Vessel preparation can potentially contribute to better peri- and post-procedural outcomes in complex lesions, especially in the case of severe vessel wall calcifications. Vessel preparation is a broad term and includes mechanical atherectomy MA: directional atherectomy (DA), rotational atherectomy (RA), orbital atherectomy (OA), laser atherectomy (LA), scoring balloons and intravascular lithotripsy (IVL). MA devices remove atheroma by abrasion, shearing, drilling and aspiration, while LA devices remove plaque and thrombus by vapourisation and modify vessel wall calcifications, creating better compliance. Scoring balloons feature wires mounted on the surface of the balloons, which act as microsurgical blades to generate controlled plaque incision. IVL uses an angioplasty balloon, which generates pulsating sound waves that cause microfractures in the calcification of the intimal and medial layer of the vessel wall.

These are relatively expensive medical devices and/or they are of additional value is still uncertain. Studies have shown that there are important predictors of a good technical and durable outcome of a PTA. Lesion length, degree of vessel wall calcification and chronic total occlusion (CTO) are the most important of these. Severe vessel wall calcification limits the stretchability of the artery, leading to more dissections and more frequent stent placement. The goal of vessel preparation is to reduce the number of dissections and improve vessel wall elasticity. In CTOs, it also aims to ‘debulk’, which means less plaque and thrombus material remains in the vessel and a PTA will have a better outcome. Whether the use of vessel prep in the femoro-popliteal pathway is indicated will be explored in this module.

Freedom from binary restenosis/primary patency (critical)

One year

Two years

Reintervention based on symptomatic restenosis (critical)

Quality of life (important)

Amputation (important)

Complications (important)

Dissections

Perforations

Mortality (important)

Description of studies

Böhme (2021) performed a prospective, randomized controlled trial to evaluate the safety and effectiveness of preparing in-stent femoropopliteal lesion with photo ablative laser atherectomy or plain balloon angioplasty prior to drug-coated balloon angioplasty. Patients with Rutherford Clinical Category Score of 1-5, willing and capable of complying with all follow-up evaluations at the specified times, aged ≥18 years, and providing written informed consent prior to the study procedures were eligible for trial participation. Exclusion criteria were contraindications, hypersensitivity to contrast material/device material, uncontrollable hypercoagulable condition or refusal of blood transfusion, life expectancy of less than 12 months, pregnant, not taking adequate contraceptives or nursing, surgical or endovascular procedure of the target vessel within 14 days prior to the index procedure, planned surgical intervention or endovascular procedure within 30 days after the index procedure, currently participating in a study which may interfere, co-morbid condition which precludes safe percutaneous intervention, previous peripheral bypass affecting the target vessel, chronic renal insufficiency with creatinine >2.5 mg/L, and unable or unwilling to receive dual anti-platelet therapy. The intervention group (n=30) underwent a photoablation (laser atherectomy) procedure followed by drug-coated balloon angioplasty. The control group (n=31) underwent PTA followed by drug-coated balloon angioplasty. The follow-up duration was 24 months. The study reported the following relevant outcome measures: target lesion stenosis, primary patency, target lesion revascularization, quality of life, and mortality.

Cai (2019) performed a single center, prospective randomized controlled trial to compare the therapeutic effects of directional atherectomy combined with drug-coated balloon angioplasty with drug-coated balloon angioplasty alone in the treatment of femoropopliteal arteriosclerosis obliterans. Patients who signed an informed consent form, with femoropopliteal artery stenosis >70% (revealed by digital subtraction angiography), or occlusion with unobstructed vascular inflow, with at least a vessel runoff, with good compliance and regular follow-up were eligible for trial participation. Exclusion criteria were cerebrovascular diseases less than half a year, arterial thrombosis, abnormal liver function (serum creatinine >176 micromole/L), contraindications on paclitaxel, antiplatelet or anticoagulation, abnormal protein C, protein S, and antithrombin III, abnormal number of platelets and lower fibrinogen, unsatisfactory control of blood pressure, blood glucose and lipid, inability to quit smoking completely, and poor compliance. In total, 94 patients were eligible and received the allocated intervention. Those patients were randomized into two groups. The intervention group (n=45) underwent directional atherectomy combined with drug-coated balloon angioplasty. The control group (n=49) underwent drug-coated balloon angioplasty alone. The duration of the follow-up was 24 months after endovascular interventions. The study reported the following relevant outcome measures: patency/restenosis (at twelve and 24 months), re-intervention, amputation, and mortality. 

