CLINICAL STUDY
Midterm Results of Endovascular Treatment of Superficial Femoral Artery Disease with Biodegradable Stents: Single-Center Experience Roberto Silingardi, MD, Antonio Lauricella, MD, Giovanni Coppi, MD, Emanuele Nicolosi, MD, Stefano Gennai, MD, and Gioacchino Coppi, MD
ABSTRACT Purpose: To assess the midterm efficacy of a biodegradable poly-L-lactic acid (PLLA) stent in the treatment of superficial femoral artery (SFA) occlusive disease. Materials and Methods: Between June 2009 and April 2011, 35 de novo SFA lesions were treated with 43 biodegradable stents. This nonrandomized, retrospective, single-center study included patients with moderate or severe claudication, lowerlimb rest pain, or ischemic ulceration restricted to the toes; symptoms were classified as Rutherford category 2 (48.6%), 3 (37.1%), 4 (8.6%), or 5 (5.7%). The population included 28 men and had a mean age of 71 years (range, 51–81 y). Follow-up included clinical examination and color-flow duplex imaging. Mean follow-up was 38.3 months (range, 30–58 mo). Results: Technical success was reported in all patients (100%). There were no intraoperative or immediate (o 30 d) complications.. During follow-up, one in-stent occlusion and seven in-stent restenoses occurred, all of which were successfully treated with percutaneous transluminal angioplasty. Primary and secondary patency rates were 77.1% and 97.1% at 24 and 36 months, respectively. No stent recoil or stent fracture was encountered. Late follow-up (4 12 mo) by ultrasound confirmed total reabsorption of the stent structures. Clinical improvement (ie, an upward shift of at least two Rutherford categories) was achieved in all 35 patients. Conclusions: Midterm results for biodegradable PLLA stents for atherosclerotic SFA lesions were associated with high technical success and secondary patency rates, without stent recoil and vessel remodeling.
ABBREVIATIONS ABI = ankle brachial index, CFD = color flow duplex, DES = drug eluting stent, PLLA = poly-L-lactic acid, PSVR = peak systolic velocity ratio, PTA = percutaneous transluminal angioplasty, SFA = superficial femoral artery, TASC = TransAtlantic Inter-Society Consensus
Despite encouraging early patency rates in the superficial femoral artery (SFA) with the use of nitinol stents (1,2) and more recently with drug-eluting stents (DESs) (3,4), the permanent metallic structure interacts with surrounding
From the Department of Vascular Surgery, Nuovo Ospedale Civile S. Agostino-Estense, Baggiovara, University of Modena and Reggio Emilia, Via Giardini 1355, 41100 Baggiovara (MO), Italy. Received May 5, 2014; final revision received October 19, 2014; accepted October 24, 2014. Address correspondence to A.L.; E-mail: [email protected] None of the authors have identified a conflict of interest. Table E1 is available online at www.jvir.org. & SIR, 2015 J Vasc Interv Radiol 2015; 26:374–381 http://dx.doi.org/10.1016/j.jvir.2014.10.050
tissue and can cause physical irritation, long-term endothelial dysfunction, or chronic inflammatory reactions (5), resulting in inferior results compared with bypass surgery in the medium and long term (6,7,10,11). The rationale for the implantation of fully biodegradable stents is to initially prevent immediate vascular recoil. Throughout follow-up, the mechanical stiffness reduces, enabling positive vessel wall remodeling. The biodegradable stent is designed to minimize pathophysiologic mechanisms of restenosis through its material properties (8–10). In the long term, the stent should be completely reabsorbed, thereby reducing the likelihood of late restenosis (11). Most biodegradable stent research has been dedicated to coronary arterial treatment (12,13), with limited experience in the treatment of the SFA available in the
Volume 26
’
Number 3
’
March
’
2015
375
literature. In 2005, Biamino et al (14) reported the feasibility and safety of the Igaki–Tamai stent for SFA atherosclerotic disease at a mean follow-up of 6 months (14,15). The present study was designed to retrospectively assess the feasibility of biodegradable stent implantation in the treatment of SFA atherosclerotic disease on immediate and midterm follow-up at a single center.
MATERIALS AND METHODS The treatment center’s institutional review board approved the present observational, retrospective study. Between June 2009 and April 2011, 35 patients (28 men; mean age, 71 y; age range, 51–81 y) with moderate or severe claudication (Leriche–Fontaine classification IIB), lower-limb rest pain, or ischemic ulceration restricted to the extremity of the foot only (Rutherford categories 2–5) (16) were assessed for peripheral endovascular procedures. Patients with moderate or severe claudication underwent endovascular revascularization at their request for improved ambulation and/or quality of life. Patients with rest pain or ischemic ulceration to the extremity of the foot were advised to undergo revascularization. Patient characteristics, comorbidities, and lesion classifications are outlined in Table 1. All patients were preoperatively assessed with color-flow duplex (CFD) imaging. Inclusion criteria for endovascular treatment with biodegradable stents was a de novo SFA symptomatic lesion (Z 60% stenosis or occlusion detected with CFD systolic velocity ratio measurement) with a patent popliteal artery free from significant stenosis (4 50%) and at least one patent tibial artery extending to the foot, as confirmed by angiography. Patients were excluded if
the lesions were 1 cm or less from the femoral bifurcation or 3 cm or less from the proximal margin of the intercondylar fossa, or if the presence of significant stenotic (4 50%) or occlusive disease was noted in the inflow arteries. All vascular lesions were classified according to the recommended standards from the modified TransAtlantic Inter-Society Consensus (TASC) II (7) as type A (single stenosis r 10 cm in length, single occlusion r 5 cm) or type B (multiple stenotic or occlusive lesions each r 5 cm or single stenosis or occlusion r 15 cm not involving the infrageniculate popliteal artery). Lesion characteristics and classifications, arterial measurements, pre- and postoperative ankle brachial index (ABI) measurements, and distal runoff were recorded (Table E1, available online at www.jvir.org). The biodegradable Remedy stent (Kyoto Medical Planning, Kyoto, Japan; Fig 1) is made of a poly-Llactic acid (PLLA) monofilament and decomposes in the presence of oxygen through a series of spontaneous chemical reactions; the PLLA is transformed into carbon dioxide and water, in what is known as the citric acid cycle, over a period of 12–18 months. Radial strength is reduced within 6 months. Radiopaque gold markers, located at the proximal and distal ends of the stent and designed to facilitate identification of the stent extremities during placement, remain within the vessel and are incorporated into the arterial wall. The stent has a standard thickness of 0.24 mm (0.009 inches) and ranges from 36 to 78 mm in length and from 5 to 8 mm in width. The stent is mounted on a standard percutaneous transluminal angioplasty (PTA) balloon catheter fixed with a polytetrafluoroethylene clip positioned at the proximal end of the balloon. Stent
Table 1. Patient Characteristics (N ¼ 35) Characteristic
Value
Age (y) Mean Range
71 51–81
Male sex
28 (80)
Comorbidities Hypertension
30 (85.7)
Hyperlipidemia
21 (60)
Diabetes Current smoker
8 (22.8) 12 (34.3)
CAD
16 (45.7)
Lesion classification Rutherford II
17 (48.6)
Rutherford III
13 (37.1)
Rutherford IV Rutherford V
3 (8.6) 2 (5.7)
Values in parentheses are percentages. CAD ¼ coronary artery disease.
