Clinical Comparison of Drug-Coated Balloon and Drug-Eluting Stent for Femoropopliteal Lesions in Chronic Limb-Threatening Ischemia With Wounds

Abstract

Background: Endovascular therapy (EVT) with devices such as drug-coated balloons (DCBs) and drug-eluting stents (DESs) for atherosclerotic disease in the femoropopliteal (FP) artery has been established. However, EVT using drug-based devices for chronic limb-threatening ischemia (CLTI) remains challenging. The optimal device for FP lesions in patients with CLTI remains unknown. This study compared the clinical efficacy of DCB and DES in patients with CLTI and FP lesions.

Methods and Results: This retrospective single-center study included 539 consecutive patients (562 lesions) treated with EVT between January 2018 and December 2022; 166 patients with CLTI and Rutherford Class 5 or 6 wounds underwent EVT with DCB or DES. Clinical outcomes were compared between 53 pairs after propensity score matching. There were no significant differences between the DCB and DES groups in the incidence of complete wound healing without death or major amputation (84.8% vs. 80.2%, respectively; P=0.99), primary patency (69.4% vs. 75.6%, respectively; P=0.65), and freedom from target lesion revascularization at 1 year (78.6% vs. 78.0%, respectively; P=0.92). Multivariate analysis showed that complete wound healing at 1 year is negatively associated with hemodialysis and Wound, Ischemia, and foot Infection Stage 4, but positively associated with Global Limb Anatomic Staging System FP Grade 3 or 4.

Conclusions: No significant differences in clinical outcomes were found between DCB and DES for patients with CLTI and FP lesions.

In the field of endovascular therapy (EVT), significant progress has been made with the development of paclitaxel-based devices that have improved patency rates for drug-eluting stents (DESs) and drug-coated balloons (DCBs).^1–3 DCBs and DESs generally use paclitaxel as an antiproliferative agent, which is known to significantly inhibit neointimal hyperplasia in the femoropopliteal (FP) artery. The clinical efficacy of EVT with drug-based devices such as DCBs or DESs in patients with FP lesions has been demonstrated in several clinical trials.^4–7 However, EVT for patients with chronic limb-threatening ischemia (CLTI) remains challenging, even with drug-based devices, because CLTI is a strong predictor of DCB or DES restenosis in FP lesions.^6,8,9 Thus, it is unclear which drug-based device would be more effective for patients with CLTI and FP lesions.

An advantage of DCBs over DESs in FP lesions is drug delivery to the arterial wall without a scaffold. Consequently, complications related to stent implantation, such as stent restenosis, stent fracture, and stent thrombosis, can be avoided.^10–13 Meanwhile, there is a concern that the use of DCBs in patients with CLTI can cause distal embolization during the procedure, resulting in lower extremity adverse events, including delayed wound healing and major amputation.¹⁴

Therefore, in this study, we sought to compare clinical outcomes between DCBs and DESs for FP lesions in patients with CLTI and wounds.

Methods

Study Population

This was a retrospective single-center observational study. Initially, 539 consecutive patients (562 lesions) with FP artery disease who underwent EVT at Miyazaki Medical Association Hospital between January 2018 and December 2022 were enrolled. Of these 539 patients (562 lesions), 323 patients (323 lesions) with Rutherford Class 2–4 disease and 50 patients (50 lesions) who were treated with other than drug-based devices were excluded. In addition, 23 lesions treated in the contralateral limb of the same patient were excluded. Ultimately, the study population consisted of 166 patients with CLTI (166 lesions) with Rutherford Class 5 or 6 disease who underwent EVT with a DCB (IN.PACT Admiral [Medtronic Vascular, Santa Clara, CA, USA], Lutonix [Becton Dickson and Company, Franklin Lakes, NJ, USA], or Ranger [Boston Scientific, Marlborough, MA, USA]) or a DES (Zilver PTX [Cook Medical, Bloomington, IN, USA] or Eluvia [Boston Scientific]; Figure 1). Follow-up information was obtained from hospital charts or by contacting patients or referring physicians. The median follow-up was 470 days (interquartile range 238–881 days).

Figure 1.

Study flowchart. DCB, drug-coated balloon; DES, drug-eluting stent; EVT, endovascular treatment.

This study was conducted in accordance with the tenets of the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of Miyazaki Medical Association Hospital (Approval no. 2023-43).

