Patterns and Timings of Recurrence After Fluoropolymer-Coated Drug-Eluting Stent Use for Femoropopliteal Artery Diseases　― Results of the PLANET Study ―

Abstract

Background: Fluoropolymer-coated drug-eluting stents (FP-DESs) are widely used to treat femoropopliteal artery (FPA) disease. However, data on the pattern and timing of recurrence after FP-DES implantation are limited. This study aimed to address this knowledge gap.

Methods and Results: This multicenter retrospective study analyzed 439 limbs of 398 patients treated with FP-DESs for de novo FPA lesions. The outcome measures were clinical outcomes in cases of recurrence, defined as a composite of restenosis and reocclusion. The timing of recurrence was categorized into early (within 1 year of treatment) and late (after 1 year). The factors associated with recurrence were analyzed by comparing cases of early and late recurrence. The early recurrence group showed a significantly higher frequency of reocclusion, particularly stent thrombosis. In addition, in this group, patients with reocclusion tended to exhibit significantly more severe clinical symptoms than those with restenosis. Deployment of FP-DES beyond the P1 segment was independently associated with early recurrence. Chronic total occlusion was independently associated with early reocclusion. Female sex, diabetes, not using statins, and long lesions were independently associated with late recurrence. Not using statins, warfarin use, and long lesions were independent predictive factors for late reocclusion.

Conclusions: The patterns and clinical symptoms of recurrence after FP-DES implantation for FPA differed according to the timing of recurrence, as did the factors associated with recurrence.

The incidence of symptomatic lower-extremity peripheral artery disease (PAD) has recently increased with global population aging.^1,2 Drug-eluting technology using endovascular therapy (EVT) devices is an established, effective modality for femoropopliteal artery (FPA) disease^3–5 and has been recommended as the first-choice strategy in recent guidelines.⁶ In particular, fluoropolymer-coated drug-eluting stents (FP-DESs) have demonstrated effective clinical performance in real-world settings.^7,8 Recent guidelines have recommended their use over drug-coated balloons (DCBs) when vessel preparation is suboptimal.⁹ FP-DES is a scaffold designed to enable the sustained release of paclitaxel by incorporating a polymer. The drug-elution period is approximately 1 year,³ which is the cut-off point for the high incidence of recurrence after stent placement in FPA lesions.¹⁰ FP-DES is said to have a low recurrence rate, although when recurrence occurs, it typically presents with an occlusive pattern.^7,11 However, data on recurrences within 1 year (when drug elution is presumed to be active) and beyond 1 year remain limited. Hence, the aim of the present study was to examine the patterns and timing of recurrence after FP-DES placement, clinical symptoms, rate of subsequent reintervention, and factors associated with early and late recurrence.

Methods

Study Design and Population

The clinical investigation of recurrence patterns and timing after placement of an FP-DES for FPA lesions (PLANET study) included patients with PAD who underwent EVT between January 2019 and December 2022. Data were retrieved from the LEADers PAD registry database, a retrospective multicenter registry (8 Japanese institutions) of lower-extremity PAD. The inclusion criteria were age ≥20 years, symptomatic lower limb ischemia, stenotic or occlusive de novo lesions in the FPA, and treatment with the Eluvia DES (Boston Scientific, Marlborough, MA, USA). Patients who underwent treatment involving a combination of DCBs and other scaffolding devices, including bailout stenting, were excluded from the study. In total, 439 limbs of 398 patients were analyzed. Recurrence timing was categorized into early (within 1 year of treatment) and late (after 1 year).

This study was approved by the Medical Ethics Committee of Ogaki Municipal Hospital (Approval no. 20240425-2) and the ethics committee of each participating hospital. The study was conducted in accordance with the Declaration of Helsinki. Owing to the retrospective observational nature of the study, the requirement for informed consent was waived. However, patients were able to opt out of the study. Relevant information regarding the study is available to the public in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects.