Figure 1. Macroscopic view of the Igaki–Tamai stent, a premounted, balloon-expandable PLLA stent that is also selfexpandable with straight bridges and gold markers at both ends (arrows). The PLLA monofilament (molecular mass, 183 kDa) coil stent is designed in a zigzag helical structure. The PLLA decomposes in the presence of oxygen following implantation, over a period of 12–18 months. (Reproduced with permission from Kyoto Medical Planning).
376
’
Endovascular Treatment of SFA Disease with Biodegradable Stents
deployment is achieved through a balloon-expandable covered sheath system introduced through a 7-F guiding catheter.
Procedural Details All patients were prescribed antiplatelet therapy (acetylsalicylic acid 100 mg) at least 7 days before the planned intervention; 31 patients (88.5%) were already taking this medication. Admittance to the vascular surgery department was scheduled 1 day before treatment. Femoral access and run-in feasibility were assessed with a CFD scan or computed tomographic angiography in doubtful cases, and ABI and vessel measurements were recorded. All endovascular interventions were performed in a dedicated angiographic room equipped with a C-arm (OEC 9800; GE Medical Systems, Waukesha, Wisconsin) and a CFD scanner (AU5; Esaote, Genoa, Italy). All interventions were performed by, or under the supervision of, one senior vascular surgeon (S.R.). Local anesthesia was used exclusively. Access in all cases was achieved from the ipsilateral groin by using a 7-F introducer sheath (Cordis, Miami Lakes, Florida). A standardized endovenous bolus of 5,000 IU of unfractionated heparin was administered systematically, and diagnostic angiography was performed to quantify lesion extent.
Silingardi et al
’
JVIR
Lesions were preferentially crossed with a 0.035-inch hydrophilic guide wire with a J-angled tip (Radifocus M; Terumo, Leuven, Belgium) supported by a 4-F angled angiographic catheter (Radifocus Glidecath Vertebral; Terumo). All stenoses and occlusions were predilated with a 4or 5-mm noncompliant balloon (FoxCross; Abbott Vascular, Santa Clara, California) inflated for 60 seconds at 6–12 atm. Biodegradable stents were then deployed. Postdeployment angioplasty of stents was performed to optimize vessel wall apposition, even for balloon-expandable stents. A noncompliant balloon 1 mm wider than the stent diameter (FoxCross; Abbott Vascular) was inflated for a maximum of 5 seconds (Figs 2, 3). Postinterventional antithrombotic therapy included a dual antiplatelet aggregation regimen with 75 mg clopidogrel and 100 mg acetylsalicylic acid (ASA) per day for 4 weeks, followed by ASA indefinitely. Low molecular weight heparin (enoxaparin 100 IU/kg/d) was administered in the immediate postoperative period for 1 week.
Definitions and Follow-up Technical success was determined as no more than 30% final residual stenosis measured at the narrowest point of the treated segment. Restenosis was defined as greater than a 2.4 peak systolic velocity ratio (PSVR) by CFD (17) or more than 50% stenosis by angiography. PSVR
Figure 2. Angiographic images of a short, severe lesion of the distal SFA before (a) and after (b, c) deployment of the Igaki–Tamai stent. The arrows highlight the location and visibility of the proximal and distal gold markers.
Volume 26
’
Number 3
’
March
’
2015
377
was measured at the stent-implanted site across the treated lesion (Table 2). Patency was defined as the absence of at least 50% recurrent stenosis. Complete occlusions were classified as undetectable signals by
CFD in stent-implanted segments. Asymptomatic restenosis was defined as the documentation of stenosis without clinical relevance with less than a 2.4 PSVR by CFD (17) or less than 50% stenosis by angiography.
Figure 3. Angiographic images of a complex, long lesion of the SFA (a) treated with deployment of three Igaki–Tamai reabsorbable stents (b). Successful revascularization, determined as no greater than 30% final residual stenosis measured at the narrowest point of the treated segment, was achieved as shown on final intraoperative angiography (c). Table 2. Restenosis Rates Determined by CFD Flow Normal
Stenosis (%)
Preoperative
Discharge
1 mo
6 mo
12 mo
18 mo
24 mo
36 mo
0–20
0
32 (91)
30 (86)
25 (71)
25 (71)
32 (91)
32 (91)
30 (86)
PSVR Z 1.33
20–30
0
2
5
3
2
1
1
2
PSVR Z 1.6 PSVR Z 2.1
30–40 40–50
0 0
1 0
0 0
3 4
0 0
2 0
2 0
3 0
PSVR Z 2.4
50–60
0
0
0
0
0
0
0
0
PSVR Z 2.9 PSVR Z 3.4
60–70 70–80
0 3
0 0
0 0
0 0
0 0
0 0
0 0
0 0
PSVR Z 4.0
80–90
5
0
0
0
6
0
0
0
PSVR Z 7.0 No Flow
4 90 Occlusion
7 20
0 0
0 0
0 0
1 1
0 0
0 0
0 0
Values in parentheses are percentages. Test for trend (proportion of cases with normal flow) from discharge to 36 mo: χ2 ¼ 0.191, P ¼ .662. CFD ¼ color-flow duplex, PSVR ¼ peak systolic velocity ratio.