EVT Procedure

The ipsilateral or contralateral common femoral artery was selected as the approach site. In this study, the guiding sheath was 5 or 6 Fr. After insertion of the guiding sheath, 5,000 IU heparin was injected as a bolus, with 1,000 IU heparin injected every hour thereafter. We used a 0.014- or 0.018-inch guidewire. After the guidewire crossed the FP lesion, a balloon was inflated for at least 120 s. After balloon angioplasty, the DCB was inflated for 180 s or the DES was implanted. After DES implantation, post-dilation was performed for at least 30 s. The length and size of the balloon and the selection of drug-based device (DCB or DES) were left to the discretion of each operator. All patients were advised to continue low-dose aspirin therapy (81–162 mg/day), in addition to a P2Y₁₂ inhibitor (75 mg clopidogrel daily or 3.75 mg prasugrel daily) for a minimum of 1 month after EVT.

Quantitative Vascular Angiography Analysis

Quantitative vascular angiography analysis was performed at baseline and after EVT using an automated edge detection system (CAAS 5.9; Pie Medical Imaging BV, Maastricht, Netherlands). Analyses were performed by 2 experienced observers (K.N. and K.Y.) who were blinded to patient characteristics.

Definitions

Procedural success was defined as residual stenosis of <30% without flow limitations. The primary outcome of the study was complete wound healing, defined as complete epidermalization of all wounds without death or major amputation. We also evaluated primary patency, freedom from target lesion revascularization (TLR), overall survival, and limb salvage. Primary patency was defined as the absence of restenosis and TLR. Restenosis was defined as a peak systolic velocity ratio >2.4 or occlusion observed on duplex ultrasound, or >50% diameter stenosis or occlusion on follow-up angiography. TLR was defined as the need for revascularization. Limb salvage was defined as the avoidance of amputation above the ankle. The degree of lesion calcification on angiography was assessed using the Peripheral Arterial Calcification Scoring System (PACSS).¹⁵ The degree of vessel dissection was based on the criteria for coronary artery dissection, with 6 grades of dissection (A–F), as reported previously.¹⁶

Non-ambulatory status was defined as wheelchair use or being bedridden on admission. Risk factors for cardiovascular disease included hypertension (>140/90 mmHg or the use of antihypertensive medications), dyslipidemia (high-density lipoprotein cholesterol <40 mg/dL, low-density lipoprotein cholesterol ≥140 mg/dL, or the use of lipid-lowering medications), and diabetes (fasting plasma glucose ≥126 mg/dL, 2-h plasma glucose after an oral glucose tolerance test ≥200 mg/dL, HbA1c ≥6.5%, or the use of medications for diabetes). Hypoalbuminemia was defined as the first serum albumin value <3.0 g/dL on admission.^17,18 Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m² on admission. The Wound, Ischemia, and foot Infection (WIfI)¹⁹ classification was used to estimate 1-year amputation risk; it was determined retrospectively using medical records such as photographs of the foot and laboratory data on admission. The Global Limb Anatomic Staging System (GLASS)²⁰ was used to estimate preprocedural anatomical complexity.

Follow-up Assessment

After discharge, patients were followed up by attending physicians in an outpatient setting. Follow-up intervals and methods were left to the discretion of the attending physician. Typically, patients were seen every 2–4 weeks until the wound healed. TLR was clinically indicated in patients with delayed wound healing or restenosis diagnosed with duplex ultrasound.

Statistical Analysis

To avoid the potential effects of a non-randomized study design, a propensity score was calculated using a multivariate logistic regression model with DCB or DES as the dependent variable. Continuous variables are expressed as the mean±SD or the median with interquartile range, as appropriate. Categorical variables are presented as numbers and percentages. Wound healing without death or major amputation, primary patency, TLR, overall survival, and limb salvage were assessed using the Kaplan-Meier method; differences were evaluated using the log-rank test. A multivariable Cox proportional hazards model was used to identify predictors of 1-year amputation-free survival with adjustment for variables with P<0.05 in a univariate analysis. Results are expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). All statistical analyses were performed using SPSS version 19 (IBM Corp., Somers, NY, USA). All tests were 2-tailed. P<0.05 was considered statistically significant.

