombus [4]

^‡Total number of devices

Device Success: Successful delivery, balloon inflation, deflation and retrieval of the intact study device without burst below rated burst pressure

Procedure Success: Device success and residual stenosis ≤ 50% at the end of the procedure

Clinical outcomes

In total, 645 and 629 patients completed follow-up at 6 months and 12 months, respectively. Freedom from CD-TLR was 97.5%, 95% CI [96.1, 98.5] at 6 months and 91.1%, 95% CI [88.6–93.1] at 12 months for the full cohort (Fig. 2). At 12 months, freedom from CD-TLR was 91.3% 95% CI [88.5, 93.5] for claudicants and 90.3%, 95% CI [84.0, 94.2] for CLTI patients. The cumulative MALE rate for the full cohort was 5.9% and 13.2% at 6 and 12 months, respectively. In the full cohort, major target limb amputation rates were 1.1% at 6 months and 1.3% at 12 months, while no amputations were performed in the claudicant group and eight major target limb amputations (5.8%) were performed in the CLTI group. Death rates were 1.8% at 6 months and 3.5% within 12 months of the procedure for the full cohort, 1.2% in claudicants and 11.3% in CLTI patients at 12 months. Clinical outcomes are summarized in Table 4.

Fig. 2.

Freedom from clinically driven target lesion revascularization through 365 days

Table 4.

Clinical outcomes at 6 and 12 months

Outcomes	Full Cohort		Claudicants		CLTI
	6 Months	12 Months	6 Months	12 Months	6 Months	12 Months
Death	1.8% (12/657)	3.5% (23/652)	0.2% (1/501)	1.2% (6/501)	7.1% (11/156)	11.3% (17/151)
Major cardiac event1	1.1% (7/649)	2.7% (17/636)	0.8% (4/501)	2.2% (11/497)	2.0% (3/148)	4.3% (6/139)
Clinical driven target lesion revascularization	2.6% (17/646)	9.0% (57/631)	2.2% (11/501)	8.7% (43/496)	4.1% (6/145)	10.4% (14/135)
Thrombosis	0.8% (5/647)	0.8% (5/629)	0.4% (2/500)	0.4% (2/495)	2.0% (3/147)	2.2% (3/134)
Target limb amputation	1.9% (12/647)	2.1% (13/634)	0.0% (0/500)	0.0% (0/496)	8.2% (12/147)	9.4% (13/138)
Major target limb amputation	1.1% (7/646)	1.3% (8/633)	0.0% (0/500)	0.0% (0/496)	4.8% (7/146)	5.8% (8/137)
Rutherford Class 4		12.5% (1/8)
Rutherford Class 5		50% (4/8)
Rutherford Class 6		37.5% (3/8)
Minor target limb amputation	0.8% (5/646)	0.8% (5/630)	0.0% (0/500)	0.0% (0/495)	3.4% (5/146)	3.7% (5/135)
MALE2	5.9% (38/648)	13.2% (84/638)	4.2% (21/501)	11.4% (57/498)	11.6% (17/147)	19.3% (27/140)

Denominators reflect the number of patients with available data for each variable; totals may vary due to missing or incomplete data

¹Major Cardiac Event: myocardial infarction, stroke, cardiovascular death

²Major Adverse Limb Event (MALE)-severe limb ischemia leading to an intervention to target limb or major vascular amputation

A paired analysis of the full cohort showed that Rutherford categories (RC) significantly improved at 6 months compared with baseline values and improvements were sustained after 12 months (p < 0.0001, vs baseline). In total, 52.2% were asymptomatic at 12 months and 88.1% improved by at least one RC from baseline (Fig. 3).

Fig. 3.

Rutherford classification, EQ-5D and EQ-VAS outcomes

The full cohort median EQ-VAS score improved significantly from 65.0 [50.0–80.0] at baseline to 75.0 [60.0–85.0] after 6 months (p < 0.0001) and was sustained after 12 months 75.0 [60.0–85.0] (p < 0.0001, Fig. 3). A paired analysis of EQ-VAS data (n = 405) for patients with claudication at baseline, 6 months, and 12 months showed an improvement from 65.0 [50.0, 80.0] to 75.0 [60.0, 85.0] and 75.0 [60.0, 85.0] (p < 0.0001). The paired analysis of EQ-VAS data (n = 93) at baseline, 6 months, and 12 months in CLTI patients showed improvement from baseline 60.0 [50.0, 70.0] to 70.0 [50.0, 80.0] at 6 months (p < 0.0001) and then 65.0 [50.0, 80.0] at 12 months (p = 0.0132).

