A Critical View of the Peripheral Atherectomy Data in the Treatment of Infrainguinal Arterial Disease

Abstract: Background. Revascularization of the peripheral arteries remains technically challenging. By decreasing the volume of the atherosclerotic plaque, debulking procedures may confer superior primary patency after revascularization. Aims. To assess the impact of atherectomy on primary patency rates at 12 months compared to balloon angioplasty and/or stent placement alone in patients with infrainguinal arterial disease. Methods. A database search for “directional,” “orbital,” “rotational,” and “laser atherectomy” in peripheral arterial disease (PAD) was performed. Studies were screened according to the STROBE (Strengthening the Reporting of Observational studies in Epidemiology) critical appraisal tool and summarized by population, methodology, and outcomes (primary patency and major adverse events). Results. Only two randomized studies were found. Most of the data were obtained from single-arm studies and registries. The primary patency with directional atherectomy approaches 60% at 12 months as a stand-alone technique, whereas orbital atherectomy in conjunction with balloon angioplasty and stenting achieved primary patency rates of 90%. Laser atherectomy is universally employed with balloon angioplasty and stenting for in-stent restenosis lesions with a primary patency rate of 64%. Although there are data for the safe use of rotational atherectomy, robust data to support its effectiveness are lacking. The combination of drug-coated balloons and atherectomy for the treatment of heavily calcified lesions in patients with critical limb ischemia is under evaluation. Conclusion. Despite the successful procedural outcomes reported in clinical registries, the available data do not support the use of atherectomy alone in PAD. Larger randomized controlled studies are warranted to define its role in contemporary endovascular practice. 

J INVASIVE CARDIOL 2014;26(1):22-29

Key words: directional atherectomy, orbital atherectomy, rotational atherectomy, laser atherectomy, claudication, critical limb ischemia

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It is estimated that within 2 years of an initial revascularization procedure to treat peripheral arterial disease (PAD), nearly 20% of patients will require either a second interventional procedure or an amputation.¹ Even more concerning is that approximately one-third of these amputees will probably lose the contralateral leg in the next 2 years, and approximately one-half of this population will be at continued increased risk of death within 5 years.² In the landmark Bypass versus Angioplasty in Severe Ischemia of the Leg (BASIL) study, which randomized 452 patients with severe limb ischemia to surgical-bypass first or angioplasty-first strategy, angioplasty alone was clinically equivalent to the “gold standard” of surgical bypass in the treatment of critical limb ischemia (CLI), unless the individual’s life expectancy was greater than 2 years.³ Since the publication of the BASIL study, endovascular therapy has emerged as the therapeutic option of choice in patients with infrainguinal PAD regardless of the presence of CLI.⁴ This is likely related to the lower perioperative morbidity seen with angioplasty compared to surgical bypass at 30 days (41% in the angioplasty arm vs 57% in the surgical arm of the BASIL study). Over the course of the last decade, multiple studies and analyses have highlighted the advantages and limitations of the endovascular treatment of PAD.^5-7 Initial therapeutic efforts via percutaneous transluminal angioplasty (PTA) are hampered by the occurrence of arterial wall dissection, perforation, elastic recoil, distal embolization, or acute thrombotic occlusion. As such, PTA often requires provisional stent deployment in about 10%-40% of cases (ie, bail-out stent placement). However, the rates of vessel reocclusion after PTA can be as high as 30% even when stenting is performed.⁵ In this scenario, the use of PTA alone has declined from 35% to 30%, and the use of stents alone (or in combination with other endovascular techniques) has increased from 28.2% to 39.2% according to Medicare data from 1999 to 2005.⁸ In that regard, newer generations of nitinol self-expanding stents and drug-coated balloons (DCB) are currently undergoing clinical trials. Preliminary data from those trials have shown promising results in improving primary patency and decreased vessel reocclusion.⁹ Currently, the spectrum of endovascular therapies includes the use of balloon angioplasty alone (with plain balloon or DCB), primary or ad hoc implantation of plain or drug-eluting nitinol stents, use of “special-design” stents such as interwoven nitinol or polytetrafluoroethylene (PTFE)-covered stents (also called “stent-grafts”), and plaque modification by means of a variety of debulking (ie, atherectomy) devices. Atherectomy is used to facilitate low-pressure balloon inflation as a stand-alone therapy, or to prepare the vessel prior to stent placement. Atherectomy also has the theoretical advantage of protecting side branches by minimizing plaque shift. A disadvantage of atherectomy is the risk of debris embolization to the distal vasculature, and thus the use of embolic protection device is recommended. Four different atherectomy device types are available for use: directional, rotational, orbital (or 360°), and excimer laser. Atherectomy has the potential to decrease the plaque burden and thus has been suggested to be suitable for the treatment of densely calcified plaques.⁷ In that regard, atherosclerotic plaques treated with atherectomy have been studied with intravascular ultrasound. Three different types of atherosclerotic plaques have been described: fibrous, fibro-fatty, or calcified.^10,11 Contrary to initial beliefs, the TRUE (Tissue Removal by Ultrasound Evaluation) study showed that despite a significant reduction in the fibrotic and fibro-fatty volume of the plaque, no effect was seen in either the necrotic core or the dense calcium components of the plaque. Importantly, the TRUE study demonstrated an 11.8% decrease in the plaque volume, but no variation in the overall volume of the vessel was seen, indicating the benefit of atherectomy in plaque reduction.¹⁰ The purpose of this review is to critically appraise the reported outcomes of different atherectomy techniques and devices in the treatment of infra-inguinal disease.