Outcome Measures

The outcome measures were clinical outcomes in cases of recurrence, including recurrence patterns, clinical symptoms, and the incidence of subsequent target lesion revascularization (TLR). Moreover, patients with recurrence without TLR were divided into the following 2 groups according to the reason for not performing TLR: (1) no TLR needed (i.e., physicians determined that TLR was not necessary either because the patient was asymptomatic or showed improvement from baseline status); and (2) TLR needed but not performed (i.e., physicians deemed TLR necessary but it was not performed either because the patient refused or at the physician’s discretion). The factors associated with recurrence were also analyzed by comparing the early and late recurrence groups.

Definitions and Data Collection

Angiographic data were analyzed at each institution according to a consensus between 2 experienced vascular interventionists. The severity of lesion calcification was evaluated using the 5-point Peripheral Arterial Calcium Scoring System (0–4).¹² Recurrence was defined as a composite of restenosis (indicated by a peak systolic velocity ratio >2.4 on duplex ultrasound or >50% stenosis on angiography or computed tomography)¹³ and reocclusion. To assess recurrence patterns, reocclusion was further classified as non-thrombotic reocclusion or stent thrombosis. Stent thrombosis was defined as reocclusion that met the following criteria: (1) initial procedural success; (2) rapid symptom occurrence; (3) thrombus present during the procedure; and (4) lesion resolution with <50% narrowing of the diameter by thrombolysis therapy.¹⁴ TLR was defined as reintervention within 5 mm proximal or distal to the original treatment segment for >50% stenosis, identified by duplex ultrasound or angiography, with recurrent clinical symptoms.^3,15

Medication and Procedural Protocol

Drugs were administered before and after EVT, according to local hospital policies and at the discretion of the attending physician. Antiplatelet therapy included aspirin, clopidogrel, and prasugrel. Dual antiplatelet therapy, consisting of aspirin and thienopyridine, was administered. Warfarin or a direct oral anticoagulant (dabigatran, edoxaban, apixaban, or rivaroxaban) was administered as anticoagulant therapy. The operator determined the access site and device according to the EVT procedure. After sheath placement, an intra-arterial or intravenous heparin bolus was administered as an anticoagulation treatment during EVT in all cases. The heparin dose was adjusted to achieve an activated clotting time of 200–300 s, following the hospital policy and at the operator’s discretion. The choice of EVT device was left to the discretion of the operator and depended on factors such as patient background, lesion characteristics, and interventional results.

Follow-up Protocol

Clinical investigations were routinely performed at baseline, 1, 3, 6, and 12 months after the procedure, and thereafter every 6 months, regardless of ischemic symptoms. The patency of the target lesion was assessed using both the ankle-brachial index and duplex ultrasound. Imaging investigations using computed tomography or angiography were performed as needed.

Statistical Analysis

To evaluate baseline clinical characteristics, continuous variables are expressed as the mean±SD or as the median with interquartile range (IQR). Categorical variables are expressed as numbers and percentages. Comparisons of recurrence patterns, clinical symptoms, and TLR rates were performed using the Chi-squared test. Kaplan-Meier analysis of recurrence and reocclusion was also performed. Cox regression analysis was performed to identify factors independently associated with recurrence after FP-DES treatment. Variables significantly associated with recurrence (P<0.05) in the univariate analyses were introduced into the multivariable Cox model. The results are reported as adjusted hazard ratios with corresponding 95% confidence intervals. All statistical analyses were performed using SPSS version 27 (IBM Corp., Armonk, NY, USA). All P values were 2-tailed, and P<0.05 was considered significant.

Results

Patient Characteristics

The mean patient age was 74.5±9.3 years, and 71.4% of the study participants were male. Diabetes and hemodialysis were present in 57.8% and 28.9% of patients, respectively. Patient characteristics are summarized in Table 1.

Table 1.