378
’
Endovascular Treatment of SFA Disease with Biodegradable Stents
Stent diameter was calculated as the maximum transverse diameter, defined as the maximum average distance between two opposite points of the hyperechogenic stent scaffold. Vessel diameter was intended from adventitia to adventitia. The measures of the vessel lumen were based on color-flow filling of the vessel lumen detected at CFD (Table 3). The maximum distance of the wall of the treated arterial vessel was recorded in early and midterm followup when the traceability of the stent was much more difficult later during follow-up as a result of progressive reduction of the hyperechogenic structure of the reabsorbing stent (18). Primary patency was defined as the absence of restenosis (Z 50% or PSVR o 2.4) in the target lesion. Primary assisted patency included patients with successful target vessel revascularization, and secondary patency included patients with successful target lesion revascularization. Follow-up included physical assessment, ABI measurements, and CFD at discharge, at 1, 3, and 6 months, and biannually thereafter. Follow-up was categorized according to time intervals: early (r 30 d), midterm (4 30 d but r 6 mo), and late (4 6 mo) follow-up.
Statistical Analysis Patient characteristics are reported as means ⫾ standard deviation for continuous data and as counts and percentages for categoric data. A paired t test and χ2 test for trend proportions were performed to assess the presence of remarkable differences in parameters between preand postoperative stages and during follow-up.
Silingardi et al
JVIR
removal of atheroma and thrombus with preliminary mechanical debulking (Rotarex Mechanical Thrombectomy System; Straub Medical, Wangs, Switzerland), and subsequent PTA with a drug-eluting balloon (Admiral 7 80 mm; Invatec, Frauenfeld, Switzerland; Fig 4). Seven symptomatic in-stent restenoses were successfully treated with PTA (Fig 5). Drug-eluting balloons (Admiral; Invatec) were used in four patients and nitinol stents were used in three patients, two of whom were treated for external iliac stenosis detected at late followup. No further repeat interventions were required throughout the remaining of the follow-up period (Table 4). Primary and secondary patency rates were 77.1% and 97.1%, respectively, at 24 and 36 months. Target lesion revascularization and target vessel revascularization rates were 22.8% and 5.5% at 24 and 36 months, respectively (Table 5). There were no cases of stent recoil or stent fracture during follow-up. A significant increase in hyperechogenicity of the scaffolded segment following stent implantation was noted in all treated lesions at CFD examinations during follow-up. The vessel wall presented hyperechogenic spots corresponding to the stent structure during early and midterm follow-up. A significant reduction in hyperechogenicity was detected in all patients from 12 months. Stent struts were visible on grayscale ultrasound scans in all patients (100%) at 6 months and in 94.3% at 12 months. Stent structure was partially visible in 10
Table 4. Results of SFA Endovascular Treatment with Bioresorbable Stent
RESULTS
Variable
Procedural success was confirmed at intraoperative angiography in 100% of cases. The average procedure time was 45 minutes (range, 20–75 min). No significant perioperative complications were noted (Table 4). All patients completed the scheduled follow-up protocol. The mean clinical follow-up period was 38.3 months (range, 30–58 mo). Asymptomatic restenosis was recorded in 10 patients (28.5%) within 30 days. The patients were not treated and were counseled to adhere strictly to the follow-up schedule. One in-stent occlusion at 12 months was recorded, which was successfully treated with the partial
’
Value
Procedural success
35 (100)
30-d complications
0
Follow-up (mo) Mean
38.3
Range
30–58
Symptomatic intrastent restenosis Time to symptomatic intrastent restenosis (mo) Mean
7 (20) 6.5
Range Intrastent occlusion
5–9 1 (2.8)
Values in parentheses are percentages. SFA ¼ superficial femoral artery.
Table 3. Results of CFD Preoperative and Postoperative Study Preoperative
Postoperative
1 d after Procedure
6 mo
12 mo
24 mo
36 mo
Measurement
(N ¼ 35)
(N ¼ 35)
(N ¼ 35)
(N ¼ 35)
(N ¼ 35)
(N ¼ 35)
(n ¼ 32)
Vessel diameter (mm)
5.2 ⫾ 1.3
5.6 ⫾ 1.3
5.6 ⫾ 1.3
5.6 ⫾ 1.3
5.6 ⫾ 1.3
5.6 ⫾ 1.3
5.6 ⫾ 1.2
Stent diameter (mm) Lumen (mm)
– 1.1 ⫾ 1.1
5.8 ⫾ 0.6 5.4 ⫾ 1.2
5.8 ⫾ 0.6 5.4 ⫾ 1.3
5.9 ⫾ 0.7 5.4 ⫾ 1.2
5.8 ⫾ 0.7 4.3 ⫾ 2.2.
ND 5.4 ⫾ 1.1
ND 5.4 ⫾ 1.0
Values presented as means ⫾ standard deviation. Paired t test, pre- vs postoperative: vessel diameter, P ¼ .207; lumen, P o .001. CFD ¼ color-flow duplex, ND ¼ not detected.
Volume 26
’
Number 3
’
March
’
2015
379
Figure 4. In-stent occlusion was observed at 12 months in the SFA (a) and treated with a partial removal of the in-stent atheroma and thrombus with a debulking technique and drug-eluting balloon angioplasty. Patency of the distal third of the SFA was shown on final intraoperative angiography (b).
patients at 24 months. Stent profile was no longer visible in all 35 cases at 30 months, suggesting complete stent structure reabsorption (Table 3).