Results

Patient and Lesion Characteristics

Of the 166 patients, 102 were classified into the DCB group and 64 patients were classified into the DES group. Patient characteristics are presented in Table 1. Compared with the DCB group, the DES group had a lower ankle-brachial index (ABI), a higher prevalence of advanced GLASS FP grade, a smaller percentage diameter stenosis, and a larger reference diameter. WIfI clinical stage did not differ between the 2 groups.

Table 1.

Patient and Lesion Characteristics Before and After Propensity Score Matching

	Before matching			After matching
	DCB (n=102)	DES (n=64)	P value	DCB (n=53)	DES (n=53)	P value
Age (years)	75.8±10.5	75.5±10.0	0.82	76.2±10.1	74.9±10.4	0.53
Male sex	61 (59.8)	34 (53.1)	0.42	34 (64.2)	27 (51.0)	0.24
Non-ambulatory	54 (52.9)	37 (57.8)	0.63	29 (54.7)	29 (54.7)	1.00
Hypertension	93 (90.3)	60 (93.8)	0.77	47 (88.7)	50 (94.3)	0.49
Dyslipidemia	62 (60.8)	41 (64.1)	0.74	29 (54.7)	34 (64.2)	0.43
Diabetic	68 (66.7)	46 (71.9)	0.50	30 (56.6)	38 (71.7)	0.16
Smoking	48 (47.1)	30 (46.9)	1.00	26 (49.1)	23 (43.4)	0.70
CKD	81 (79.4)	47 (73.4)	0.45	40 (75.5)	40 (75.5)	1.00
Hemodialysis	49 (47.1)	25 (39.1)	0.27	22 (41.5)	22 (41.5)	1.00
Albumin (g/dL)	3.45±0.55	3.50±0.71	0.56	3.44±0.58	3.56±0.72	0.35
Hypoalbuminemia	15 (14.7)	14 (21.9)	0.29	8 (15.1)	10 (18.9)	0.80
Chronic heart failure	34 (33.3)	15 (23.4)	0.22	16 (30.2)	14 (26.4)	0.83
EF (%)	55.9±13.2	57.0±12.0	0.57	55.4±13.5	56.8±12.4	0.58
Ischemic heart disease	45 (44.1)	23 (35.9)	0.33	19 (35.8)	20 (37.7)	1.00
Atrial fibrillation	18 (17.6)	5 (7.8)	0.11	11 (20.8)	5 (9.4)	0.17
Cerebral infarction	17 (16.7)	9 (14.1)	0.83	12 (22.6)	10 (18.9)
Aspirin	86 (84.3)	56 (87.5)	0.65	45 (84.9)	45 (84.9)	1.00
P2Y12 inhibitor	95 (93.1)	61 (95.3)	0.74	51 (96.2)	50 (94.3)	1.00
Cilostazol	8 (7.8)	7 (10.9)	0.58	5 (9.4)	7 (13.2)	0.76
Warfarin	4 (3.9)	7 (10.9)	0.11	2 (3.8)	5 (9.4)	0.44
DOAC	15 (14.7)	5 (7.8)	0.23	8 (15.1)	5 (9.4)	0.56
RAS inhibitor	45 (44.1)	33 (51.6)	0.43	21 (39.6)	28 (52.8)	0.24
Statin	62 (60.8)	43 (67.2)	0.51	32 (60.3)	38 (71.7)	0.31
