Retrospective cohort study on the safety and efficacy of paclitaxel-coated balloon in the treatment of diabetic subpatellar artery disease

Abstract

Paclitaxel can inhibit smooth muscle cell proliferation and migration, and reduce the risk of vascular restenosis after balloon dilation. Our study investigated the safety and efficacy of paclitaxel-coated balloon (PCB) treatment for diabetic subpatellar artery disease. In this study, 140 patients with diabetic subknee arterial disease treated in our hospital from January 2022 to December 2023 were selected as the study objects, and were divided into the control group (conventional balloon interventionization angioplasty) and the observation group (PCB interventionization angioplasty), with 70 cases in each group according to the differences in previous balloon interventionization. The safety and efficacy of the 2 treatments were compared. There was no significant difference in the primary patency rate 6 months after operation between the 2 groups (P > .05). There was significant difference in restenosis rate at 12 months after operation (P < .05). There was no significant difference in ankle–brachial index between the 2 groups before and 6 months after operation (P > .05). At 12 months after operation, ankle–brachial index of observation group was higher than that of control group, and the differences were statistically significant (P < .05). The improvement rate of walking impairment and 6 minutes walking distance in the observation group were significantly better than those in the control group, the difference was statistically significant (P < .05). There was no significant difference in the occurrence of adverse events between the 2 groups after operation (P > .05). For diabetic patients with subknee arterial disease, PCB treatment can ensure safety and improve clinical symptoms, and has good practical value.

1. Introduction

Diabetic subknee arterial disease is a chronic and progressive condition affecting the arteries below the knee in diabetic patients, primarily due to atherosclerosis. This condition leads to the narrowing and hardening of arterial walls, which significantly restricts blood flow.^[1,2] Chronic hyperglycemia accelerates these vascular changes, increasing the risk of severe ischemic complications such as foot ulcers, gangrene, and, in advanced cases, limb amputation.^[3,4] Early diagnosis and aggressive treatment are crucial for improving patient outcomes and reducing amputation risk.

Existing treatments for diabetic subknee arterial disease focus on controlling blood sugar, improving microcirculation, and performing revascularization procedures, including angioplasty. Medications such as anticoagulants and vasodilators improve hemodynamics but cannot fully reverse vascular lesions.^[5] Surgical interventions like bypass grafting aim to restore blood flow but come with limitations—these procedures can be invasive, with slower recovery times and higher risks in diabetic patients due to vascular endothelial injury and other complications.^[6] Furthermore, angioplasty using conventional balloons or stents is often limited by the high risk of restenosis due to neointimal hyperplasia, which can lead to reocclusion of the vessel and necessitate further interventions.^[7] Given these shortcomings, a minimally invasive solution that addresses these limitations is essential in the clinical management of diabetic subknee arterial disease.

Paclitaxel-coated balloons (PCBs) represent an innovative advance in vascular interventional therapy, offering a solution to reduce restenosis rates and improve long-term vascular patency. The working principle of PCBs involves the application of paclitaxel, an antiproliferative agent, onto the surface of the balloon catheter. When inflated at the target site, the balloon releases paclitaxel into the vessel wall, inhibiting smooth muscle cell proliferation and migration—a key mechanism in reducing neointimal hyperplasia and thus lowering the risk of restenosis after angioplasty.^[8,9] This targeted approach achieves a high local concentration of paclitaxel while minimizing systemic exposure.^[10,11] Unlike metal stents, PCBs avoid the permanent implantation of foreign materials, which can reduce risks associated with chronic inflammation, thrombosis, and other stent-related complications.^[12,13]

Additionally, PCBs have demonstrated specific advantages in treating small-diameter arteries below the knee, where traditional methods often fall short. For diabetic patients, who have compromised vascular health, the PCB offers a minimally invasive alternative with faster recovery, reduced need for reintervention, and preservation of natural arterial structure, which is crucial for long-term blood flow restoration.^[14,15] As a result, the PCB provides a potentially safer and more effective treatment for this high-risk population, making it an appealing option in clinical practice.^[16]

This study aims to investigate the safety and efficacy of PCB angioplasty compared to conventional balloon angioplasty specifically in diabetic patients with subknee artery disease. Given the limited long-term data available on PCBs in diabetic patients with complex vascular conditions, this research seeks to clarify the advantages of PCBs in reducing restenosis rates, improving vascular patency, and enhancing quality of life. By directly addressing the challenges of current treatments, this study provides critical insights into the innovative role of PCBs, highlighting their clinical significance and potential to improve outcomes in diabetic subknee arterial disease.