DISCUSSION Although some data support the superiority of nitinol stent implantation over balloon angioplasty for atherosclerotic SFA lesions, rates of restenosis, stent thrombosis, and stent fracture remain high (19). DESs were designed in response to these suboptimal results, but DES treatment has been associated with subacute and late stent thrombosis (20). Results from early experiences with sirolimus-eluting stents in the treatment of SFA lesions have not yet proven to be superior to nitinol stents (4), and further studies are currently ongoing. Biodegradable stents represent a new frontier in the field of endovascular treatment for peripheral atherosclerotic lesions (9,10) through temporary vessel wall support and reduced mechanical stiffness over time, thereby reducing the risk of recoil and redefining restenosis rates (17,21,22). The pathophysiologic mechanisms of restenosis are minimized through the degradation of device materials into chemical substances without stimulation of the cell wall
foreign body reactive metabolism. Preliminary results from a dedicated study (unpublished data; ClinicalTrials.gov identifier NCT01403077) have not yet found any correlation between biodegradable stent implantation and any inflammatory cell infiltration or foreign body reaction. The optimal duration before complete absorption of a stent scaffold remains an open question. If this period is too short, the stent will lose radial force too early, threatening vessel patency and recoil. Alternatively, if the period is too long, all the advantages of temporary support are lost. Current indications suggest that optimal positive remodeling with vessel lumen enlargement is achieved following mechanical stent integrity for at least 6 months (23). Stent scaffolds in the present study were still visible at 6 months for all patients. Most biodegradable stent experience has been reported for coronary arterial disease; the first human trial for biodegradable stents (9) was conducted in 25 coronary artery stenotic lesions in 15 patients and showed a restenosis rate of 10.5% at 6 months. Nishio et al (24) confirmed the long-term safety of biodegradable stents 12 years later, reporting clinical outcomes at 10 years for the first 50 patients treated with biodegradable stents for coronary arterial disease. Despite the small sample size, biodegradable stent biocompatibility for human arteries
380
’
Endovascular Treatment of SFA Disease with Biodegradable Stents
Silingardi et al
’
JVIR
Figure 5. (a) Symptomatic in-stent restenosis (arrows) was detected on angiography and successfully treated with drug-eluting balloon angioplasty. Final intraoperative angiography confirmed successful treatment (b).
Table 5. Results of SFA Endovascular Treatment with Bioresorbable Stent Patency
Interval
Primary
Primary Assisted
Secondary
TLR
TVR
1y 2y
29 (82.8) 27 (77.1)
30 (85.7) 28 (80)
34 (97.1) 34 (97.1)
6 (17.1) 8 (22.8)
0 2 (5.71)
3y
27 (77.1)
28 (80)
34 (97.1)
8 (22.8)
2 (5.71)
.556
.535
.990
.557
.212
P value*
Values in parentheses are percentages. SFA ¼ superficial femoral artery, TLR ¼ target lesion revascularization, TVR ¼ target vessel revascularization. n Test for trend.
was confirmed; there were no signs of apparent inflammation or unexpected adverse events, and regular angiographic, intravascular, and clinical findings were highlighted throughout the follow-up. However, as previous experiences with DESs and drug-eluting balloons have shown, results obtained in coronary arteries are not always transferable to other vascular territories. Biamino et al (14) were the first to report endovascular treatment of the SFA with biodegradable stents in a
prospective, nonrandomized, two-center pilot study of 45 patients with TASC B and C lesions. The first phase reported a 6-month symptomatic restenosis rate of 25% (all successfully treated) and asymptomatic restenosis of 18%. No acute or subacute reocclusions were reported. In the second phase, an improved stent was implanted. In 65 patients, two reocclusions and a 28% rate of symptomatic restenosis were reported at 6 months (14). There are many studies currently ongoing that are analyzing the appropriateness of biodegradable stents for SFA. The ESPRIT I trial is currently evaluating the drugeluting bioresorbable vascular scaffold (Abbott Vascular) in 35 patients; this device was developed specifically for the SFA (TASC A lesions) and iliac arteries. A prospective, multicenter trial (unpublished data; ClinicalTrials.gov identifier NCT01403077) dedicated to symptomatic SFA atherosclerosis is currently assessing the efficacy of the Stanza bioresorbable scaffold (480 Biomedical, Watertown, Massachusetts). Standard endpoints are being investigated, along with the acute performance and subsequent stent strut encapsulation and reabsorption according to optical coherence tomography. The recently initiated SPRINT trial (unpublished data; ClinicalTrials.gov identifier NCT02097082) is assessing a drug-eluting version of
Volume 26
’
Number 3
’
March
’
2015
the Stanza scaffold (paclitaxel-eluting bioresorbable scaffold; 480 Biomedical) for de novo SFA lesions. Both trials are still under way, and no official data are available yet. To our knowledge, the present study reports the first midterm results with a PLLA biodegradable stent in SFA atherosclerotic disease, with encouraging results. However, the study has several limitations. This was an observational, single-center, nonrandomized study without a predetermined follow-up period. Late angiography was performed based on clinical indications only, so angiographic patency information was not available for asymptomatic patients. Because of the small patient cohort, statistical significance is difficult to achieve, and, as the significance level was not adjusted for multiple tests, the rates of type I error may be high. Patient selection bias is also inherent, as this study includes patients who were considered for endovascular treatment only. In addition, patient selection for stent placement was made at the discretion of the surgeon directly in the angiographic suite based on angiography, anatomy, and general clinical conditions. This study was carried out in a single center of regional reference, with an established interventional technique, so the results obtained in this series may not be reproducible and may require confirmation from multicenter studies. The midterm results with the use of a biodegradable PLLA stent for atherosclerotic SFA lesions seem promising in terms of low restenosis rates without stent recoil and vessel remodeling and may provide an optimal solution for patients with symptomatic peripheral artery disease. This new technology could open new possibilities in the treatment of femoropopliteal lesions, including the application of different drugs on the stent struts. These results require validation in larger trials that include patients with more complex lesions.
ACKNOWLEDGMENTS The authors thank Dr. Luigi Marcheselli for his statistical data evaluation and Johanna Chester for her editorial and critical review assistance.
REFERENCES 1. Schillinger M, Sabeti S, Loewe C, et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med 2006; 354:1879–1888. 2. Dick P, Wallner H, Sabeti S, et al. Balloon angioplasty versus stenting with nitinol stents in intermediate length superficial femoral artery lesions. Catheter Cardiovasc Interv 2009; 74:1090–1095.