Methods

A multilingual database search was performed from January 1980 to January 2013 in NLM PubMed, Google Scholar, EMBASE, and LILACS. Specific details from clinical trials were obtained from online resources, such as clinicaltrials.gov or from the company-sponsored study website, if available. Additionally, abstracts from endovascular and interventional scientific sessions (TCT, VIVA, SCAI, Leipzig Interventional Course, ISET, CRT, and ACC) were also screened from January 2010 to January 2013. Medical subject heading terms employed in the search included: peripheral arterial disease; atherectomy; excimer laser atherectomy; rotational atherectomy; directional atherectomy; orbital atherectomy; balloon angioplasty; stent; drug-eluting stents; nitinol stents; Jetstream; Phoenix; SilverHawk; TurboHawk; Diamondback 360°; ClirPath; Turbo Elite; and drug-coated balloons. Initially, we sought to screen studies by the experimental design assessing internal and external validity. However, given the scarcity of randomized control trials in the field, we decided to also include observational data from single-arm registries and case series. Studies were screened according to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement.¹² This tool consists of 32 items in reference to the title, abstract, introduction, methods, results, and discussion sections of the articles. As such, STROBE facilitates the critical appraisal and interpretations of the studies by readers. Selected studies were then aggregated by different atherectomy techniques. Data extracted from the studies included demographics, characteristics of the treated lesions, interventional and control arms (if applicable), endpoints such as primary patency and target lesion revascularization (both at 1 year of follow-up), and major adverse events including amputation and death at 1 year of follow-up. Categorical data are presented as a number of events or percentages. Continuous data are presented as mean and standard deviation, unless otherwise stated.

Results

Our search resulted in 385 indexed references, 509 abstracts, and 32 scientific meeting presentations. Following our screening process, we included 2 randomized studies, 10 single-arm studies, 1 registry, and 1 case series. It is important to highlight that the review of the published clinical series and registries was notable for a paucity of head-to-head comparisons of different atherectomy techniques. Many studies were small in size, were investigator-initiated, and used angioplasty alone (without adjunctive stent placement) as the control. Additionally, many studies were supported by the device manufacturer. However, only studies monitored by an independent board were included in an effort to minimize bias and establish confidence in the data results. We present the available data categorized by different atherectomy techniques with an emphasis on study design, as well as the primary patency rates and major adverse events after treatment as reported. Also, we provide preliminary information about ongoing trials as well as future trials. 