Baseline Clinical Characteristics

Patient characteristics (n=398)
Age (years)	74.5±9.3
Male sex	284 (71.4)
Body mass index (kg/m2)	21.9 [19.9–24.3]
Diabetes	230 (57.8)
Hypertension	840 (85.4)
Dyslipidemia	258 (64.8)
Current smoker	98 (24.6)
Coronary artery disease	178 (44.7)
Cerebrovascular disorder	64 (16.1)
Hemodialysis	115 (28.9)
Atrial fibrillation	64 (16.1)
Aspirin use	325 (81.7)
Thienopyridine use	358 (89.9)
DAPT use	291 (73.1)
Cilostazol use	49 (12.3)
Warfarin use	24 (6.0)
DOAC use	54 (13.6)
Statin use	257 (64.6)
Lesion characteristics (n=439)
CLTI	163 (37.1)
Preprocedural ABI	0.55±0.26
SFA	438 (99.8)
POPA	106 (24.1)
Lesion length (mm)	204.2±97.6
Chronic total occlusion	268 (61.0)
PACSS classification
Grade 0	173 (39.4)
Grade 1	52 (11.8)
Grade 2	40 (9.1)
Grade 3	67 (15.3)
Grade 4	107 (24.4)
PACSS 3/4	174 (39.6)
Proximal RVD (mm)	6.3±0.9
Distal RVD (mm)	5.9±1.0
Below-the-knee run-off
No run-off	22 (5.0)
1 run-off	139 (31.7)
2 run-offs	204 (46.5)
3 run-offs	74 (16.9)
Poor run-off (0/1)	161 (36.7)
Procedural characteristics (n=439 lesions)
Main access site
Ipsilateral FA	192 (43.7)
Contralateral FA	243 (55.4)
Trans-ankle	4 (0.9)
Retrograde approach	89 (20.4)
Predilatation	421 (95.9)
Pre-balloon diameter (mm)	5.5±0.9
Post-dilatation	427 (97.3)
Post-balloon diameter (mm)	5.9±0.8
Maximum DES diameter (mm)	6.6±0.5
Minimum DES diameter (mm)	6.4±0.5
No. DES deployed
1	123 (28.0)
2	127 (28.9)
3	189 (43.1)
Total DES length (mm)	224.9±102.6
IVUS use	389 (88.6)
Spot stenting	21 (4.8)
Stent beyond P1 segment	37 (8.5)

Values are given as n (%), mean±SD, or median [interquartile range]. ABI, ankle-brachial index; CLTI, chronic limb-threatening ischemia; DAPT, dual antiplatelet therapy; DES, drug-eluting stent; DOAC, direct oral anti-coagulants; FA, femoral artery; IVUS, intravascular ultrasound; PACSS, Peripheral Arterial Calcium Scoring System; POPA, popliteal artery; RVD, reference vessel diameter; SFA, superficial femoral artery.

Lesion and Procedural Characteristics

Table 1 presents details of the lesions and their procedural characteristics. Approximately 40% of limbs presented with chronic limb-threatening ischemia. The mean lesion length was 204.2±97.6 mm, and reference vessel diameter was 6.3±0.9 mm (proximal) and 5.9±1.0 mm (distal). The frequencies of chronic total occlusion (CTO) and bilateral wall calcification were 61.0% and 39.6%, respectively. Spot stenting and stent deployment beyond the P1 segment were performed in 4.8% and 8.5% of lesions, respectively.

Recurrence Patterns

The median follow-up duration was 852 days (IQR 455–1,287 days). Recurrence occurred in 98 lesions during the study period. Early recurrence occurred in 36 lesions (8 with restenosis and 28 with reocclusion), whereas late recurrence occurred in 62 lesions (31 with restenosis and 31 with reocclusion). Reocclusion was more common than restenosis throughout the study (Figure 1), with the early recurrence group showing a significantly higher frequency of reocclusion, particularly stent thrombosis, than the late recurrence group (52.8% vs. 14.5%; P<0.001). Kaplan-Meier analysis of recurrence and reocclusion is presented in the Supplementary Figure. The Kaplan-Meier estimated recurrence rate at 3 years was 30.4%, whereas the estimated reocclusion rate was 19.3%.

Figure 1.

Recurrence patterns after fluoropolymer-coated drug-eluting stent implantation. Numbers in parentheses indicate the number of lesions.

Clinical Symptoms by Recurrence Timing

Cases of reocclusion tended to exhibit significantly more severe clinical symptoms than cases of restenosis. In particular, Rutherford category 4 symptoms and acute limb ischemia were more prevalent in cases of reocclusion (Figure 2). A similar trend was observed in the early recurrence group (Figure 3A). In contrast, the clinical symptoms did not differ significantly different between cases of restenosis and reocclusion in the late recurrence group (Figure 3B).