Likewise, the resting ABPI improved significantly in the full cohort from baseline (06 [0.5–0.8]) to 0.9 [0.8, 1.0] at 6 months and remained high (0.9 [0.8–1.0]) after 12 months (p-value < 0.0001 vs. baseline). ABPI data in patients with claudication at baseline, 6 months and 12 months (n = 307) showed a median baseline of 0.7 [0.5, 0.8], improving to 0.9 [0.8, 1.0] at 6 months and 0.9 [0.8, 1.1] at 12 months (p < 0.0001). A paired analysis of ABPI in CLTI patients (n = 59) showed a baseline median of 0.6 [0.4, 0.8] improving to 0.9 [0.8, 1.0] at 6 months and 0.9 [0.8, 1.0] at 12 months (p < 0.0001).

Discussion

The SUCCESS PTA study demonstrated an overall CD-TLR rate of 9.0% at 1 year. These real-world outcomes are encouraging for the adoption of sirolimus-eluting balloons considering the inclusion of CTLI patients and below-the-knee disease. In a Delphi consensus for definitive treatment strategies of femoropopliteal lesions, vascular specialists from different countries and disciplines showed high agreement rates for the use of DCBs, including sirolimus-coated balloons [32]. Recently, SIRONA, a head-to-head randomized controlled, noninferiority study of a sirolimus- and paclitaxel-coated balloon in femoropopliteal disease, demonstrated noninferiority of sirolimus to paclitaxel in primary patency and composite freedom from CD-TLR, major target limb amputation and device- or procedure-related death [30]. The SirPAD randomized, controlled non-inferiority trial compared a sirolimus-coated balloon to uncoated-balloon in infrainguinal artery disease. The SirPAD trial demonstrated noninferiority and subsequent superiority with regard to major adverse limb events at 1 year [29]. These RCTs, along with real-world data from SUCCESS, suggest that sirolimus-coated balloons are a viable tool in the treatment of PAD.

Early studies evaluating the SELUTION SLR SEB demonstrated favorable outcomes in patients with femoropopliteal disease, but were generally limited by small sample sizes, less complex lesions, and predominantly claudicant populations. The first-in-human study reported a freedom from TLR rate at 98% at 6 months in relatively short lesions and limited chronic total occlusions [28]. The SELUTION SFA Japan study enrolled a larger cohort of claudicants with more complex femoropopliteal disease including longer lesion lengths and a high prevalence of severe calcification. The 12-month patency rate was 87.9% and TLR-free rate of 97.0% [24].

As stated previously, until this current study, the SELUTION SLR DEB has been mainly studied in claudicant populations with primarily SFA disease. More recently, small single-center registries have examined real-world use of the SELUTION SLR SEB in broader patient populations and lesion presentations such as CLTI and BTK disease. These studies have reported encouraging patency and TLR outcomes despite challenging lesion characteristics and low rates of bailout stenting [21, 23, 25]. The 91.1% freedom from CD-TLR through 12 months observed in the present study is in-line with prior studies, validating early promising results in a broader and larger population. Despite 98.9% lesion vessel preparation reported in the study, the majority was conducted with POBA. The bail-out stent rate was 32.0% in this study, which is not surprising given the median lesion length was 150 mm compared to 100 mm in the overall cohort. 42.1% of lesions reported CTOs and advanced vessel preparation techniques were not widely used. High bailout rates likely reflect lesion complexity rather than failure of the sirolimus technology itself. The benefits of advanced vessel preparation techniques in combination with a sirolimus-coated DEB remain an area of potential future exploration.

One of the benefits of the SUCCESS PTA study as an all-comers registry was that inclusion criteria allowed patients with a wide degree of symptomology and lesion complexity, including both (71.5%) claudicant and (28.5%) CLTI patients, as well as (81.0%) ATK and (19.0%) BTK lesions. The SUCCESS PTA study demonstrated an overall CD-TLR rate of 9.0% at 1 year. When outcomes were stratified by severity of symptoms at baseline, patients with claudication had a CD-TLR rate of 8.7%, whereas 10.4% was observed in the CLTI group. As expected, the major target limb amputation rate in the claudicants at 0% vs. 5.8% in those with CLTI.