Insulin	29 (28.4)	18 (28.1)	1.00	13 (24.5)	18 (34.0)	0.39
Rutherford class			0.20			0.78
5	88 (86.3)	50 (78.1)		46 (86.8)	44 (83.0)
6	14 (13.7)	14 (21.9)		7 (13.2)	9 (17.0)
CRP (mg/dL)	2.14±3.47	2.86±4.33	0.24	2.39±4.16	2.67±4.20	0.73
WIfI clinical stage			0.88			0.66
1	17 (16.7)	10 (15.6)		6 (11.3)	10 (18.9)
2	17 (16.7)	8 (12.5)		10 (18.9)	8 (15.1)
3	40 (39.2)	28 (43.8)		22 (41.5)	23 (43.4)
4	28 (27.4)	18 (28.1)		15 (28.3)	12 (22.6)
GLASS FP grade			0.003			0.44
1	11 (10.8)	3 (4.7)		7 (13.2)	3 (5.7)
2	25 (24.5)	14 (21.9)		9 (17.0)	12 (22.6)
3	45 (44.1)	17 (26.6)		20 (37.7)	17 (32.1)
4	21 (20.6)	30 (46.9)		17 (32.1)	21 (39.6)
GLASS IP grade			0.24			0.24
0	13 (12.7)	7 (10.9)		9 (17.0)	6 (11.3)
1	7 (6.9)	3 (4.7)		4 (7.5)	2 (3.8)
2	10 (9.8)	3 (4.7)		6 (11.3)	2 (3.8)
3	14 (13.7)	4 (6.3)		5 (9.4)	3 (5.7)
4	58 (56.9)	47 (73.4)		29 (54.7)	40 (75.5)
Infrainguinal GLASS stage			0.07			0.35
1	4 (3.9)	1 (1.6)		3 (5.7)	1 (1.9)
2	18 (17.6)	4 (6.3)		7 (13.2)	4 (7.5)
3	80 (78.4)	59 (92.2)		43 (81.1)	48 (90.1)
GLASS inframalleolar grade			0.17			0.40
P0	13 (12.7)	9 (14.1)		11 (20.8)	8 (15.1)
P1	68 (66.7)	34 (53.2)		30 (56.7)	27 (50.9)
P2	21 (20.6)	21 (32.8)		12 (22.6)	18 (34.0)
PACSS grade			0.76			0.86
0	25 (24.5)	16 (25)		16 (30.2)	12 (22.6)
1	12 (11.8)	10 (15.6)		6 (11.3)	8 (15.1)
2	17 (16.7)	14 (21.9)		9 (17.0)	12 (22.6)
3	27 (26.5)	13 (20.3)		12 (22.6)	12 (22.6)
4	21 (20.6)	11 (17.2)		10 (18.9)	9 (17.0)
History of treatment for aortoiliac lesions	28 (27.5)	11 (17.2)	0.14	11 (20.8)	11 (20.8)	1.00
Including popliteal artery	70 (68.6)	40 (62.5)	0.50	37 (69.8)	33 (62.3)	0.54
Previous ABI	0.48±0.29	0.37±0.26	0.015	0.43±0.30	0.38±0.26	0.36
Pre %DS (%)	86.6±11.1	95.1±7.6	<0.001	91.9±9.0	93.9±8.0	0.23
Reference vessel diameter (mm)	5.17±0.67	5.47±0.56	0.002	5.40±0.64	5.40±0.58	0.96
Lesion length (cm)	24.4±10.4	26.4±9.8	0.22	25.1±11.1	25.6±9.7	0.79
Drug device
IN.PACT Admiral	31 (30.4)	–	–	16 (30.2)	–	–
Ranger	43 (42.1)	–	–	25 (47.2)	–	–
Lutonix	28 (27.5)	–	–	12 (22.6)	–	–
Zilver PTX	–	21 (32.8)	–	–	20 (37.7)	–
Eluvia	–	43 (67.2)	–	–	33 (62.3)	–