Figure 2.

Clinical symptoms associated with recurrence morphology (i.e., restenosis or reocclusion) after fluoropolymer-coated drug-eluting stent implantation. Numbers in parentheses indicate the number of patients. ALI, acute limb ischemia; R, Rutherford classification.

Figure 3.

Clinical symptoms according to the timing of recurrence after fluoropolymer-coated drug-eluting stent implantation: (A) recurrence within 1 year; (B) recurrence after 1 year. Numbers in parentheses indicate the number of patients. ALI, acute limb ischemia; R, Rutherford classification.

Rate of TLR

Among lesions with recurrence, the overall TLR rate was 72.4%, with no significant difference based on recurrence morphology, namely restenosis or reocclusion (Figure 4). The TLR rate in the early recurrence group was 77.8%, showing no significant difference based on recurrence morphology (75.0% vs. 78.6%; P=0.41; Figure 5A). Meanwhile, the TLR rate in the late recurrence group was 69.4%, without significant differences related to recurrence morphology (74.2% vs. 64.5%; P=0.73; Figure 5B).

Figure 4.

Distribution of target lesion revascularization (TLR) associated with recurrence morphology (i.e., restenosis or reocclusion) after fluoropolymer-coated drug-eluting stent implantation. Numbers in parentheses indicate the number of lesions.

Figure 5.

Distribution of target lesion revascularization (TLR) according to the timing of recurrence after fluoropolymer-coated drug-eluting stent implantation: (A) recurrence within 1 year; (B) recurrence after 1 year. Numbers in parentheses indicate the number of lesions.

Other Outcomes

A summary of the clinical outcomes of this study is present in the Supplementary Table. During the study period, stent fracture and major amputation were observed in 5 (1.1%) and 18 (4.1%) limbs, respectively. All-cause mortality was observed in 116 (29.1%) patients.

Factors Associated With Recurrence

Table 2 presents factors associated with early recurrence after FP-DES implantation. Stent deployment beyond the P1 segment was an independent risk factor for early recurrence. CTO lesions were an independent factor associated with early reocclusion. Female sex, diabetes, not using statins, and long lesions were independently associated with late recurrence (Table 3). Not using statins, warfarin use, and long lesions were independent predictive factors for late reocclusion.

Table 2.

Univariate and Multivariable Regression Analysis for the Association Between Early Recurrence and Reocclusion and Clinical Findings

	Univariate		Multivariable
	HR (95% CI)	P value	HR (95% CI)	P value
Factors for recurrence
Age (per 10-year increase)	0.76 (0.53–1.08)	0.13
Female sex	1.44 (0.73–2.84)	0.30
Diabetes	0.92 (0.48–1.77)	0.79
Hemodialysis	1.80 (0.92–3.52)	0.086
CLTI	1.17 (0.59–2.30)	0.66
Aspirin use	1.06 (0.44–2.55)	0.90
Thienopyridine use	1.10 (0.34–3.60)	0.87
Cilostazol use	0.71 (0.22–2.32)	0.57
DAPT use	1.00 (0.47–2.12)	0.99
Warfarin use	0.95 (0.23–3.96)	0.95
DOAC use	0.81 (0.29–2.28)	0.69
Statin use	0.80 (0.40–1.58)	0.52
CTO	1.76 (0.85–3.65)	0.13
Lesion length ≥150 mm	2.01 (0.84–4.82)	0.12
Severe calcification (PACSS 3/4)	1.06 (0.54–2.06)	0.88
Proximal RVD (per 1-mm increase)	1.12 (0.79–1.58)	0.53
Distal RVD (per 1-mm increase)	0.68 (0.46–1.01)	0.057
Poor below-knee run-off	2.12 (1.10–4.08)	0.025	1.80 (0.92–3.51)	0.085
Popliteal artery lesion	1.90 (0.96–3.76)	0.064
IVUS use	4.18 (0.57–30.47)	0.16
Spot stenting	1.19 (0.29–4.97)	0.81
Stent beyond P1 segment	4.43 (2.08–9.43)	<0.001	3.85 (1.78–8.31)	0.001
Residual stenosis (per 10% increase)	1.03 (0.99–1.07)	0.063
Factors for reocclusion
Age (per 10-year increase)	0.71 (0.48–1.05)	0.083
Female sex	1.40 (0.65–3.04)	0.39
Diabetes	0.98 (0.46–2.06)	0.95
Hemodialysis	1.57 (0.72–3.40)	0.26
CLTI	0.68 (0.29–1.60)	0.38
Aspirin use	0.98 (0.37–2.58)	0.97
Thienopyridine use	1.30 (0.31–5.47)	0.72
Cilostazol use	0.60 (0.14–2.54)	0.49
DAPT use	1.00 (0.43–2.35)	1.00
Warfarin use	1.24 (0.30–5.24)	0.77
DOAC use	0.77 (0.23–2.55)	0.67
Statin use	1.14 (0.50–2.58)	0.76
CTO	3.10 (1.18–8.17)	0.022	3.05 (1.16–8.03)	0.024
Lesion length ≥150 mm	2.41 (0.84–6.93)	0.10
Severe calcification (PACSS 3/4)	1.07 (0.50–2.28)	0.86
Proximal RVD (per 1-mm increase)	1.21 (0.83–1.77)	0.33
Distal RVD (per 1-mm increase)	0.89 (0.55–1.45)	0.65
Poor below-knee run-off	1.89 (0.90–3.96)	0.093
Popliteal artery lesion	1.12 (0.48–2.64)	0.80
IVUS use	2.39 (0.12–4.63)	0.24
Spot stenting	1.57 (0.37–6.60)	0.54
Stent beyond P1 segment	2.84 (1.08–7.48)	0.034
Residual stenosis (per 10% increase)	1.04 (1.00–1.08)	0.045	1.46 (0.99–2.13)	0.051