Putting this data into context with other studies is challenging because the SUCCESS study included real-world patients within the full PAD spectrum (RC 1–6) and lesion location (ATK and BTK). The BIOLUX PIII study had a similar-sized patient population and wide inclusion criteria for both PAD presentation and anatomic lesion distribution. 700 patients were enrolled, of which 38% with CLTI and 12% with BTK disease. Lesion length, % of CTOs and incidence of severe calcium were 8.5 cm, 24% and 12% respectively. At 1 year, CD-TLR was similar to SUCCESS at 93.1% despite slightly less complex anatomy [33]. These outcomes are encouraging considering the inclusion of BTK arteries, whereas outcomes on BTK treatment with paclitaxel-coated DCBs are mixed, making it unclear if they benefit over POBA. 4 RCTs based on paclitaxel-coated DCBs failed to succeed with one of them raising a safety concern based on a trend towards a threefold higher amputation at 1 year [13–15, 34]. Only one RCT conducted in a Chinese population with more challenging vascular disease, longer lesions (17 cm) and higher CTO rate (75%) showed benefit of DCB vs. PTA [17].

There is very limited data on DCB treatment of isolated femoropopliteal disease in patients with CLTI to compare with the SUCCESS PTA study. Unlike SUCCESS, with a CLTI population that included 32.6% lesions BTK, The IN.PACT Global study only included CLTI patients with ATK lesions. Within that study, the freedom from CD-TLR was 86.3% in the CLTI group and rate of major target limb amputation was 1.4%. The authors concluded that the treatment of femoropopliteal disease with paclitaxel-coated DCB was safe in patients with CLTI [35]. Results from other ongoing randomized trials comparing limus DEBs to balloon angioplasty balloons (SELUTION4SFA-NCT05132361; SELUTION4BTK-NCT05055297; LIMES-NCT04772300) will help define the role of limus DEBs for treatment in the PAD population.

Limitations

The SUCCESS PTA Study is a single-arm study, limiting any comparison of the limus DEB with other treatments. Patency was not assessed in this study, which is thought to be a less biased endpoint as compared to freedom from CD-TLR. The registry was intentionally designed to capture contemporary treatment patterns without protocol-driven restrictions. One challenge of an all-comer registry with wide inclusion criteria is depending on the site and operating physician, there were a wide variety of choices available for vessel preparation. Vessel preparation has emerged as instrumental for definitive therapies to exert their full potential. This may be particularly true for DCBs as they miss the scaffolding property which allows stents to overcome elastic recoil. In addition to assigning highest recommendation for the use of DCBs as a definitive therapy in femoropopliteal PAD, a recent Delphi consensus highlighted the merits of multiple vessel prep modalities (particularly specialty balloons) as necessary to pave the ground for patency maintenance [32]. Moreover, the contribution of optimal vessel prep may be even more important in BTK arteries where an absolute lumen loss similar to fem-pop does pay a much higher penalty given the small caliper vessels involved. It may be speculated that a higher and systematic attention to vessel preparation and utilization of vessel preparation specialty devices beyond POBA may play a role in acute and long-term outcomes of this study, as well as past and future trials.

Guidelines for endovascular therapy in claudicant patients are often reserved for patients with disabling symptoms but not often recommended for Rutherford Class 1 or in claudicants with BTK lesions. 3.2% of the overall cohort was Rutherford Class (RC) 1, with 4.3% in the claudicant population. There were also patients that underwent BTK treatment with claudication. SUCCESS PTA did not include Rutherford Class as an exclusion criterion. Of the 3.2% of RC 1 patients in the overall cohort, all of those lesions had more than 50% stenosis and were enrolled per investigator discretion based on their site’s standard of care. BTK treatment with SELUTION was reported in 14.1% of claudicant populations (10.1% combined with ATK lesions, 4.0% isolated). It is recommended that treatment of isolated BTK lesions should be avoided [36]. The SUCCESS PTA study is about real-world patients treated per real practice, reflecting different institution or operators’ decisions and offers a reflection point on how guidelines or consensus documents are considered or not considered. The treatment of BTK stenoses in concomitance to an ATK lesion also calls for caution in a claudicant patient. However, the literature suggests that liberal BTK treatment practices still exist in some settings for claudicants as well [37].