Unless indicated otherwise, values are presented as the mean±SD or n (%). %DS, percentage diameter stenosis; ABI, ankle-brachial index; CKD, chronic kidney disease; CRP, C-reactive protein; DCB, drug-coated balloon; DES, drug-eluting stent; DOAC, direct oral anticoagulant; EF, ejection fraction; FP, femoropopliteal; GLASS, Global Limb Anatomic Staging System; IP, infrapopliteal; PACSS, Peripheral Arterial Calcification Scoring System; RAS, renin-angiotensin system; WIfI, Wound, Ischemia, and foot Infection.

Because of significant differences in patient and lesion characteristics between the 2 groups, propensity score matching was performed before comparing clinical outcomes. After matching, 53 matched pairs of patients were included in the analysis; patient and lesion characteristics were comparable between the 2 groups (Table 1).

Procedural Characteristics

The procedural characteristics after matching are presented in Table 2. Compared with the DES group, rates of scoring balloon use and chocolate balloon use were higher in the DCB than DES group (43.4% vs. 17.0% [P=0.048] and 18.9% vs. 1.9% [P=0.008], respectively). The rate of high-pressure balloon use was lower in the DCB than DES group (67.9% vs. 92.5%, respectively; P=0.003). No patients in the DCB group required provisional stenting. Intravascular ultrasound (IVUS)-guided EVT was performed in most patients in both groups (96.2% vs. 96.2% in the DCB and DES groups, respectively; P=1.00). The slow-flow phenomenon was observed in 17.0% of patients in the DCB group, but was not observed in the DES group (P=0.003). Severe vascular dissection (Type ≥C) was not observed in the DES group, but was observed in 20.8% of patients in the DCB group (P<0.001). In the DES group, 24.5% of patients were treated with additional DCBs for lesions more distal to the DES site, but the mean length of lesions treated with additional DCBs was much shorter than the mean length of lesions treated with DES (252.1±107.6 vs. 53.85±12.60 mm, respectively). The DCB group had a larger post-procedure percentage diameter stenosis than the DES group (19.3±9.6% vs. 3.5±5.7%, respectively; P<0.001), but post-procedure ABI and the incidence of procedural success were similar between the DCB and DES groups (0.87±0.20 vs. 0.91±0.19 [P=0.38] and 96.2% vs. 100% [P=0.50], respectively; Table 2).

Table 2.

Procedural Characteristics

	DCB (n=53)	DES (n=53)	P value
Use of scoring balloon	23 (43.4)	9 (17.0)	0.048
Use of chocolate balloon	10 (18.9)	1 (1.9)	0.008
Use of high-pressure balloon	36 (67.9)	49 (92.5)	0.003
DCB diameter (mm)	5.85±0.63	–	–
DCB length (mm)	281.7±128.5	–	–
No. DCBs	1.92±0.73	–	–
DES diameter (mm)	–	6.70±0.46	–
DES length (mm)	–	252.1±107.6	–
No. DESs	–	2.06±0.84	–
Additional DCB	–	13 (24.5)	–
No. additional DCBs	–	1.00	–
Additional DCB diameter (mm)	–	5.69±0.63	–
Additional DCB length (mm)		53.85±12.60
Provisional stenting	0 (0)	–	–
IVUS use	51 (96.2)	51 (96.2)	1.00
Slow-flow phenomenon (TIMI Grade ≤2)	9 (17.0)	0 (0)	0.003
Additional treatment for below-knee arteries	35 (66.0)	41 (77.4)	0.28
Dissection type			<0.001
None	23 (43.4)	53 (100)
A	10 (18.9)	0 (0)
B	9 (17.0)	0 (0)
C	8 (15.1)	0 (0)
D	3 (5.7)	0 (0)
E and F	0 (0)	0 (0)
Procedural complications	5 (9.4)	7 (13.2)	0.76
Pseudoaneurysm	0 (0)	2 (3.8)	0.50
Hematoma	4 (7.5)	4 (7.5)	1.00
Arteriovenous fistula	0 (0)	0 (0)	1.00
Wire perforation	0 (0)	0 (0)	1.00
Transfusion	5 (9.4)	5 (9.4)	1.00
Post-procedural %DS (%)	19.3±9.6	3.5±5.7	<0.001
Residual stenosis ≤30%	51 (96.2)	53 (100)	0.50
Procedural success	51 (96.2)	53 (100)	0.50
Post-procedural ABI	0.87±0.20	0.91±0.19	0.38

Unless indicated otherwise, values are presented as the mean±SD or n (%). IVUS, intravascular ultrasound; TIMI, Thrombolysis in Myocardial Infarction. Other abbreviations as in Table 1.

Clinical Outcomes at 1 Year

Complete wound healing rates at 1 year were similar between the DCB and DES groups (84.8% vs. 80.2%, respectively; P=0.99; Figure 2). No significant differences were found between the DCB and DES groups in primary patency (69.4% vs. 75.6%, respectively; P=0.65) or freedom from TLR (78.6% vs. 78.0%, respectively; P=0.92; Figure 3). Overall survival and limb salvage rates at 1 year were also comparable in the DCB and DES groups (87.2% vs. 91.8% [P=0.45] and 91.5% vs. 87.8% [P=0.86], respectively; Figure 3).

Figure 2.

Kaplan-Meier curves for wound healing without death or major amputation. DCB, drug-coated balloon; DES, drug-eluting stent.

Figure 3.

Kaplan-Meier curves for primary patency, freedom from target lesion revascularization, overall survival, and limb salvage. DCB, drug-coated balloon; DES, drug-eluting stent.

