Excimer laser atherectomy combined with drug-coated balloon angioplasty for the treatment of femoropopliteal arteriosclerosis obliterans

Abstract

Introduction

It has been reported that excimer laser atherectomy combined with a drug-coated balloon (ELA+DCB) can achieve better results than simple balloon angioplasty, especially for the treatment of femoropopliteal in-stent restenosis. However, reports on the application of ELA+DCB in China for femoropopliteal arteriosclerosis obliterans are lacking. This study focuses on analysing the effectiveness and safety of ELA+DCB.

Methods

This was a single-centre retrospective study that enrolled patients from November 2016 to January 2019 who had femoropopliteal arteriosclerosis obliterans treated by ELA+DCB. Preoperative demographics, operative details and postoperative follow-up outcomes were analysed statistically.

Results

There were 43 patients with an average patient age of 68.0±8.6 years; 79.1% were male. In 30 cases, the lesions were de novo and the others were in-stent restenosis (ISR). During the procedure, flow-limiting dissection (48.8%) was the main adverse event and there were 17 bailout stent implantations due to dissection. Mean (±sd) ankle–brachial index (ABI) in the patients was 0.42±0.31 before the operation and 0.83±0.13 before discharge. The mean (±sd) follow-up time was 29.35±9.71 months. The primary patency rate was 66.8%, 64.3% and 60.9% at 12, 24 and 36 months. Freedom from target lesion revascularisation (TLR) was 85.7%, 80.7% and 75.3% at 12, 24 and 36 months. Rutherford categories also greatly improved during follow-up. Overall mortality was 6.9% (3/48), and no deaths were related to the intervention.

Conclusion

The use of ELA+DCB had good clinical benefit for femoropopliteal arteriosclerosis obliterans, which had good primary patency and freedom from TLR, although intraoperative complications still required attention. Multicentre randomised controlled trials with long-term follow-up are needed.

Introduction

With the rapid development of endovascular therapy in recent decades, simple balloon angioplasty and stent implanting have become conventional treatments for patients with peripheral vascular disease. One of the most commonly treated lower limb vessels is femoropopliteal artery; although patency in this area is challenging,¹ this relates to many factors. The mechanical forces on this area are complex, including compression, flexion and torsion, and length of the lesions is longer.

Based on these challenges, a concept of ‘leave nothing behind’ has been put forward. Atherectomy has been chosen to treat peripheral artery disease which leaves no permanent implants in the vessels. Endovascular atherectomy devices are divided into four types based on the mechanism used to remove the atheroma: excimer laser, rotational, directional and orbital. Our study focused on excimer laser atherectomy (ELA). The wavelength of the excimer laser is 308nm, and it can deliver short bursts (125ns) of energy leading to ‘photoablation’ of the plaque, avoiding damage to the surrounding tissue. This ablation is photochemical rather than photothermal, and produces subcellular debris.² Application of the ELA has shown good outcomes in patients with either critical limb ischaemia or femoropopliteal in-stent restenosis (ISR).^3,4

The application of a drug-coated balloon (DCB) in lower extremity arterial disease has developed rapidly in recent years. Anti-hyperplasia drugs are carried on the surface of the balloon, inhibiting intimal hyperplasia and thereby inhibiting restenosis.⁵ Endovascular atherectomy combined with a DCB to treat lower extremity arteriosclerosis obliterans has become a hot topic of current research. It has been reported that an ELA+DCB combination can achieve better results than simple balloon angioplasty, especially in the treatment of femoropopliteal ISR.⁶

However, reports about the application of ELA+DCB in China for femoropopliteal arteriosclerosis obliterans are lacking, and so this study focuses on analysing the effectiveness and safety of ELA+DCB.