381
3. Lammer J, Bosiers M, Zeller T. First clinical trial of nitinol self-expanding everolimus-eluting stent implantation for peripheral arterial occlusive disease. J Vasc Surg. 2011 Aug; 54(2):394–401. 4. Duda SH, Bosiers M, Lammer J, et al. Drug-eluting and bare nitinol stents for the treatment of atherosclerotic lesions in the superficial femoral artery: long-term results from the SIROCCO trial. J Endovasc Ther. 2006 Dec; 13(6):701–710. 5. Migliavacca F, Petrini L, Massarotti P, et al. Stainless and shape memory alloy coronary stents: a computational study on the interaction with the vascular wall. Biomech Model Mechanobiol. 2004; 2:205–217. 6. Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg 2000; 31:S1–S296. 7. Norgren L, Hiatt WR, Dormandy JA, et al. TASC II Working Group. InterSociety Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007; 43:S1–67. 8. Peuster M, Wohlsein P, Brügmann M, et al. A novel approach to temporary stenting: degradable cardiovascular stents produced from corrodible metal-results 6–18 months after implantation into New Zealand white rabbits. Heart 2001; 86:563–569. 9. Tamai H, Igaki K, Kyo E, et al. Initial and 6-month results of biodegradable poly-L-lactic acid coronary stents in humans. Circulation 2000; 102: 399–404. 10. Tsuji T, Tamai H, Igaki, et al. Biodegradable polymeric stents. Curr Interv Cardiol Rep 2001; 3:10–17. 11. Heublein B, Rohde R, Kaese V, Niemeyer M, Hartung W, Haverich A. Biocorrosion of magnesium alloys: a new principle in cardiovascular implant technology? Heart 2003; 89:651–656. 12. Ormiston JA, Serruys PW, Regar E, et al. A bioabsorbable everolimuseluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial. Lancet 2008; 371: 899–907. 13. Serruys PW, Ormiston JA, Onuma Y, et al. A bioabsorbable everolimuseluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods. Lancet 2009; 373:897–910. 14. Biamino G, Schmidt A, Scheinert D. Treatment of SFA lesions with PLLA biodegradable stents: results of the PERSEUS study. J Endovasc Ther. 2005; 12(Suppl I):5. 15. Vermassen F, Bouckenooghe I, Moreels N, Goverde P, Schroe H. Role of bioresorbable stents in the superficial femoral artery. J Cardiovasc Surg (Torino) 2013 Apr; 54(2):225–234. 16. Rutherford RB, Baker JD, Ernst C, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997; 26:517–538. 17. Moravej M, Mantovani D. Biodegradable metals for cardiovascular stent application: interests and new opportunities. Int J Mol Sci. 2011; 12(7): 4250–4270. 18. Sacks D, Marinelli DL, Martin LG, Spies JB. Reporting standards or clinical evaluation of new peripheral arterial revascularization devices. J Vasc Interv Radiol 2003; 14:395–404. 19. Mewissen MW. Self-expanding nitinol stents in the femoropopliteal segment: technique and mid-term results. Tech Vasc Interv Radiol 2004; 7:2–5. 20. Kuchulakanti PK, Chu WW, Torguson R, et al. Correlates and long-term outcomes of angiographically proven stent thrombosis with sirolimusand paclitaxel-eluting stents. Circulation 2006 Feb 28; 113(8):1108–1113. 21. Tsuji T, Tamai H, Igaki K, et al. Biodegradable stents as a platform to drug loading. Int J Cardiovasc Intervent 2003; 5:13–16. 22. Peeters P, Bosiers M, Verbist J, Deloose K, Heublein B. Preliminary results after application of absorbable metal stents in patients with critical limb ischemia. J Endovasc Ther. 2005 Feb; 12(1):1–5. 23. Onuma Y, Serruys PW. Bioresorbable scaffold: the advent of a new era in percutaneous coronary and peripheral revascularization? Circulation 2011 Feb 22; 123(7):779–797. 24. Nishio S, Kosuga K, Igaki K, et al. Long-term (410 years) clinical outcomes of first-in-human biodegradable poly-L-lactic acid coronary stents: Igaki-Tamai stents. Circulation 2012; 125:2343–2352.
381.e1
’
Endovascular Treatment of SFA Disease with Biodegradable Stents
Table E1 . Lesion Characteristics Characteristic No. of limbs
Value 35
Target artery Superficial femoral artery Surgical approach Anterograde TASC II classification A B Lesion length (mm) Mean
35 (100) 35 (100) 22 (62.8) 13 (37.2) 6.8
Range
2.5–13
Stenosis Occlusion
15 (42.9) 20 (57.1)
Mean stenosis length (cm) Mean Range
7.1 3–13
Mean occlusion length (cm) Mean Range
6.2 2.5–11
Reference vessel diameter (mm)
5.2 ⫾ 1.3
Below-knee runoff 2 vessels
11 (31.4)
3 vessels Preprocedure ABI Postprocedural ABI Number of stents
24 (68.6) 0.53 ⫾ 0.15 0.85 ⫾ 0.15 43
Stent length 36 mm
22 (62.8)
78 mm
21 (37.2)
Stent diameter 5 mm
6 (17.1)
6 mm
14 (40)
7 mm 8 mm
14 (40) 1 (2.9)
Values in parentheses are percentages. Values presented as means ⫾ standard deviation where appropriate. ABI ¼ ankle brachial index, TASC ¼ TransAtlantic Inter-Society Consensus.
Silingardi et al
’
JVIR
Midterm Results of Endovascular Treatment of Superficial Femoral Artery Disease with Biodegradable Stents: Single-Center Experience Roberto Silingardi, MD, Antonio Lauricella, MD, Giovanni Coppi, MD, Emanuele Nicolosi, MD, Stefano Gennai, MD, and Gioacchino Coppi, MD
ABSTRACT Purpose: To assess the midterm efficacy of a biodegradable poly-L-lactic acid (PLLA) stent in the treatment of superficial femoral artery (SFA) occlusive disease. Materials and Methods: Between June 2009 and April 2011, 35 de novo SFA lesions were treated with 43 biodegradable stents. This nonrandomized, retrospective, single-center study included patients with moderate or severe claudication, lowerlimb rest pain, or ischemic ulceration restricted to the toes; symptoms were classified as Rutherford category 2 (48.6%), 3 (37.1%), 4 (8.6%), or 5 (5.7%). The population included 28 men and had a mean age of 71 years (range, 51–81 y). Follow-up included clinical examination and color-flow duplex imaging. Mean follow-up was 38.3 months (range, 30–58 mo). Results: Technical success was reported in all patients (100%). There were no intraoperative or immediate (o 30 d) complications.. During follow-up, one in-stent occlusion and seven in-stent restenoses occurred, all of which were successfully treated with percutaneous transluminal angioplasty. Primary and secondary patency rates were 77.1% and 97.1% at 24 and 36 months, respectively. No stent recoil or stent fracture was encountered. Late follow-up (4 12 mo) by ultrasound confirmed total reabsorption of the stent structures. Clinical improvement (ie, an upward shift of at least two Rutherford categories) was achieved in all 35 patients. Conclusions: Midterm results for biodegradable PLLA stents for atherosclerotic SFA lesions were associated with high technical success and secondary patency rates, without stent recoil and vessel remodeling.