CI, confidence interval; CTO, chronic total occlusion; HR, hazard ratio. Other abbreviations as in Table 1.

Table 3.

Univariate and Multivariable Regression Analysis for the Association Between Late Recurrence and Reocclusion and Clinical Findings

	Univariate		Multivariable
	HR (95% CI)	P value	HR (95% CI)	P value
Factors for recurrence
Age (per 10-year increase)	0.75 (0.57–0.99)	0.039
Female sex	1.82 (1.07–3.10)	0.028	1.89 (1.10–3.23)	0.021
Diabetes	1.79 (1.03–3.10)	0.038	2.12 (1.22–3.69)	0.008
Hemodialysis	1.31 (0.73–2.34)	0.37
CLTI	1.35 (0.79–2.33)	0.27
Aspirin use	0.88 (0.45–1.74)	0.72
Thienopyridine use	1.47 (0.53–4.05)	0.46
Cilostazol use	0.74 (0.33–1.61)	0.44
DAPT use	1.01 (0.54–1.86)	0.99
Warfarin use	2.26 (0.89–5.72)	0.086
DOAC use	0.78 (0.31–1.94)	0.59
Statin use	0.54 (0.32–0.90)	0.019	0.55 (0.33–0.93)	0.026
CTO	1.66 (0.97–2.86)	0.065
Lesion length ≥150 mm	4.10 (1.86–9.01)	<0.001	4.48 (2.03–9.89)	<0.001
Severe calcification (PACSS 3/4)	1.05 (0.61–1.79)	0.87
Proximal RVD (per 1-mm increase)	0.85 (0.63–1.14)	0.28
Distal RVD (per 1-mm increase)	0.83 (0.60–1.14)	0.24
Poor below-knee run-off	0.79 (0.46–1.37)	0.40
Popliteal artery lesion	1.62 (0.90–2.90)	0.11
IVUS use	1.51 (0.65–3.51)	0.34
Spot stenting	2.12 (0.35–3.57)	0.85
Stent beyond P1 segment	1.79 (0.65–4.96)	0.26
Residual stenosis (per 10% increase)	0.99 (0.96–1.03)	0.76
Factors for reocclusion
Age (per 10-year increase)	0.93 (0.62–1.40)	0.72
Female sex	1.57 (0.72–3.41)	0.26
Diabetes	1.31 (0.63–2.73)	0.48
Hemodialysis	1.20 (0.52–2.79)	0.68
CLTI	2.23 (1.09–4.56)	0.028
Aspirin use	0.90 (0.35–2.35)	0.83
Thienopyridine use	1.45 (0.35–6.06)	0.61
Cilostazol use	0.62 (0.19–2.05)	0.44
DAPT use	1.11 (0.46–2.72)	0.81
Warfarin use	3.76 (1.28–11.00)	0.016	6.21 (2.03–18.98)	0.001
DOAC use	0.30 (0.040–2.16)	0.23
Statin use	0.41 (0.20–0.83)	0.014	0.37 (0.18–0.79)	0.009
CTO	2.10 (0.94–4.70)	0.071
Lesion length ≥150 mm	15.38 (2.10–112.89)	0.007	16.17 (2.20–119.00)	0.006
Severe calcification (PACSS 3/4)	1.05 (0.50–2.24)	0.90
Proximal RVD (per 1-mm increase)	0.88 (0.59–1.32)	0.54
Distal RVD (per 1-mm increase)	0.74 (0.47–1.17)	0.20
Poor below-knee run-off	0.91 (0.43–1.94)	0.81
Popliteal artery lesion	1.78 (0.79–3.99)	0.16
IVUS use	1.48 (0.45–4.89)	0.52
Spot stenting	0.74 (0.10–5.45)	0.77
Stent beyond P1 segment	1.80 (0.43–7.59)	0.42
Residual stenosis (per 10% increase)	1.01 (0.96–1.06)	0.67