Dattilo (2014) performed a multicenter, prospective, randomized pilot study to compare treatment results of orbital atherectomy versus balloon angioplasty for calcified femoropopliteal disease. Patients who were eighteen years or older, who had peripheral arterial disease with Rutherford class 2-4 symptoms and de novo FP lesions of at least 70% stenosis with fluoroscopically visible calcium, who gave informed consent, and had at least one patent run-off vessel, were eligible for trial participation. Exclusion criteria were An anticipated life span of less than 1 year, known allergy to heparin, aspirin, and clopidogrel, or sensitivity to contrast media, chronic renal failure, cardiac arrhythmias, congestive heart failure exacerbation, and myocardial infarction. In total, 50 patients were eligible and received the allocated intervention. The intervention group (n=25) underwent vessel preparation utilizing orbital atherectomy combined with balloon angioplasty. The control group (n=25) underwent balloon angioplasty alone. The duration of the follow-up was 12 months. The study reported the following relevant outcome measure: patency/restenosis.

Zeller (2017) performed a multicenter randomized pilot trial to estimate the effect of directional atherectomy before drug-coated balloons to facilitate the development of future end point-driven randomized studies. Patients with an RCC of 2-4, who were eighteen years or older, with a target lesion of ≥70% de novo stenosis or restenosis or occlusion in the SFA and/or popliteal artery, who had a target lesion length of 7-15 cm, and who had a reference vessel diameter of 4-7 mm were eligible for trial participation. Exclusion criteria were surgical or endovascular procedure of the target vessel within 14d before the index procedure, planned intervention within 30d after the index procedure, had ≥2 lesions that required treatment in the target limb (not including the iliac arteries), had a target lesion with an occluded segment ≥5 cm in length, had in-stent restenosis of the target lesion or restenosis of the target lesion after previous treatment with a drug-coated balloon, had an acute intraluminal thrombus within the target lesion, had an aneurysmal target vessel. In total, 102 patients were eligible and received the allocated intervention. The intervention group (n=48) underwent directional atherectomy combined with drug-coated balloon angioplasty. The control group (n=54) underwent drug-coated balloon angioplasty alone. The duration of the follow-up was 1 year. The study reported the following relevant outcome measures: patency/restenosis, re-intervention, amputation, and mortality.

Tepe (2021) performed a randomized controlled trial to compare short-term outcomes in patients with femoropopliteal artery calcification receiving vessel preparation with intravascular lithotripsy or percutaneous transluminal angioplasty prior to drug-coated balloon. Patients with symptomatic leg claudication or rest pain (Rutherford class 2 to 4) and angiographic evidence of at least 70% stenosis within the superficial femoral or popliteal artery, lesion length up to 180 mm (up to 100 mm for chronic total occlusion), reference vessel diameter 4 to 7 mm, and moderate or severe calcification were eligible for trial participation. Exclusion criteria were not reported in the study. In total, 306 patients were eligible and received the allocated intervention. The intervention group (n=153) underwent intravascular lithotripsy combined with drug-coated balloon angioplasty. The control group (n=153) underwent percutaneous transluminal angioplasty combined with drug-coated balloon angioplasty. The follow-up duration was 30 days. The study reported the following relevant outcome measures: re-intervention and mortality.

Table 1. Study characteristics.

Results

Freedom from binary restenosis/patency (critical)

One year

Four studies reported the outcome measure freedom from binary restenosis or primary patency at twelve months follow-up (Böhme, 2021; Cai, 2019; Dattilo, 2015; Zeller, 2017).

In total, 95 of 146 patients (65.1%) who underwent vessel preparation were free from restenosis at twelve months, compared with 105 of 151 patients (69.5%) who did not undergo vessel preparation. This resulted in a pooled risk ratio of 1.01 (95% CI 0.89 to 1.15), in favor of the patients who underwent vessel preparation (Figure 1). This difference is not considered clinically relevant.

Figure 1. Freedom from restenosis/primary patency at 12 months

Z: p-value of overall effect; df: degrees of freedom; I2: statistical heterogeneity; CI: confidence interval.

Two years

Two studies reported primary patency at 24 months (Böhme, 2021; Cai, 2019).