Methods

Study design

Patients in our hospital with femoropopliteal arteriosclerosis obliterans who received ELA+DCB between November 2016 and January 2019 were enrolled retrospectively. Follow-up was at 6, 12, 18 and 24 months, and annually thereafter. The inclusion criteria for the study were: (1) all patients gave informed consent; (2) patients had lifestyle-limiting disease, pain on rest, ulceration or gangrene; (3) femoropopliteal artery stenosis ≥70%, or occlusion based on vascular ultrasound or digital subtraction angiography; and (4) patient compliance was good and regular follow-up was possible. Exclusion criteria were: (1) life expectancy of <1 year; (2) allergy to contrast agents, heparin or acetylsalicylic acid; (3) serious cardiovascular and cerebrovascular disease; (4) immunosuppressive therapy; and (5) coagulation disorders.

Treatment and medical therapy

Device and material

The ELA device used was a Turbo-Elite laser catheter (Philips Medical Systems, Inc.), the DCB was an orchid paclitaxel-coated balloon (Acotec Scientific) and the stent was a Bard, Biotronik, or Medtronic Bare Nitinol self-expanding stent.

Preoperative preparation

Computed tomography angiography was performed to determine the femoropopliteal artery lesions; liver, kidney and coagulation function were tested; and an iodine allergy test was performed. Before surgery, patients were given aspirin (100mg/d) and clopidogrel (75mg/d) orally for three days.

Endovascular interventions

After local anaesthesia, access was established by anterograde puncture in the ipsilateral femoral artery or retrograde puncture in the contralateral femoral artery after intravenous heparin administration (50–70U/kg) and diagnostic angiography.

All patients first underwent ELA, then after removing the plaques, DCB was applied in all cases. Different DCB specifications were selected according to the lengths of the affected vessels. Usually, the dilation and attachment time of the DCB was 180s, and the length of the balloon exceeded the proximal and distal ends of the target lesion by 1cm to avoid omission of the target lesion. If flow-limiting dissections or residual stenosis >50% occurred, the simple balloon was dilated for >2min. If there was still stenosis, serious limiting or perforation, bailout stents could be used.

Postoperative medical advice

After surgery, patients were prescribed clopidogrel (75mg/d) and aspirin (100mg/d) orally for 12 months. Patients were encouraged to exercise, quit smoking and actively control their blood sugar, blood pressure and blood lipids. For patients with lower extremity ulcers and gangrene, dressings were changed regularly in the outpatient clinic.

Follow-up

At 3, 6 and 12 months, and annually thereafter, patients received follow-up. The main evaluation indexes in each follow-up included clinical manifestations (relief of pain on rest, ulcer healing, claudication distance), physical examination, Rutherford classification and vascular ultrasound examination.

Endpoints and definitions

The primary patency rate was the main efficacy endpoint in this study. If the patient had no significant restenosis (<50%) on vascular ultrasound and no clinically driven reintervention, we defined the patient as having primary patency. Secondary endpoints included freedom from clinically driven target lesion revascularisation (CD-TLR) and technical success. If the patient was free from revascularisation with clinical symptoms (intermittent claudication, pain on rest or worse), we defined the patient as freed from CD-TLR. If after surgery, treatment of the lesion was successful with final residual stenosis of <30%, we defined that a technical success. Primary safety endpoints included all-cause death, unplanned major amputation and adverse events (flow-limiting dissection, major bleeding, perforation, urgent target lesion thrombolysis).

Statistical analysis

Categorical variables are shown as n (%). Continuous variables were compared by Student’s t-test and are shown as means±sd. Freedom from CD-TLR and primary patency rates were estimated using the Kaplan–Meier method. Statistical significance was set at p<0.05. SPSS (version 20.0) was the main software used for the analyses.

Results

From November 2016 to January 2019, 43 patients were treated. The mean age of the patients was 68.0±8.6 years, and 79.1% were male. The patients had various comorbidities, including hypertension (62.8%), diabetes mellitus (55.8%), smoking history (48.8%), intervention history (44.2%), cerebrovascular disease (25.6%) and coronary artery disease (14%). Thirty cases were de novo lesions and 13 were ISR. Mean lesion length was 182.56±83.21mm. The most common lesions were TASC II types B (32.6%) and D (46.5%); 7% of cases were TASC II type A and 14% of cases were TASC II type C (Table 1). Most patients had severe symptoms. Rutherford category 2 accounted for 2.3% of cases, category 3 for 67.4%, category 4 for 14.0%, category 5 for 14% and category 6 for 2.3% of cases (Table 4).