Abbreviations as in Tables 1,2.

Discussion

This study focused on the patterns and timing of recurrence following FP-DES treatment in real-world clinical practice and investigated the clinical outcomes and factors associated with recurrence. The early recurrence group exhibited a higher frequency of reocclusion, particularly stent thrombosis, than the late recurrence group. In addition, patients with reocclusion tended to present with more severe symptoms at the time of recurrence than patients with restenosis. The factors influencing recurrence differed according to the timing of recurrence.

Occlusion is a common pattern of recurrence in patients after FP-DES implantation.⁷ However, studies comparing recurrence patterns within the first year, when drug elution persists, and beyond the first year are limited. During the first year, neointimal hyperplasia was suppressed, potentially increasing the risk of thrombotic occlusion. Consistent with this, stent thrombosis was the most common recurrence pattern within the first year in the present study. However, the rate of stent occlusion decreased significantly beyond 1 year after FP-DES implantation. Fluoropolymer-based stents such as Eluvia exhibit prolonged and potent drug-eluting capabilities.¹⁶ This may delay endothelial healing, expose stent struts, and trigger inflammation, potentially increasing the risk of stent thrombosis.

With respect to clinical symptoms at the time of recurrence, the present study found that patients with reocclusion had more severe symptoms than those with restenosis, with a higher prevalence of Rutherford category 4 and acute limb ischemia. A similar trend was observed in the early recurrence group. Meanwhile, the clinical symptoms did not differ between patients with reocclusion and those with restenosis in the late recurrence group. Compared with polymer-free drug-coated stents, FP-DESs better suppress late lumen loss within the first year.¹⁷ However, previous angioscopic studies have indicated that the degree of neointimal hyperplasia increases 1 year after FP-DES implantation,¹⁸ suggesting that FP-DESs may exhibit behaviors similar to those of bare-metal stents (BMS) beyond this period. The mechanism of reocclusion in the case of BMS has been described as continuous neointimal hyperplasia driven by smooth muscle cell proliferation accompanied by intercellular dense collagenous fibers.¹⁹ This suggests that occlusion in the chronic phase after stent implantation may progress gradually over time. Therefore, cases of late occlusion are often not acute occlusions, potentially due to mechanisms such as collateral vessel development. This may explain the less severe symptoms at the time of recurrence in patients with late recurrence.

The rate of subsequent TLR did not differ according to the pattern or timing of recurrence. However, in the early recurrence group, the proportion of patients who did not require TLR because of asymptomatic presentation or symptom improvement was lower among those with reocclusion than among those with restenosis. Conversely, the proportion of patients in which TLR was deemed necessary but not performed was higher in the reocclusion group. These findings align with our results, indicating that early recurrence with reocclusion tends to present with more severe clinical symptoms. In contrast, these trends were not observed in the late recurrence group, with no significant differences in clinical symptoms between patients with reocclusion and those with restenosis.