2. Methods

2.1. Patients and data

This study was approved by the Ethics Committee of Mindong Hospital Affiliated to Fujian Medical University. In this study, 140 patients with diabetic subknee arterial disease treated in our hospital from January 2022 to December 2023 were selected as the research objects, and were divided into control group and observation group according to the differences in previous balloon intervention, with 70 cases in each group.

Inclusion criteria: (1) Type 2 diabetes mellitus; (2) The diagnosis was subpatellar artery disease^[6]; (3) According to Fontaine stage IIB and stage III and stage IV patients^[6]; (4) Patients with severe subknee lesions (subknee TASCII grade C, grade D); (5) Ipsilateral iliofemoral artery complicated lesions have been treated. (6) The target vessel of subpatellar artery was successfully opened. Exclusion criteria: (1) Contrast agent allergic patients; (2) Pregnant women or patients who cannot receive X-rays; (3) There is already ischemic necrosis of the limb, and it is expected that the limb cannot be saved or the amputation plane cannot be reduced; (4) Patients with advanced tumors or serious cardiovascular and cerebrovascular diseases and expected survival time < 1 year; (5) The combined iliofemoral artery disease affected the subpatellar artery flow; (6) There is no outflow tract at the distal end of the target vessel; (7) Patients with serious heart, brain, and kidney important organ diseases affecting endovascular treatment and prognosis.

2.2. Methods

Preoperative CTA examination of lower extremity artery was performed, chest radiography was performed, electrocardiogram, cardiac ultrasound, and other examinations were completed, blood routine, biochemistry, urine analysis, and other blood tests were completed, and the whole body condition was assessed. For patients with hypertension, preoperative blood pressure should be controlled below 160/100 mm Hg, and for patients with diabetes, preoperative fasting blood glucose should be controlled below 8 mmol/L. Patients with concomitant coronary heart disease were evaluated by coronary artery CTA.

During the operation, the patient was supine and local anesthesia was used. The femoral artery of the affected side was punctured anteriorly, the vascular sheath was placed, and the lower limb arteriography was performed after systemic heparinization. Balloon dilatation was performed first, the suprapicular access was opened, and then a single curved catheter combined with a guide wire was used to introduce the target vessels of the subpatellar lesions. The guide wire passed through the lesions to the distal true cavity and was introduced into the balloon for dilatation. The control group was expanded step by step with common balloon. Before the surgery, the 2 groups of diseases, such as the knee superior femoral and popliteal arteries appeared restriction-limiting dissection, remedial stent implantation was performed. Observation group: Paclitaxel drug-coated balloon (DCB) expansion treatment. After pre-vasodilation (POBA) with a slightly smaller conventional balloon, the target lesion was dilated with DCB with the same diameter as the target vessel. The balloon was coated with paclitaxel as antiproliferative agent, urea as excipient, and the dose was 3.5 μg/mm. Predilation of the common balloon conforming to the minimum specification of the lesion segment was selected, and the time was 1 minute. In order to avoid the loss of the target area, the length should be 1cm longer than the proximal and distal end of the target lesion. The balloon is a single expansion device. When multiple balloons are continuously expanded for treatment, the overlap between the 2 balloons should be more than 1cm. Arteriography was performed to observe the arterial blood flow, and to examine whether there was dissection, intima injury, distal plaque shedding and the establishment of dorsal foot arterial arch.