Multivariate Cox proportional hazards analysis showed that hemodialysis (HR 0.38; 95% CI 0.14–0.99) and WIfI Stage 4 (HR 0.19; 95% CI 0.07–0.56) are negatively associated with complete wound healing and that GLASS FP Grade 3 or 4 (HR 3.10; 95% CI, 1.12–8.58) is associated with complete wound healing (Table 3). In addition, there were no differences in the complete wound healing rate between the 2 groups.

Table 3.

Cox Proportional Hazards Analysis of 1-Year Wound Healing Without Death or Major Amputation

	Unadjusted analysis			Adjusted analysis
	HR	95% CI	P value	HR	95% CI	P value
Age	0.98	0.94–1.02	0.31
Male sex	2.07	0.92–4.66	0.10
Non-ambulatory	0.78	0.34–1.79	0.68
Diabetes	0.80	0.34–1.89	0.67
Hemodialysis	0.35	0.15–0.81	0.02	0.38	0.14–0.99	0.048
Hypoalbuminemia	0.40	0.14–1.12	0.097	0.58	0.17–1.94	0.58
EF (per 10% increase)	1.18	0.86–1.61	0.31
Cilostazol	1.48	0.37–5.84	0.75
Statin	2.31	0.99–5.40	0.08	1.78	0.66–4.85	0.26
Rutherford Class 6	0.41	0.14–1.20	0.14
WIfI Stage 4	0.16	0.06–0.42	<0.001	0.19	0.07–0.56	0.003
CRP (per 1-mg/dL increase)	1.00	0.91–1.10	0.94
GLASS FP Grade 3 or 4	2.76	1.15–6.63	0.025	3.10	1.12–8.58	0.03
GLASS IP Grade 3 or 4	0.46	0.17–1.26	0.16
Infrainguinal GLASS Stage 3	0.74	0.22–2.52	0.77
GLASS inframalleolar Grade P2	0.66	0.27–1.62	0.36
PACSS Grade 4	0.77	0.27–2.18	0.60
IVUS use	2.19	0.30–16.23	0.59
Use of DCB (vs. DES)	0.59	0.26–1.35	0.30
Slow-flow phenomenon	0.94	0.22–4.00	1.00
Popliteal artery involvement	0.90	0.38–2.14	1.00

CI, confidence interval; CTO, chronic total occlusion; HR, hazard ratio; TASC, Transatlantic Society Consensus. Other abbreviations as in Tables 1,2.

Discussion

The main findings of this study were that: (1) complete wound healing, primary patency, freedom from TLR, overall survival, and limb salvage rates are similar for the DCB and DES strategies used to treat FP lesions in CLTI with wounds; and (2) WIfI Stage 4 and hemodialysis are negatively associated with complete wound healing, whereas GLASS FP Grade 3 or 4 is positively associated with complete wound healing. This is the first report to compare the clinical outcomes of DCB and DES intervention for FP lesions in patients with CLTI.

CLTI is the end stage of lower extremity artery disease, a condition with poor prognosis for survival as well as major amputation. In addition, the incidence of major amputation in the first year after diagnosis is approximately 25% without an adequate revascularization procedure.²¹ Currently, EVT is used frequently as the first revascularization strategy. This shift is largely attributed to advancements in medical devices, particularly for FP interventions, where drug technology has made significant progress.^1–3 The use of DCBs or DESs for FP lesions is increasingly common in our daily practice. In real-world practice, the clinical utility of DCB and DES intervention has been established in several clinical trials.^4–7 However, EVT using drug-based devices for patients with CLTI remains challenging because CLTI is a predictor of restenosis.^6,8,9 The clinical outcomes of DCB and DES intervention in patients with CLTI have been reported,^22,23 but it is unclear which device is more effective in daily practice.

The utility of EVT with a DCB for FP lesions in patients with CLTI has been shown in several clinical trials.²³ The advantage of EVT with a DCB is that it leaves nothing in the vessel wall and avoids stent-related complications in the chronic phase while still achieving acceptable results.^10–13 Conversely, the advantage of DESs compared with DCBs is the scaffolding for FP lesions, which supports the vessel wall due to its metallic structure. This support helps keep the artery open and prevents elastic recoil of the vessel after the procedure. Several studies have demonstrated the utility of a DES-based strategy for patients with CLTI.^4,6 They have also shown that, compared with DCBs, DESs are more commonly chosen for patients with complex lesions in real-world practice.⁶ Indeed, the DES group in the present study had more complex lesions and a lower ABI than the DCB group before propensity score matching. However, DES use raises concerns about complications related to DES implantation, such as stent restenosis, stent occlusion, stent fracture, and stent thrombosis.^10–13 Therefore, there is no definitive consensus on whether DCB or DES is more effective in patients with CLTI.