The factors associated with recurrence after FP-DES implantation have been studied previously;^7,20 however, our investigation focused not only on the timing of recurrence but also on recurrence patterns. Procedural factors significantly influenced EVT outcomes. Limiting the deployment of FP-DES to the P1 segment is critical for ensuring optimal performance,²¹ which aligns with our findings. The popliteal artery is prone to flexion and twisting owing to its anatomical characteristics. These mechanical stresses, along with atherosclerosis progression,²¹ may contribute to early recurrence. Occlusion is a major limitation of balloon-based treatments, including DCBs. Although stent treatment may offer advantages, our study found that CTO lesions were associated with an increased risk of early reocclusion. However, our findings do not suggest that DES should be avoided in cases with CTO. Instead, stent placement is necessary because CTO lesions tend to have a poor prognosis. FP-DESs have already been well established to achieve excellent clinical outcomes,^7,20,22 and remain a feasible and acceptable treatment option for patients requiring stent placement.

Female sex, diabetes, hemodialysis, chronic limb-threatening ischemia, long lesions, and poor run-off have been previously reported to be associated with recurrence after BMS implantation.²³ If we assume that FP-DES may follow a course similar to that of BMS after 1 year, the factors associated with late recurrence identified in the present study are consistent with these findings. The present study found that statin use potentially reduced late recurrence. In addition to improving cholesterol levels by lowering the levels of low-density lipoprotein, statins have been suggested to exert multiple mechanisms of action, commonly referred to as “pleiotropic effects.”²⁴ Statins exert antioxidant, anti-inflammatory, and immunomodulatory effects,^25–27 which may improve endothelial function;²⁸ they also exert antithrombotic effects,²⁹ which may contribute to better long-term outcomes of FP-DES. Statins have been strongly recommended in recent guidelines to reduce mortality and cardiovascular risk in patients with PAD.^6,30 However, statins were used in only approximately 60% of PAD patients in our study. Further, previous studies have also reported a lower statin usage rate in patients with PAD than in those with coronary artery disease or cerebrovascular disease.³¹ This highlights an important clinical issue that needs to be addressed in future practice.

Study Limitations

First, this study had a non-randomized, retrospective design. Second, the study population and number of recurrence events were relatively small, particularly in the early recurrence group. This limited sample size may have reduced the statistical power of the Cox regression analysis, potentially affecting the identification of factors associated with early recurrence. Third, the use of FP-DES was based on the operator’s discretion. Therefore, there is a potential for selection bias. Fourth, our study lacked systemic quantitative angiographic analysis at an independent institute or core laboratory. Fifth, this study included only Japanese patients; therefore, the results should be cautiously extrapolated to other countries. Sixth, this study could not assess the details of the wire passage route and the consequent position of stent implantation (intraluminal or subintimal and its distribution). Finally, the dosage and duration of antiplatelet or anticoagulant therapy, which can affect clinical outcomes after FP-DES treatment, were not estimated in this study. Further studies are required to determine the clinical outcomes of FP-DES in greater detail.

Conclusions

After FP-DES implantation for FPA lesions, the group with early recurrence tended to have a higher incidence of occlusion, especially stent thrombosis, than the group with late recurrence. In the early recurrence group, patients with reocclusion had more severe clinical symptoms than those with restenosis. The method of stent deployment and occluded lesions were associated with early recurrence, whereas sex, diabetes, medications, and lesion length were associated with late recurrence after FP-DES implantation.

Acknowledgments

None.

Sources of Funding

This study did not receive any specific funding.

Disclosures

T.N. is a consultant for Asahi Intecc., BD, Boston Scientific, COOK Medical, Cordis, Kaneka Medix, NIPRO, and OrbusNeich. All other authors report that they have no relationships relevant to the content of this paper.

IRB Information

This study was approved by the Medical Ethics Committee of Ogaki Municipal Hospital (Approval no. 20240425-2) and the ethics committee of each participating hospital.

Data Availability

The deidentified participant data from this study will not be shared.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circj.CJ-25-0054

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