Conclusion

The outcomes from this real-world single-arm study, which enrolled more complex patients, were consistent with similar paclitaxel-coated balloon registries and suggest this limus DEB platform may be an acceptable alternative to paclitaxel-coated balloons, especially in patients with CLTI.

Authors’ contributions

Conceptualization: ML, TZ, CR, AP, M.A. MedAlliance SA; methodology: ML, TZ, CR, AP, M.A. MedAlliance SA; investigation: all authors; data curation: ML, M.A. MedAlliance SA; formal analysis: all authors; validation: ML, TZ, CR, AP; resources: ML, M.A. MedAlliance SA; writing—original draft: ML, TZ, CR, AP, writing—review and editing: all authors.

Funding

This study was funded by M.A. MedAlliance SA.

Cordis

Data availability 

The datasets generated and/or analyzed during the current study contain patient information and are therefore not publicly available due to applicable data protection regulations and ethical restrictions.

Declarations

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Consent for publication

Consent for publication was obtained for every individual person’s data included in the study.

Competing interests

Michael Lichtenberg has served as consultant for MedAlliance, Cordis, BD BARD, Philips, Biotronik, Boston Scientific, Cagent, Shockwave, Cook Medical, Bayer Healthcare, Reflow Medical; Speakers’ Bureau for Medalliance, Cordis, BD BARD, Philips, Biotronik, Boston Scientific, Cagent, Shockwave, Cook Medical, Bayer Healthcare, Daiichi Sankyo, Reflow Medical.

Thomas Zeller has received honoraria from Acotec, BD Bard, Biotronik, Boston Scientific Corp., Cook Medical, Cordis, Medtronic, Veryan; he has consulted for: Boston Scientific Corp., Gore & Associates, Medtronic, Shockwave, VentureMed, Veryan and Reflow Medical; Institutional Grants for research have been received from: Acotec, Ablative Solutions, BD Bard Peripheral Vascular, Boston Scientific, Contego Medical, Cook Medical, Cordis, CSI, Gore & Associates, iVascular, MedAlliance, Medtronic, Micro Medical, R3 Vascular, Recor Medical, Reflow Medical, Reva Medical, Shockwave, Surmodics, Terumo, TriReme, University of Jena and he has ANT Stock options.

Ralph Kickuth has received speaking honoraria and travel support from Cordis and Becton Dickinson.

Konstantinos Katsanos has received honoraria from SIRTEX, Abbott Vascular, Cordis and Becton Dickinson; research grants from Cordis, he’s on an advisory board for SIRTEX and is Co-Director of AVA vascular meeting.

Stefan Müller-Hülsbeck is a consultant for Bayer and Terumo.

Grigorios Korosoglou has received speaker honoraria from Philips, Cordis, Boston Scientific and BARD Peripheral Vascular Inc., and institutional grants from Philips and Bard Peripheral Vascular Inc.

Christian Heiss is a member of the board of the European Society of Vascular Medicine and the chairperson elect of the nucleus of the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Disease. He has received research funding from the European Partnership on Metrology, co-financed from European Union’s Horizon Europe Research and Innovation Programme and UK Research and Innovation. He has received research funding to the institution from Medical Research Council, Lipton, iThera, and Ageless Science and honoraria for lectures by Bayer not related to the manuscript. He is a council member and president of the Royal Society of Medicine’s Vascular, Lipid and Metabolic Medicine Council.

Christos Rammos has received Honoraria from: Biotronik, BD Bard, Cordis, Daiichi-Sankyo, Inari, Novartis, Shockwave, Veryan; consulted for BD Bard, Boston Scientific Corp., Veryan, Shockwave and received Institutional Grants from: Biotronik, Boston Scientific Corp., Cook, Veryan, MedAlliance and Cordis.

Ashish Patel, Julio Andrés Pascua, Jörg Schmehl, Klaus Hertting, Ralph Oberacker, Aljoscha Rastan and Hans-Martin Gissler have no industry relationships related to the scope of this paper.