Discussion

Directional atherectomy. Directional atherectomy involves the resection of the atherosclerotic plaque with a cutting device in the longitudinal plane.⁶ There are currently two Food and Drug Administration (FDA)-approved devices for directional atherectomy: SilverHawk and TurboHawk (Covidien). The difference between the two devices is the number of contoured inner blades. SilverHawk has one inner blade, whereas TurboHawk has four inner blades and as such favors more plaque removal per pass (Figure 1). A variant of this device to treat heavily calcified lesions is the RockHawk device (Covidien). This device possesses an extra burr on the rotating blade to enhance its cutting action. However, one of the major disadvantages is the high likelihood of distal embolization, and therefore the use of an embolic protection device is recommended.¹³ The TALON (Treating Peripherals with SilverHawk: Outcomes Collection) registry included 601 patients treated with a SilverHawk atherectomy device in addition to provisional PTA or stent. Eighty-seven percent of the treated lesions were de novo and 12.7% were restenotic vessels. Additionally, 65% of the lesions showed moderate-severe calcification and 26.8% were total occlusions. The primary patency at 1 year of follow-up was 80%. PTA was performed in 26.7% of the cases and 6.3% of the cases received stents.¹⁴ Indeed, subsequent clinical series with SilverHawk atherectomy have shown variables rates in the primary patency ranging from 54% to 84% both in native vessels with de novo intervention^15-17 and in vessels with in-stent restenosis.^18-20 The DEFINITIVE-LE (Determination of Effectiveness of the SilverHawk Peripheral Plaque Excision System [Silverhawk Device] for the Treatment of Infrainguinal Vessels/Lower Extremities) study is the largest multicenter study of directional atherectomy. Results of this study have been presented at scientific meetings, but are yet to be published.²¹ The study enrolled 799 claudicants and critical limb ischemia patients for treatment with a SilverHawk atherectomy device. Slightly more than one-half of the patient population was comprised of diabetics (53%). Severely calcified lesions, in-stent restenosis, and aneurysmal target vessel were excluded. The primary patency was determined by duplex ultrasound peak systolic velocity ratio of <2.4. The authors reported a primary patency rate of 78% in the claudicant cohort and 71% in the critical limb ischemia group at 1 year of follow-up (Table 1). Notably, there was no statistical difference in arterial patency between the diabetic and non-diabetic patients. There was an improvement in the walking distance in about 30% of patients in the entire cohort. However, it is worth noting that this was a single-arm study, and that atherectomy was associated with a 3.8% distal embolization rate and a 5.3% rate of vessel perforation. Furthermore, 3% of the patients received provisional stenting. A follow-up study has been designed to investigate the use of embolization protection devices during atherectomy. This study is called DEFINITIVE Ca⁺⁺ and is currently enrolling patients.²² The registry data of directional atherectomy as a stand-alone therapy suggest a primary patency rate of at least 60%; however, it must be emphasized that external validity of the data in these studies is often lacking. 

Rotational atherectomy. Rotational atherectomy devices typically employ a high-speed rotating cutting blade (or “burr”) coated with abrasive material such as microscopic diamond particles. These devices utilize the principle of the differential cutting to act upon the atheroma layers while preserving the structure of the elastic tissue wall. The atherosclerotic material that is removed from the vessel wall (5-10 µm) is dispersed into the distal circulation, and is ultimately cleared by phagocytosis of the resident cells.⁷ Existing rotational atherectomy devices include: the Bayer Pathway PV system (currently Jetstream; Pathway Medical Technologies), and the Phoenix atherectomy catheter (AtheroMed; Figure 1). The multicenter Pathway PVD trial was a proof-of concept study that demonstrated the safety of the Jetstream device in 172 patients, 42% of whom were diabetics. The periprocedural complication rate in this study was low (1%). After 1 year of follow-up, the Rutherford class had improved from a mean of 3.0 to 1.5 for the entire cohort. However, 38.2% of the patients had evidence of vessel restenosis, and 26% of the patients underwent repeat target lesion revascularization (TLR).²³ A major limitation of the study is that the majority of lesions were short, with a mean length of 2.7 cm. The Pathway PV device has also been used in the treatment of in-stent restenosis in 33 patients with infrainguinal lesions. In this clinical series, the authors also utilized adjunctive PTA and reported 67% of freedom in TLR at 1 year of follow-up.²⁴ There are two different types of Jetstream device in use: Jetstream Navitus and Jetstream G3 SF. The latter device has a smaller burr diameter, and is specifically designed for below-the-knee lesions.²⁵ The Navitus device is currently being tested for treatment of in-stent restenosis in the JET study (Safety and Effectiveness of JetStream Atherectomy in Femoropopliteal In-Stent Restenotic Lesions: A Prospective Registry).²⁶ A post-market registry is also in the process of collecting data.²⁷ The Phoenix atherectomy device is still under the investigational exemption category. The EASE (Endovascular Atherectomy Safety and Effectiveness) study is currently evaluating the safety and short-term efficacy of the Phoenix device (Table 2).²⁸ Based on the paucity of data, it is still premature to support rotational atherectomy as a stand-alone procedure.