Table 1 .

Demographic and clinical characteristics of the patients

Characteristic	N = 43
Age (years)	68.0±8.6
Male	34 (79.1)
Hypertension	27 (62.8)
Diabetes mellitus	24 (55.8)
Coronary artery disease	6 (14)
Cerebrovascular disease	11 (25.6)
Smoking history	21 (48.8)
Intervention history	19 (44.2)
De novo	30 (69.8)
Lesion length (mm)	182.56±83.21
TASC II classification
A	3 (7)
B	14 (32.6)
C	6 (14)
D	20 (46.5)

Values are given as n (%) or mean±sd.

Table 4 .

Change in Rutherford category

Rutherford category	Preintervention	Postintervention
1	0	33
2	1	8
3	29	2
4	6	0
5	6	0
6	1	0
			p<0.0001

During the procedure, flow-limiting dissection (48.8%) was the main adverse event, and there were 17 bailout stent implantations due to this dissection. Other adverse events were embolism (7%) and vessel perforation (4.7%); there were no deaths (Table 2). Mean ABI was 0.42±0.31 before the operation and 0.83±0.13 before discharge (p=0.002) (Table 3). The technical success rate was estimated at 100%.

Table 2 .

Perioperative complications in patients

Complication	n (%)
Flow-limiting dissection	21 (48.8)
Embolism	3 (7)
Vessel perforation	2 (4.7)
Death	0

Table 3 .

Change in ABI

	Preintervention	Postintervention	p-value
ABI	0.42 ± 0.31	0.83 ± 0.13	0.002

ABI = Ankle–brachial index

Mean follow-up time was 29.35±9.71months. The primary patency rate was 66.8%, 64.3% and 60.9% at 12, 24 and 36 months (Figure 1a). The freedom from TLR rate was 85.7%, 80.7% and 75.3% at 12, 24 and 36 months (Figure 1b). Rutherford category also greatly improved postoperatively (Table 4, Figure 2). Overall mortality was 6.9% (3/48); one patient died at 3 months after the operation due to cardiac failure, two patients died at 12 months after the operation due to cerebral infarction. One patient required a toe amputation at 1 month.

Figure 1 .

Kaplan–Meier curves showing (a) total primary patency rate and (b) freedom from target lesion revascularisation (TLR)

Figure 2 .

Changes in Rutherford categories

Discussion

Optic fibres were used to conduct an excimer laser, of wavelength 308nm, located in the blue spectrum, which is a cold laser. Each photon carries enough energy to break a single carbon–carbon bond. Intracellular lipids and proteins absorb this high energy and are quickly destroyed. The light penetration depth is around 0.05mm which avoids damaging surrounding tissues. Finally, the intracellular liquid is vaporised. This method can have theoretical benefit in terms of clinical emboli because the microscopic subcellular debris created are washed away distally.⁷ The LACI (laser angioplasty in critical limb ischemia) trial in Belgium was an earlier study of critical limb ischaemia treated by ELA. At 6 months after the operation, the limb salvage rate was 38/42 (90.5%), which confirmed that ELA had excellent limb salvage rates.³ The EXCITE ISR Trial (EXCImer Laser Randomised Controlled Study for Treatment of Femoropopliteal In-Stent Restenosis) was the first randomised, prospective, large study to demonstrate the superiority of ELA combined with percutaneous transluminal angioplasty (ELA+PTA) compared with PTA alone for treating femoropopliteal ISR. After 6 months, the freedom from TLR rate of ELA+PTA compared with PTA was 73.5% vs 51.8% (p<0.005); the major adverse event rates at 30 days were 5.8% vs 20.5% (p<0.001), respectively.⁴ Application of the ELA has shown good outcomes for patients with either critical limb ischemia or femoropopliteal ISR.