ABBREVIATIONS ABI = ankle brachial index, CFD = color flow duplex, DES = drug eluting stent, PLLA = poly-L-lactic acid, PSVR = peak systolic velocity ratio, PTA = percutaneous transluminal angioplasty, SFA = superficial femoral artery, TASC = TransAtlantic Inter-Society Consensus
Despite encouraging early patency rates in the superficial femoral artery (SFA) with the use of nitinol stents (1,2) and more recently with drug-eluting stents (DESs) (3,4), the permanent metallic structure interacts with surrounding
From the Department of Vascular Surgery, Nuovo Ospedale Civile S. Agostino-Estense, Baggiovara, University of Modena and Reggio Emilia, Via Giardini 1355, 41100 Baggiovara (MO), Italy. Received May 5, 2014; final revision received October 19, 2014; accepted October 24, 2014. Address correspondence to A.L.; E-mail: [email protected] None of the authors have identified a conflict of interest. Table E1 is available online at www.jvir.org. & SIR, 2015 J Vasc Interv Radiol 2015; 26:374–381 http://dx.doi.org/10.1016/j.jvir.2014.10.050
tissue and can cause physical irritation, long-term endothelial dysfunction, or chronic inflammatory reactions (5), resulting in inferior results compared with bypass surgery in the medium and long term (6,7,10,11). The rationale for the implantation of fully biodegradable stents is to initially prevent immediate vascular recoil. Throughout follow-up, the mechanical stiffness reduces, enabling positive vessel wall remodeling. The biodegradable stent is designed to minimize pathophysiologic mechanisms of restenosis through its material properties (8–10). In the long term, the stent should be completely reabsorbed, thereby reducing the likelihood of late restenosis (11). Most biodegradable stent research has been dedicated to coronary arterial treatment (12,13), with limited experience in the treatment of the SFA available in the
Volume 26
’
Number 3
’
March
’
2015
375
literature. In 2005, Biamino et al (14) reported the feasibility and safety of the Igaki–Tamai stent for SFA atherosclerotic disease at a mean follow-up of 6 months (14,15). The present study was designed to retrospectively assess the feasibility of biodegradable stent implantation in the treatment of SFA atherosclerotic disease on immediate and midterm follow-up at a single center.
MATERIALS AND METHODS The treatment center’s institutional review board approved the present observational, retrospective study. Between June 2009 and April 2011, 35 patients (28 men; mean age, 71 y; age range, 51–81 y) with moderate or severe claudication (Leriche–Fontaine classification IIB), lower-limb rest pain, or ischemic ulceration restricted to the extremity of the foot only (Rutherford categories 2–5) (16) were assessed for peripheral endovascular procedures. Patients with moderate or severe claudication underwent endovascular revascularization at their request for improved ambulation and/or quality of life. Patients with rest pain or ischemic ulceration to the extremity of the foot were advised to undergo revascularization. Patient characteristics, comorbidities, and lesion classifications are outlined in Table 1. All patients were preoperatively assessed with color-flow duplex (CFD) imaging. Inclusion criteria for endovascular treatment with biodegradable stents was a de novo SFA symptomatic lesion (Z 60% stenosis or occlusion detected with CFD systolic velocity ratio measurement) with a patent popliteal artery free from significant stenosis (4 50%) and at least one patent tibial artery extending to the foot, as confirmed by angiography. Patients were excluded if
the lesions were 1 cm or less from the femoral bifurcation or 3 cm or less from the proximal margin of the intercondylar fossa, or if the presence of significant stenotic (4 50%) or occlusive disease was noted in the inflow arteries. All vascular lesions were classified according to the recommended standards from the modified TransAtlantic Inter-Society Consensus (TASC) II (7) as type A (single stenosis r 10 cm in length, single occlusion r 5 cm) or type B (multiple stenotic or occlusive lesions each r 5 cm or single stenosis or occlusion r 15 cm not involving the infrageniculate popliteal artery). Lesion characteristics and classifications, arterial measurements, pre- and postoperative ankle brachial index (ABI) measurements, and distal runoff were recorded (Table E1, available online at www.jvir.org). The biodegradable Remedy stent (Kyoto Medical Planning, Kyoto, Japan; Fig 1) is made of a poly-Llactic acid (PLLA) monofilament and decomposes in the presence of oxygen through a series of spontaneous chemical reactions; the PLLA is transformed into carbon dioxide and water, in what is known as the citric acid cycle, over a period of 12–18 months. Radial strength is reduced within 6 months. Radiopaque gold markers, located at the proximal and distal ends of the stent and designed to facilitate identification of the stent extremities during placement, remain within the vessel and are incorporated into the arterial wall. The stent has a standard thickness of 0.24 mm (0.009 inches) and ranges from 36 to 78 mm in length and from 5 to 8 mm in width. The stent is mounted on a standard percutaneous transluminal angioplasty (PTA) balloon catheter fixed with a polytetrafluoroethylene clip positioned at the proximal end of the balloon. Stent
Table 1. Patient Characteristics (N ¼ 35) Characteristic
Value
Age (y) Mean Range
71 51–81
Male sex
28 (80)
Comorbidities Hypertension
30 (85.7)
Hyperlipidemia
21 (60)
Diabetes Current smoker
8 (22.8) 12 (34.3)
CAD
16 (45.7)
Lesion classification Rutherford II
17 (48.6)
Rutherford III
13 (37.1)
Rutherford IV Rutherford V
3 (8.6) 2 (5.7)
Values in parentheses are percentages. CAD ¼ coronary artery disease.