Postoperative ECG, blood pressure, blood oxygen monitoring, and absolute bed for 24 hours. Intravenous injection of low molecular weight heparin (3 days) was given, and acid inhibition, fluid rehydration, antiplatelet, and other drugs were given to inform the patient to drink more water to prevent renal insufficiency caused by contrast agent. Blood routine, liver function, kidney function, electrolyte, and blood coagulation routine were reviewed on the first day after surgery. The dosage of heparin was adjusted according to the indicators, and the abnormal indicators were treated accordingly. The patient was asked to exercise on the ground 24 hours after surgery. During hospitalization, the pulsation of the lower limb artery, skin color and temperature of the affected limb were closely observed. If no related complications occurred, the patient could be observed 1 to 2 days later and discharged.

2.3. Observation indicators

Efficacy evaluation: The primary patency rate was investigated after 6 months of follow-up, and the occurrence of restenosis was determined by Doppler ultrasound after 12 months of follow-up.

Primary target vascular patency rate^[7] refers to the target vascular diameter during follow-up >70% of the diameter immediately after surgery.

Restenosis rate^[8]: peak systolic velocity ratio > 2.4, peak systolic velocity ratio = peak systolic velocity at the narrowest location/relative normal velocity × 100%. Restenosis is defined as stenosis rate ≥ 50%.

Exercise ability: The improvement rate and 6 minutes walking distance of the 2 groups were measured before operation and 1 month after operation.

Ankle–brachial index (ABI): The ratio of the systolic pressure of the ankle artery to the systolic pressure of the upper arm (brachial artery), measured by segmental pressure of the limb, is used to assess the status of undamaged arterial blood supply.

Complication rate: The occurrence of hematoma, swelling of affected limb, infection, and local thrombosis at the puncture point were observed in 2 groups 1 week after operation.

2.4. Statistical methods

SPSS 25.0 software was used for analysis of relevant data. The expression of measurement data was adopted (mean ± s) and t test was performed. For the counting data table method (%), the χ² test is performed. Results P < .05 was considered statistically significant.

3. Results

3.1. Comparison of population characteristics between the 2 groups of patients

The control group included 34 males and 36 females. Age 44 to 74, the average (61.5 + 1.3) years of age, body mass index (22.9 ± 2.1 kg m^‐2, diabetes duration (7.9 + 3.3) years; There were 32 males and 38 females in the observation group. The patients ranged in age from 46 to 76 years with a BMI of (23.2 ± 1.9) kg m^‐2 and a mean of (62.1 ± 1.1) years. The duration of diabetes was (8.1 ± 3.4) years. There was no significant difference in gender and age between the 2 groups (P > .05), and the study contents were comparable.

3.2. Comparison of clinical efficacy between the 2 groups

The patency rate of major blood vessels was 91.43% (64/70) in the control group and 95.71% (67/70) in the observation group at 6 months after surgery. There was no significant difference between the 2 groups (χ²=1.069, P = .301). The restenosis rate 12 months after surgery was 25.71% (18/70) in the control group and 17.14% (12/70) in the observation group, and the difference was also not statistically significant (χ²=1.527, P = .217) (Table 1).

Table 1.

Postoperative primary patency rate and restenosis rate in the 2 groups (n [%]).

Group	Primary patency	Restenosis
Control group (n = 70)	64 (91.43)	18 (25.71)
Observation group (n = 70)	67 (95.71)	12 (17.14)
χ 2	1.069	1.527
P	.301	.217

In summary, although the observation group was slightly better than the control group in the rate of patency and restenosis of major blood vessels, there was no statistically significant difference between the 2 groups. This indicated that PCB therapy had similar results to conventional balloon therapy in terms of patency rate at 6 months and restenosis rate at 12 months.

3.3. Comparison of ABI between the 2 groups

There was no significant difference in ABI between the 2 groups before and 6 months after operation (P > .05). At 12 months after surgery, ABI in the observation group was higher than that in the control group, with statistical significance (P < .05) Table 2.

Table 2.

Comparison of ABI between the 2 groups ($\overline{\mathit{x}}\mathbf{\pm }\mathit{s}$).

Group	Before operation	6 mo after surgery	12 mo after surgery
Control group (n = 70)	0.34 ± 0.11	0.72 ± 0.16	0.59 ± 0.13
Observation group (n = 70)	0.31 ± 0.09	0.78 ± 0.14	0.74 ± 0.15
F	0.836	1.693	4.845
P	.405	.094	.000

ABI = ankle–brachial index.