In total, 10 of the 18 patients (55.6%) who underwent vessel preparation had primary patency at 24 months, compared with 11 of the 20 patients (55.0%) who did not undergo vessel preparation (Böhme, 2021). This resulted in a risk ratio of 1.01 (95% CI 0.57 to 1.79), in favor of the patients who underwent vessel preparation. This difference is not considered clinically relevant.

In total, 30 of the 45 patients (66.7%) who underwent vessel preparation had primary patency at 24 months, compared with 27 of the 49 patients (55.1%) who underwent no vessel preparation (Cai, 2019). This resulted in a risk ratio of 1.21 (95% CI 0.87 to 1.68), in favor of the patients who underwent vessel preparation. This difference is not considered clinically relevant.

Reintervention based on symptomatic restenosis (critical)

One year

Four studies reported the outcome measure reintervention based on symptomatic restenosis (Böhme, 2021; Cai, 2019; Tepe, 2021; Zeller, 2017).

In total, 10 of 268 patients (3.7%) who underwent vessel preparation underwent reintervention, compared with 12 of 282 patients (4.3%) who did not undergo vessel preparation. This resulted in a pooled risk ratio of 0.92 (95% CI 0.41 to 2.07), in favor of the patients who underwent vessel preparation (Figure 2). This difference is not considered clinically relevant.

Figure 2. Reintervention based on symptomatic restenosis

Z: p-value of overall effect; df: degrees of freedom; I2: statistical heterogeneity; CI: confidence interval.

Two years

One study reported the outcome measure re-intervention based on symptomatic restenosis at two years (Böhme, 2021). In total, 8 of the 22 patients (36.4%) who underwent vessel preparation underwent re-intervention, compared with 7 of the 25 patients (28.0%) who did not undergo vessel preparation. The risk ratio was 1.30 (95% CI 0.56 to 3.00), in favor of the patients who did not undergo vessel preparation. This difference is considered clinically relevant.

Quality of life (important)

One of the studies reported the outcome measure health-related quality of life measured by EQ-5D at one year and at two years (Böhme, 2021).

One year

At one year, the patients who underwent vessel preparation (n=30) had a mean QoL score of 64.46 (SD ± 20.7), compared with a mean QoL score of 68.71 (SD ± 22.5) for the patients who did not undergo vessel preparation (n=31). The mean difference was -4.25 (95% CI -15.09 to 6.59), in favor of the patients who did not undergo vessel preparation. This difference is not considered clinically relevant.

Two years

At two years, the patients who underwent vessel preparation (n=30) had a mean QoL score of 61.84 (SD ± 18.57), compared with a mean QoL score of 68.36 (SD ± 23.06) for the patients who did not undergo vessel preparation (n=31). The mean difference was -6.52 (95% CI -17.01 to 3.97), in favor of the patients who did not undergo vessel preparation. This difference is not considered clinically relevant.

Amputation (important)

Two studies reported the outcome measure amputation (Cai, 2019; Zeller, 2017).

Both Cai (2019) and Zeller (2017) reported limb amputation (treated limb). In both studies, no limb amputations were performed in the group of patients who underwent vessel preparation and in the group of patients who did not undergo vessel preparation. Therefore, no risk ratio could be calculated.

Complications (important)

Dissections

Four studies reported the outcome measure dissections or flow-limiting dissections (Cai, 2019; Dattilo, 2014; Tepe, 2021; Zeller, 2017).

In total, 37 of the 276 patients (13.4%) who underwent vessel preparation suffered from dissection, compared with 84 of the 278 patients (30.2%) who did not undergo vessel preparation. This resulted in a pooled risk ratio of 0.36 (95% CI 0.20 to 0.68), in favor of the patients who underwent vessel preparation (Figure 3). This difference is considered clinically relevant.

Figure 3. Complications - Dissections

Z: p-value of overall effect; df: degrees of freedom; I2: statistical heterogeneity; CI: confidence interval.

Perforations

Three studies reported the outcome measure perforations (Dattilo, 2014; Tepe, 2021; Zeller, 2017).

In total, 2 of the 238 patients (0.8%) who underwent vessel preparation suffered from perforation, compared with 1 of the 233 patients (0.4%) who did not undergo vessel preparation. This resulted in a pooled risk ratio of 1.20 (95% CI 0.05 to 26.65), and the risk difference was 0.00 (95% CI -0.02 to 0.03), in favor of the patients who did not undergo vessel preparation (Figure 4). This difference is not considered clinically relevant. 