Orbital atherectomy. This system employs a 360° rotational device with a diamond-coated crown that orbits eccentrically within the vessel contour.²⁹ It is hypothesized that circumferential plaque removal by the device may be associated with better outcomes following low-pressure balloon angioplasty by improving vessel compliance and lowering rates of stent use (due to fewer dissections).^30,31 The only available orbital atherectomy device is the CSI Diamondback Orbital atherectomy system (Cardiovascular Systems, Inc). Current versions include the Predator 360° and the Stealth 360° PAD system. The first-in-human experience was in infrapopliteal lesions in the OASIS (Orbital Atherectomy System for the Treatment of Peripheral Vascular Stenosis) study. OASIS showed 90% procedural success and 1.6% TLR at 6 months of follow-up (Table 3).³² Adjunctive therapy was needed in 41% of the cases and consisted of PTA (39.3%) and stenting (2.5%). Subsequently, the CONFIRM registry prospectively enrolled a total of 3135 patients encompassing 4700 lesions and testing the three generations of orbital atherectomy devices in a real-world population.³³ As a group, the CONFIRIM series showed that orbital atherectomy followed by low-pressure balloon inflations (5.4-5.9 atm) was safe, and was associated with a low rate of provisional stenting (3.8%-5.8%). The CALCIUM 360° (Comparison of Orbital Atherectomy Plus Balloon Angioplasty vs Balloon Angioplasty Alone in Patients with Critical Limb Ischemia) trial compared the combination of orbitalatherectomy with PTA versus PTA-alone in 50 patients with Rutherford class 4-6 and heavily calcified popliteal or infrapopliteal arteries.³⁴ The primary patency rate in the orbital atherectomy with PTA arm was 93% compared to 82% in the PTA-only group. The number of complications was also lower in the combination therapy group (dissection, 3.4%; perforation, 0%; and embolization, 0%) compared with the PTA-only arm (dissection, 17.1%; perforation, 2.8%; and embolization, 2.8%). Importantly, provisional stenting was needed in 7% in the combined arm and in 14% in the PTA-only group. The COMPLIANCE 360° (Comparing Balloon Angioplasty to Diamondback 360° Orbital Atherectomy System in Calcified Femoropopliteal Disease) study employed a similar strategy in femoropopliteal vessels and achieved 72.7% freedom from TLR at 6 months with the combination therapy as compared with the PTA-only group (freedom from TLR, 8.3%) as well as lower balloon inflation pressures (3.9 atm for the combination therapy vs 9.1 atm in the PTA-only group; P<.001).³⁵

Excimer laser atherectomy. This technique utilizes laser to remove atherosclerotic plaque by “photoablation” without damaging the surrounding tissue.³⁶ The device consists of a fiber-optic catheter (in various sizes) that attaches to a console. Laser atherectomy has been used for both de novo and restenotic disease in the infra-inguinal vasculature. It has also been utilized to cross total chronic occlusions when wire passage is not possible. The major limitations to its use include a relatively low gain in the luminal area that is achieved using only the catheter, limited efficacy in the treatment of heavily calcified vessels, and the overall cost of the system. The Turbo-Booster/Turbo-Elite laser catheter (Spectranetics) was studied in the CELLO (CliRpath Excimer Laser System to Enlarge Lumen Openings) registry. The study recruited 65 patients with a mean lesion of 5.4 cm and showed a primary patency of 54% with a freedom from TLR of 76.9% at 1 year of follow-up (Table 4).³⁷ Subsequently, laser atherectomy in conjunction with placement of PTFE-covered stents to treat femoropopliteal artery in-stent restenosis was investigated in the SALVAGE (Prospective, Multicenter Trial to Evaluate the Safety and Performance of Spectranetics Laser with Adjunct PTA and Gore Viabahn Endoprosthesis for theTreatment of SFA ISR) trial.³⁸ In this study of 27 patients, the procedural success rate was 100%, and the observed primary patency was 47%. A larger study was initially planned, but the FDA called into question the safety of the use of excimer laser within nitinol stents. The PATENT (Photo-Ablation using the TURBO-Booster and Excimer Laser for In-Stent Restenosis Treatment) registry was a similar study that enrolled 90 patients with in-stent restenosis who were treated using laser atherectomy with PTA or using PTA alone.³⁹ The primary patency rate was 64% in the laser atherectomy with PTA group versus 34% in the PTA-only group at 1 year of follow-up. Additionally, freedom for TLR was 52% at 1 year of follow-up in the combination therapy. Based on these results, the EXCITE-ISR (Photo-Ablation using the TURBO-Booster and Excimer Laser for In-Stent Restenosis Treatment) registry will enroll 350 patients with nitinol in-stent restenosis to test the superiority of the combined treatment versus PTA only in restenotic lesions.⁴⁰ Excimer laser atherectomy was used in patients with critical limb ischemia in the LACI (Laser Angioplasty for Critical Limb Ischemia) study, which included 145 patients with critical limb ischemia who were poor candidates for surgical revascularization (Rutherford class 4-6). The use of the CliRpath device resulted in a limb salvage rate of 92% at 6 months. Laser atherectomy was infrequently used as the only therapy in LACI, and was followed by PTA in 96% or nitinol stent deployment in up to 45% of patients.⁴¹ Stoner et al⁴² also reported equivalent rates of limb salvage in chronic limb ischemia patients. Shutze et al⁴³ are currently recruiting patients for a prospective, randomized study that compares laser atherectomy with adjunctive PTA to PTA alone in patients with CLI and tissue loss.