Figure 1. Macroscopic view of the Igaki–Tamai stent, a premounted, balloon-expandable PLLA stent that is also selfexpandable with straight bridges and gold markers at both ends (arrows). The PLLA monofilament (molecular mass, 183 kDa) coil stent is designed in a zigzag helical structure. The PLLA decomposes in the presence of oxygen following implantation, over a period of 12–18 months. (Reproduced with permission from Kyoto Medical Planning).
376
’
Endovascular Treatment of SFA Disease with Biodegradable Stents
deployment is achieved through a balloon-expandable covered sheath system introduced through a 7-F guiding catheter.
Procedural Details All patients were prescribed antiplatelet therapy (acetylsalicylic acid 100 mg) at least 7 days before the planned intervention; 31 patients (88.5%) were already taking this medication. Admittance to the vascular surgery department was scheduled 1 day before treatment. Femoral access and run-in feasibility were assessed with a CFD scan or computed tomographic angiography in doubtful cases, and ABI and vessel measurements were recorded. All endovascular interventions were performed in a dedicated angiographic room equipped with a C-arm (OEC 9800; GE Medical Systems, Waukesha, Wisconsin) and a CFD scanner (AU5; Esaote, Genoa, Italy). All interventions were performed by, or under the supervision of, one senior vascular surgeon (S.R.). Local anesthesia was used exclusively. Access in all cases was achieved from the ipsilateral groin by using a 7-F introducer sheath (Cordis, Miami Lakes, Florida). A standardized endovenous bolus of 5,000 IU of unfractionated heparin was administered systematically, and diagnostic angiography was performed to quantify lesion extent.
Silingardi et al
’
JVIR
Lesions were preferentially crossed with a 0.035-inch hydrophilic guide wire with a J-angled tip (Radifocus M; Terumo, Leuven, Belgium) supported by a 4-F angled angiographic catheter (Radifocus Glidecath Vertebral; Terumo). All stenoses and occlusions were predilated with a 4or 5-mm noncompliant balloon (FoxCross; Abbott Vascular, Santa Clara, California) inflated for 60 seconds at 6–12 atm. Biodegradable stents were then deployed. Postdeployment angioplasty of stents was performed to optimize vessel wall apposition, even for balloon-expandable stents. A noncompliant balloon 1 mm wider than the stent diameter (FoxCross; Abbott Vascular) was inflated for a maximum of 5 seconds (Figs 2, 3). Postinterventional antithrombotic therapy included a dual antiplatelet aggregation regimen with 75 mg clopidogrel and 100 mg acetylsalicylic acid (ASA) per day for 4 weeks, followed by ASA indefinitely. Low molecular weight heparin (enoxaparin 100 IU/kg/d) was administered in the immediate postoperative period for 1 week.
Definitions and Follow-up Technical success was determined as no more than 30% final residual stenosis measured at the narrowest point of the treated segment. Restenosis was defined as greater than a 2.4 peak systolic velocity ratio (PSVR) by CFD (17) or more than 50% stenosis by angiography. PSVR
Figure 2. Angiographic images of a short, severe lesion of the distal SFA before (a) and after (b, c) deployment of the Igaki–Tamai stent. The arrows highlight the location and visibility of the proximal and distal gold markers.
Volume 26
’
Number 3
’
March
’
2015
377
was measured at the stent-implanted site across the treated lesion (Table 2). Patency was defined as the absence of at least 50% recurrent stenosis. Complete occlusions were classified as undetectable signals by
CFD in stent-implanted segments. Asymptomatic restenosis was defined as the documentation of stenosis without clinical relevance with less than a 2.4 PSVR by CFD (17) or less than 50% stenosis by angiography.
Figure 3. Angiographic images of a complex, long lesion of the SFA (a) treated with deployment of three Igaki–Tamai reabsorbable stents (b). Successful revascularization, determined as no greater than 30% final residual stenosis measured at the narrowest point of the treated segment, was achieved as shown on final intraoperative angiography (c). Table 2. Restenosis Rates Determined by CFD Flow Normal
Stenosis (%)
Preoperative
Discharge
1 mo
6 mo
12 mo
18 mo
24 mo
36 mo
0–20
0
32 (91)
30 (86)
25 (71)
25 (71)
32 (91)
32 (91)
30 (86)
PSVR Z 1.33
20–30
0
2
5
3
2
1
1
2
PSVR Z 1.6 PSVR Z 2.1
30–40 40–50
0 0
1 0
0 0
3 4
0 0
2 0
2 0
3 0
PSVR Z 2.4
50–60
0
0
0
0
0
0
0
0
PSVR Z 2.9 PSVR Z 3.4
60–70 70–80
0 3
0 0
0 0
0 0
0 0
0 0
0 0
0 0
PSVR Z 4.0
80–90
5
0
0
0
6
0
0
0
PSVR Z 7.0 No Flow
4 90 Occlusion
7 20
0 0
0 0
0 0
1 1
0 0
0 0
0 0
Values in parentheses are percentages. Test for trend (proportion of cases with normal flow) from discharge to 36 mo: χ2 ¼ 0.191, P ¼ .662. CFD ¼ color-flow duplex, PSVR ¼ peak systolic velocity ratio.
378
’
Endovascular Treatment of SFA Disease with Biodegradable Stents
Stent diameter was calculated as the maximum transverse diameter, defined as the maximum average distance between two opposite points of the hyperechogenic stent scaffold. Vessel diameter was intended from adventitia to adventitia. The measures of the vessel lumen were based on color-flow filling of the vessel lumen detected at CFD (Table 3). The maximum distance of the wall of the treated arterial vessel was recorded in early and midterm followup when the traceability of the stent was much more difficult later during follow-up as a result of progressive reduction of the hyperechogenic structure of the reabsorbing stent (18). Primary patency was defined as the absence of restenosis (Z 50% or PSVR o 2.4) in the target lesion. Primary assisted patency included patients with successful target vessel revascularization, and secondary patency included patients with successful target lesion revascularization. Follow-up included physical assessment, ABI measurements, and CFD at discharge, at 1, 3, and 6 months, and biannually thereafter. Follow-up was categorized according to time intervals: early (r 30 d), midterm (4 30 d but r 6 mo), and late (4 6 mo) follow-up.
Statistical Analysis Patient characteristics are reported as means ⫾ standard deviation for continuous data and as counts and percentages for categoric data. A paired t test and χ2 test for trend proportions were performed to assess the presence of remarkable differences in parameters between preand postoperative stages and during follow-up.