In this study, the rate of wound healing without death or major amputation in patients with CLTI was similar in the 2 groups. This result may be explained by the similarity in primary patency and TLR rates between the 2 groups. Previous randomized control trials evaluating DCB and DES, REAL PTX and DRug-eluting bAlloon verSus drug-eluTIng stent for COmplex Femoropopliteal Arterial Lesions (DRASTICO),^24,25 showed no significant differences in clinical outcomes, including primary patency and TLR rates, at 1 year. Our results support these previous findings. In the present study, the bailout stenting rate was 0%, whereas in previous studies the rate was 20–25%.^24,25 This may be because of the greater use of chocolate and scoring balloons in the DCB than in the DES group, thus avoiding severe dissections.^26,27 In addition, to obtain larger area for FP lesions, the balloon size used in the present study was larger than the reference vessel diameter, as measured by quantitative vascular angiography, because the balloon size in this study was often matched to the external elastic membrane diameter, as measured with IVUS. DCB strategies tailored to the external elastic membrane diameter measured with IVUS are considered to be more effective than DCB strategies.^28,29 As a result, even in the DCB group, we were able to achieve acceptable lumen area and reduce the number of severe vessel dissections, which affects vessel patency. In this study, the rates of primary patency and freedom from TLR at 1 year in the DCB and DES groups were lower than reported in previous studies.^24,25 This may be mainly due to the fact that the present study included only patients with CLTI who had Rutherford Class 5 or 6 disease. In addition, lesions were longer and the percentage of patients on dialysis was higher than in previous studies. Moreover, using DCB for patients with CLTI raises concerns about distal embolization. However, Hata et al. reported that EVT with DCB did not affect wound healing, mortality, or major amputation rates.³⁰ In the present study, the slow-flow phenomenon occurred more frequently in the DCB than DES group. Nonetheless, no significant differences in the wound healing rate at 1 year were observed between the 2 groups. The slow-flow phenomenon was not associated with complete wound healing. Based on our results, when less dissection and an acceptable lumen area are achieved with optimal lesion preparation, even for patients with CLTI, the DCB strategy is reasonable.

This study showed that hemodialysis and WIfI Stage 4 are negative predictors of complete wound healing, which is consistent with previous reports.^20,31,32 Even with highly developed devices for FP lesions, complete wound healing may remain highly dependent on patient characteristics. In contrast, EVT for GLASS FP Grade 3 or 4 lesions was associated with complete wound healing. GLASS FP Grade 3 or 4 lesions had more occlusion and were longer and more involved with the popliteal lesion. Therefore, revascularization for such lesions using DCB or DES was more effective than for GLASS FP Grade 1 or 2 lesions and led to better wound healing for CLTI with wounds.³³

Study Limitations

This study has several limitations. First, this was a retrospective observational single-center study with a small number of participants. Therefore, selection bias and unmeasured confounding may have occurred. Second, severe dissection or significant residual stenosis after balloon angioplasty for preparation is more likely to be associated with DES implantation and likely leads to selection bias by the operator. Third, this study did not evaluate clinical outcomes for each type of DCB or DES. Future prospective studies with larger numbers of patients are needed to confirm these findings. Finally, 24.5% of the patients in the DES group underwent combination therapy involving DES and DCB, which may have influenced the outcomes.

Conclusions

The combination of optimal lesion preparation and DCB can bring clinical outcomes equal to DES in terms of wound healing without death or major amputation, primary patency, and freedom from TLR for patients with CLTI and wounds.

Acknowledgments

The authors are grateful to the staff of Miyazaki Medical Association Hospital.

Disclosures

K.T. is a member of Circulation Journal’s Editorial Team. The remaining authors have no conflicts of interest to declare.

IRB Information

This study was approved by the Ethics Committee of Miyazaki Medical Association Hospital (Reference no. 2023-43).

Data Availability

The deidentified participant data will not be shared.

References

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