Compared with PTA alone, DCBs have shown excellent outcomes in preventing restenosis in de novo and ISR lesions of the femoropopliteal artery.^8,9 Although the same procedural complications as PTA, residual stenosis, bailout stenting and dissection, often occur in DCB application alone, endovascular atherectomy can solve these problems to some extent. Therefore, ELA+DCB to treat lower extremity arteriosclerosis obliterans has become a hot topic of current research. Damianos et al¹⁰ showed that the combination of ELA+DCB vs ELA+balloon angioplasty (BA) improved 2-year TLR rates and decreased rates of bail-out stenting in treatment of femoropopliteal ISR; bail-out stenting rates were lower in the ELA+DCB group (32% vs 57%, p=0.008). The 12-month KM estimates for freedom from TLR or restenosis were 66% in the LA+DCB group vs 46% in the LA+BA group. The 24-month KM estimates were 45% in the LA+DCB group vs 24% in the LA+BA group.

ELA+DCB also has high procedural success rates, long-term patency and appears to be practicable and safe for chronic obstructive femoropopliteal arterial disease. Liu et al found a technical success rate of 100% and procedural success rate of 88.2%. Bailout stenting was required in 5 of the 17 patients (29.4%) and the 12-month primary patency rate was 82.4%. The clinically driven TLR rate was 5.9% at 12 months.¹¹ In our study, the primary patency rate was 66.8%, 64.3% and 60.9% at 12, 24 and 36 months. The rate of freedom from TLR was 85.7%, 80.7% and 75.3% at 12, 24 and 36 months, and the results showed the excellent effectiveness of ELA+DCB for treating femoropopliteal arteriosclerosis obliterans. The ISR subgroup had a similar primary patency rate and freedom from TLR.

The main adverse events during the procedure should be noted. There were 21 cases (48.8%) of flow-limiting dissection, and 17 bailout stent implantations due to the dissection. On the one hand, such a high incidence was related to the complexity of the lesion (46.5% cases were TASC II D); particularly for severe calcification, localised calcium deposits have a direct role in promoting dissection.¹² On the other hand, contrast media can increase energy absorption and lead to dissection or perforation, so the laser should not be used in the presence of contrast media. Blood can also absorb laser energy during the operation, and blood and contrast media should be removed by saline flushing during laser atherectomy;¹³ vessel perforation (2/43, 4.7%) was also related to inadequate saline flushing. To reduce the embolism incidence rate (3/43, 7%), the device should be advanced slowly at a rate of 0.5–1mm/s;¹⁴ in addition, the catheter should be pushed at a constant speed. In case of a severe calcification plaque, the frequency can be increased and the energy reduced as appropriate. The light tube was paused in the plaque for ablation until the tube was ready to pass calcified lesions. For long segments and severe calcification, if there was only one distal outflow tract, a distal protective device should be considered to prevent distal embolism.

After treatment with drug-eluting devices, Katsanos et al¹⁵ showed increased mortality, although other studies conclude that there is no evidence that drug-coated devices increase all-cause mortality compared with non-drug-coated devices in treating femoropopliteal artery diseases;¹⁶ this is controversial. In our trial, overall mortality was 6.9% (3/48), none of the deaths were related to the intervention and further research is needed.

Atherectomy has not been recommend as the primary method to treat peripheral arterial disease.¹⁷ Although for complex lesions (chronic total occlusions, longer lesions, heavy calcium), atherectomy can have better results than standard endovascular treatment, ELA can maximise acute luminal gain, remove the calcium barrier and can facilitate diffusion of the drug on the DCB. This combination will give excellent results.

Limitations

Our study has some limitations. First, this was a real-world study and thus our results should be interpreted in the context of observational research and its limitations. Second, the sample is relatively small, based on the medical insurance policy in China. The cost of the procedure limits use the ELA+DCB. Third, ours is a single-arm study, and further contrast trials are needed. Therefore, large sample, multicentre, randomised controlled studies are needed.

Conclusion

The use of ELA+DCB gave good clinical benefit for femoropopliteal arteriosclerosis obliterans, which showed good primary patency and freedom from TLR, although intraoperative complications still need our attention. Multicentre randomised controlled trials with long-term follow-up are needed.