Figure 4. Complications - Perforations

Z: p-value of overall effect; df: degrees of freedom; I2: statistical heterogeneity; CI: confidence interval.

Mortality (important)

Four studies reported the outcome measure mortality (Böhme, 2021; Cai, 2019; Tepe, 2021; Zeller, 2017).

In total, 4 of the 268 patients (1.5%) who underwent vessel preparation died, compared with 4 of the 282 patients (1.4%) who did not undergo vessel preparation. This resulted in a pooled risk ratio of 1.30 (95% CI 0.30 to 5.58), and a pooled risk difference of -0.00 (95% CI -0.01 to 0.01), in favor of the patients who did not undergo vessel preparation (Figure 5). This difference is not considered clinically relevant.

Figure 5. Mortality

Z: p-value of overall effect; df: degrees of freedom; I2: statistical heterogeneity; CI: confidence interval.

Level of evidence of the literature

The level of evidence for all outcomes was based on randomized controlled trials and therefore started high.

Freedom from binary restenosis/primary patency (critical)

One year

The level of evidence regarding the outcome measure freedom from binary restenosis/primary patency at one year was downgraded by one level to MODERATE due to study limitations (risk of bias, -1).

Two years

The level of evidence regarding the outcome measure freedom from binary restenosis/primary patency at two years was downgraded by two levels to LOW due to study limitations (risk of bias, -1), and due to the wide confidence intervals indicating large uncertainty of the reported effect size (imprecision, -1).

Re-intervention based on symptomatic restenosis (critical)

One year, two years

The level of evidence regarding the outcome measure re-intervention at one year and two years was downgraded by three levels to VERY LOW due to study limitations (risk of bias, -1), and due to the wide confidence intervals indicating large uncertainty of the reported effect size (imprecision, -2).

Quality of life (important)

One year, two years

The level of evidence regarding the outcome measure quality of life at one year and two years was downgraded by two levels to LOW due to study limitations (risk of bias, -1), and due to the wide confidence intervals indicating large uncertainty of the reported effect size (imprecision, -1).

Amputation (important)

The level of evidence regarding the outcome measure amputation was downgraded by three levels to VERY LOW due to no events reported leading to large uncertainty (imprecision, -3).

Complications (important)

Dissections

The level of evidence regarding the outcome measure complications (dissections) was downgraded by one level to MODERATE due to study limitations (risk of bias, -1).

Perforations

The level of evidence regarding the outcome measure complications (perforations) was downgraded by three levels to VERY LOW due to study limitations (risk of bias, -1), and due to the wide confidence intervals indicating large uncertainty of the reported effect size (imprecision, -2).

Mortality (important)

The level of evidence regarding the outcome measure mortality was downgraded by two levels to LOW due to the wide confidence intervals indicating large uncertainty of the reported effect size (imprecision, -2).

A systematic review of the literature was performed to answer the following question: What are the benefits and harms of treatment with vessel preparation in combination with PTA/stent in comparison with a PTA/stent alone in patients with peripheral arterial disease (femoro-popliteal injury)?

P patients: Patients with PAV (femoro-popliteal injury)

I intervention: Vessel preparation + PTA/stent

C control: PTA/stent

O outcome measure: Mortality, freedom from binary restenosis/patency, reintervention based on symptomatic restenosis, quality of life, amputation, complications

Relevant outcome measures

The guideline development group considered patency/restenosis and re-intervention based on symptomatic restenosis as critical outcome measures for decision making; and quality of life, amputation, complications and mortality as important outcome measures for decision making.

The working group did not define the outcome measures listed above a priori, but used the definitions used in the studies.

The working group defined 25% as a minimal clinically (patient) important difference for dichotomous outcomes (relative risk ≤0.80 or ≥1.25), and 10% of the maximum score for quality of life.

Search and select (Methods)

The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms until 15 April 2024 (update after 6 July 2022). The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 36 hits. The original systematic literature search on 6 July 2022 resulted in 321 hits. Studies were selected based on the following criteria: systematic reviews and randomized controlled trials in patients with PAV (femoropopliteal injury) comparing vessel preparation + PTA or stent with PTA or stent. Fifteen studies were initially selected based on title and abstract screening. After reading the full text, ten studies were excluded (see the table with reasons for exclusion under the tab Methods), and five studies were included.

Results

Five studies were included in the analysis of the literature. Important study characteristics and results are summarized in the evidence tables. The assessment of the risk of bias is summarized in the risk of bias tables.