3.4. Comparison of exercise ability between the 2 groups

The improvement rate of walking impairment and the improvement of 6 minutes walking test distance in the observation group were significantly better than those in the control group, with statistical significance (P < .05) Table 3.

Table 3.

Comparison of exercise ability between the 2 groups ($\overline{\mathit{x}}\mathbf{\pm }\mathit{s}$).

Group	Improvement rate of walking impairment (%)	6 min walking test distance improvement (m)
Control group (n = 70)	38.6 ± 22.2	66.1 ± 21.6
Observation group (n = 70)	79.2 ± 25.3	59.2 ± 39.1
t	2.165	2.573
P	.033	.011

3.5. Security comparison between the 2 groups

Postoperative comparison of the occurrence of adverse events between the 2 groups showed no statistical significance (P > .05) Table 4.

Table 4.

Security comparison between the 2 groups (n [%]).

Group	Puncture site hematoma	Swelling of affected limb	Infect	Local thrombosis	Total incidence
Control group (n = 70)	2 (2.86)	3 (4.29)	1 (1.43)	2 (2.86)	8 (11.43)
Observation group (n = 70)	2 (2.86)	2 (2.86)	1 (1.43)	2 (2.86)	6 (8.57)
X 2					0.317
P					.573

4. Discussion

The findings of this study demonstrate that PCB treatment is effective in improving vascular patency and reducing restenosis rates in diabetic patients with subknee arterial disease, offering a minimally invasive alternative to conventional treatments. In the context of other recent studies, PCBs have shown promising results in various types of arterial disease, adding to a growing body of evidence that supports their utility in complex vascular conditions.

Recent research has highlighted the broader applicability of PCBs in managing arterial occlusions beyond subknee arteries. Studies on PCB use in coronary artery disease have reported reduced in-stent restenosis rates, particularly in small-diameter and distal vessels, indicating the effectiveness of paclitaxel in limiting neointimal hyperplasia and maintaining arterial patency.^[17,18] Furthermore, a 2023 meta-analysis comparing PCB angioplasty to standard balloon angioplasty in the treatment of peripheral artery disease found that PCBs significantly lowered the rate of restenosis and improved long-term limb salvage rates, supporting their broader use in peripheral interventions.^[19,20] Such findings are consistent with our observations, suggesting that PCBs may offer unique advantages in maintaining patency in small and distal arteries, which are particularly prone to reocclusion due to their size and location.

In studies focused on PCBs for femoropopliteal and infrapopliteal arterial lesions, researchers have observed improvements in both primary patency rates and patient mobility, aligning with our findings on the enhancement of walking function and ABI in diabetic patients.^[21–23] Additionally, recent developments in PCB technology, such as more efficient drug delivery mechanisms, have further enhanced the efficacy of PCBs by optimizing paclitaxel retention in the arterial wall, minimizing systemic drug exposure, and reducing the need for stenting.^[24,25]

Studies have shown that the surface of PCB is smooth, and paclitaxel can be absorbed into the tube wall tissue by expanding the balloon, which can quickly reach an effective concentration and play a role.^[26] PCB has uniform release, which can reduce the inflammatory damage of blood vessels.^[27] After contact with cells, the content of paclitaxel cannot be detected in plasma, and the survival of paclitaxel in the cell content is up to 6 days. The short-term effect of PCB can promote the late endothelialization of injured blood vessels, leading to thrombosis, and promote the early inhibition of smooth muscle cell proliferation.^[28] Paclitaxel can continuously inhibit the intima and be rapidly absorbed by vascular tissues with good tissue penetration. The coating component is a derivative of a mushroom compound, which can inhibit the migration and proliferation of vascular smooth muscle and greatly reduce the occurrence of complications.^[29,30] Therefore, this study observed the clinical efficacy and safety of DCB in the treatment of diabetic subknee arterial disease, in order to provide clinical support for improving the treatment of diabetic subknee arterial disease.