Atherectomy and drug-coated balloons. The advent of DCB has renewed the interest in atherectomy for infrainguinal disease. The rationale behind combining atherectomy and DCB is that removal of plaque facilitates the local delivery of the antiproliferative drug, and optimizes drug delivery to the vessel wall. An initial single-center experience with directional atherectomy (utilizing a distal protection device) and DCB in patients with lifestyle-limiting claudication and critical limb ischemia (n = 30) showed primary patency of 90%, TLR of 10%, and limb preservation of 100% at 1 year of follow-up.⁴⁴ Currently, there are two ongoing randomized phase-II trials that involve treatment with directional atherectomy before use of DCB. The DEFINITIVE-AR (Directional Atherectomy Followed by a PaclItaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency: A Pilot Study of Anti-Restenosis Treatment) will enroll 125 patients and will utilize TurboHawk with paclitaxel-DCB (Cotavance; MEDRAD).⁴⁵ Similarly, the ADCAT (Atherectomy and Drug-Coated Balloon Angioplasty in Treatment of Long Infrapopliteal Lesions) study will enroll 80 patients with CLI (Rutherford class 3-6) to be treated TurboHawk and paclitaxel-DCB.⁴⁶ The PHOTOPAC (Photoablative Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis in In-stent Femoro-popliteal Obstructions) will investigate outcomes following laser atherectomy (Turbo Elite) in combination with a paclitaxel-DCB in 50 patients with in-stent restenosis.⁴⁷ In all of these studies, the control arm will be treated with paclitaxel-DCB only (Table 5). A prospective multicenter observational study aims to compare all FDA-approved devices to treat PAD. The study is called LIBERTY 360° and is currently undergoing enrollment. The study will recruit 1200 patients with Rutherford categories 2-6, with 500 patients in Rutherford class 4-5 and 200 patients with CLI who are already scheduled for amputation. The proposed follow-up period will be 5 years after the last visit.⁴⁸

Study limitations. The data presented above are comprised of a small number of peer-reviewed studies available in print or online. It is important to highlight that much of the information was obtained from single-arm registries and case series which reflects paucity of high-quality, long-term, comparative data regarding the use of atherectomy in the literature. The principal investigators were not directly contacted for this review. The use of newer devices such as those that incorporate imaging modalities (namely optical coherence tomography or intravascular ultrasound) to guide atherectomy, or newer devices that perform aspiration in conjunction with atherectomy (eg, the NightHawk device) was not discussed. Finally, the use of distal protection filters during different types of atherectomy procedures was not covered in this review. 

Conclusion

Atherectomy is the removal of atherosclerotic plaque by excision, abrasion, or ablation during endovascular treatment of PAD. It can be performed as a stand-alone therapy, but most commonly is performed as an adjunct to balloon angioplasty and stent placement. Currently, there are four FDA-approved atherectomy devices on the market; however, there are no data regarding their comparative efficacy and safety. Most of the published evidence supporting their use consists of single-arm observational studies or case series. As a result, the available data do not support the use of atherectomy alone. Additional randomized controlled studies are warranted to establish the efficacy and cost-effectiveness of the various atherectomy techniques, and to define their role in contemporary endovascular practice. 

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