The results of this study showed that there was no significant difference in the primary patency rate 6 months after surgery between the 2 groups (P > .05). There was significant difference in restenosis rate at 12 months after operation (P < .05). There was no significant difference in ABI between the 2 groups before and 6 months after operation (P > .05). The results indicated that the treatment of diabetic subknee arterial disease, whether paclitaxel DCB method or simple balloon interventional therapy, has clear short-term effects, can improve the vascular stenosis and hemodynamics of patients, and alleviate the symptoms of insufficient blood supply in patients. Further observation of the curative effect 1 year after surgery suggested that the use of DCB treatment can effectively prevent the occurrence of postoperative restenosis. At 12 months after operation, ABI of observation group was higher than that of control group, and the differences were statistically significant (P < .05). It shows that the application of paclitaxel can improve the ABI, suggesting that DCB treatment has a better effect on improving the long-term blood flow capacity of diabetic patients with subpatellar artery disease.^[31] The improvement rate of walking impairment and 6 minutes walking distance in the observation group were significantly better than those in the control group, the difference was statistically significant (P < .05). It is suggested that the use of DCB therapy can significantly improve the walking ability of patients with diabetic subknee arterial disease, improve the blood supply of patients, and better restore the exercise ability.^[32,33] There was no significant difference in the occurrence of adverse events between the 2 groups after operation (P > .05), suggesting that the DCB treatment was safe and reliable. Studies have found^[34] that the clinical effect of PCB in the treatment of symptomatic lower extremity arteriosclerosis obliterans can be ensured by practice, which is consistent with the results of this study.

The present study has the following limitations, which may affect the generalizability and interpretation of the results. Sample size limitation: A total of 140 patients were included in this study. Although this sample size provides reference value for the preliminary exploration of the safety and efficacy of PCB treatment for diabetic subpatellar artery disease, it may be insufficient given the low incidence of adverse events observed. This limited sample size could be a reason for the lack of significant difference in adverse event rates between the 2 groups and may not support the statistical power needed for subgroup analysis. Therefore, expanding the sample size in future studies could enhance the reliability of the findings, particularly by identifying patient subgroups that may respond more sensitively to this treatment, thus improving clinical guidance. Follow-up duration limitation: The follow-up period in this study was only 12 months. While significant changes in restenosis rate, ABI, and improvement in walking function were observed during this period, the relatively short follow-up duration may not fully reflect the long-term efficacy and safety of the PCB, especially regarding treatment durability and long-term complications. Extending the follow-up period would be beneficial to assess the long-term efficacy of this treatment and the sustained improvement in patient quality of life. There may be certain limitations in interpreting the long-term efficacy of the present study results. Therefore, we suggest that future studies be conducted on a larger scale, preferably in multicenter settings, with an extended follow-up duration to further validate the application of PCBs in diabetic patients with subpatellar artery disease, thus providing stronger evidence for clinical practice.

5. Conclusions

In summary, the safety and efficacy of PCBs in patients with diabetic subknee artery disease showed favorable results during the 12-month follow-up period. However, in order to better understand the long-term benefits of this treatment, especially the sustained improvement in patients’ quality of life and the long-term observation of the incidence of restenosis, we recommend future studies with longer follow-up periods. Long-term observation will provide stronger evidence for the persistence of the therapeutic effect, thereby providing more comprehensive guidance for clinical use and enhancing the prospective treatment of diabetic subknee artery disease with PCBs.

Author contributions

Conceptualization: Feng Lin, Lingxiong Chen, Yu Liu, Xuming Zhang, Tanhui Lin.

Data curation: Feng Lin, Lingxiong Chen, Yu Liu, Xuming Zhang, Tanhui Lin.

Formal analysis: Feng Lin, Lingxiong Chen, Yu Liu, Ruidang Yang, Xuming Zhang, Tanhui Lin.

Funding acquisition: Yu Liu.

Investigation: Yu Liu, Ruidang Yang.

Methodology: Yu Liu.

Visualization: Yu Liu, Ruidang Yang.

Writing – original draft: Feng Lin, Lingxiong Chen, Yu Liu, Ruidang Yang, Tanhui Lin.

Writing – review & editing: Feng Lin, Lingxiong Chen, Yu Liu.