Silingardi et al
JVIR
removal of atheroma and thrombus with preliminary mechanical debulking (Rotarex Mechanical Thrombectomy System; Straub Medical, Wangs, Switzerland), and subsequent PTA with a drug-eluting balloon (Admiral 7 80 mm; Invatec, Frauenfeld, Switzerland; Fig 4). Seven symptomatic in-stent restenoses were successfully treated with PTA (Fig 5). Drug-eluting balloons (Admiral; Invatec) were used in four patients and nitinol stents were used in three patients, two of whom were treated for external iliac stenosis detected at late followup. No further repeat interventions were required throughout the remaining of the follow-up period (Table 4). Primary and secondary patency rates were 77.1% and 97.1%, respectively, at 24 and 36 months. Target lesion revascularization and target vessel revascularization rates were 22.8% and 5.5% at 24 and 36 months, respectively (Table 5). There were no cases of stent recoil or stent fracture during follow-up. A significant increase in hyperechogenicity of the scaffolded segment following stent implantation was noted in all treated lesions at CFD examinations during follow-up. The vessel wall presented hyperechogenic spots corresponding to the stent structure during early and midterm follow-up. A significant reduction in hyperechogenicity was detected in all patients from 12 months. Stent struts were visible on grayscale ultrasound scans in all patients (100%) at 6 months and in 94.3% at 12 months. Stent structure was partially visible in 10
Table 4. Results of SFA Endovascular Treatment with Bioresorbable Stent
RESULTS
Variable
Procedural success was confirmed at intraoperative angiography in 100% of cases. The average procedure time was 45 minutes (range, 20–75 min). No significant perioperative complications were noted (Table 4). All patients completed the scheduled follow-up protocol. The mean clinical follow-up period was 38.3 months (range, 30–58 mo). Asymptomatic restenosis was recorded in 10 patients (28.5%) within 30 days. The patients were not treated and were counseled to adhere strictly to the follow-up schedule. One in-stent occlusion at 12 months was recorded, which was successfully treated with the partial
’
Value
Procedural success
35 (100)
30-d complications
0
Follow-up (mo) Mean
38.3
Range
30–58
Symptomatic intrastent restenosis Time to symptomatic intrastent restenosis (mo) Mean
7 (20) 6.5
Range Intrastent occlusion
5–9 1 (2.8)
Values in parentheses are percentages. SFA ¼ superficial femoral artery.
Table 3. Results of CFD Preoperative and Postoperative Study Preoperative
Postoperative
1 d after Procedure
6 mo
12 mo
24 mo
36 mo
Measurement
(N ¼ 35)
(N ¼ 35)
(N ¼ 35)
(N ¼ 35)
(N ¼ 35)
(N ¼ 35)
(n ¼ 32)
Vessel diameter (mm)
5.2 ⫾ 1.3
5.6 ⫾ 1.3
5.6 ⫾ 1.3
5.6 ⫾ 1.3
5.6 ⫾ 1.3
5.6 ⫾ 1.3
5.6 ⫾ 1.2
Stent diameter (mm) Lumen (mm)
– 1.1 ⫾ 1.1
5.8 ⫾ 0.6 5.4 ⫾ 1.2
5.8 ⫾ 0.6 5.4 ⫾ 1.3
5.9 ⫾ 0.7 5.4 ⫾ 1.2
5.8 ⫾ 0.7 4.3 ⫾ 2.2.
ND 5.4 ⫾ 1.1
ND 5.4 ⫾ 1.0
Values presented as means ⫾ standard deviation. Paired t test, pre- vs postoperative: vessel diameter, P ¼ .207; lumen, P o .001. CFD ¼ color-flow duplex, ND ¼ not detected.
Volume 26
’
Number 3
’
March
’
2015
379
Figure 4. In-stent occlusion was observed at 12 months in the SFA (a) and treated with a partial removal of the in-stent atheroma and thrombus with a debulking technique and drug-eluting balloon angioplasty. Patency of the distal third of the SFA was shown on final intraoperative angiography (b).
patients at 24 months. Stent profile was no longer visible in all 35 cases at 30 months, suggesting complete stent structure reabsorption (Table 3).
DISCUSSION Although some data support the superiority of nitinol stent implantation over balloon angioplasty for atherosclerotic SFA lesions, rates of restenosis, stent thrombosis, and stent fracture remain high (19). DESs were designed in response to these suboptimal results, but DES treatment has been associated with subacute and late stent thrombosis (20). Results from early experiences with sirolimus-eluting stents in the treatment of SFA lesions have not yet proven to be superior to nitinol stents (4), and further studies are currently ongoing. Biodegradable stents represent a new frontier in the field of endovascular treatment for peripheral atherosclerotic lesions (9,10) through temporary vessel wall support and reduced mechanical stiffness over time, thereby reducing the risk of recoil and redefining restenosis rates (17,21,22). The pathophysiologic mechanisms of restenosis are minimized through the degradation of device materials into chemical substances without stimulation of the cell wall
foreign body reactive metabolism. Preliminary results from a dedicated study (unpublished data; ClinicalTrials.gov identifier NCT01403077) have not yet found any correlation between biodegradable stent implantation and any inflammatory cell infiltration or foreign body reaction. The optimal duration before complete absorption of a stent scaffold remains an open question. If this period is too short, the stent will lose radial force too early, threatening vessel patency and recoil. Alternatively, if the period is too long, all the advantages of temporary support are lost. Current indications suggest that optimal positive remodeling with vessel lumen enlargement is achieved following mechanical stent integrity for at least 6 months (23). Stent scaffolds in the present study were still visible at 6 months for all patients. Most biodegradable stent experience has been reported for coronary arterial disease; the first human trial for biodegradable stents (9) was conducted in 25 coronary artery stenotic lesions in 15 patients and showed a restenosis rate of 10.5% at 6 months. Nishio et al (24) confirmed the long-term safety of biodegradable stents 12 years later, reporting clinical outcomes at 10 years for the first 50 patients treated with biodegradable stents for coronary arterial disease. Despite the small sample size, biodegradable stent biocompatibility for human arteries
380
’
Endovascular Treatment of SFA Disease with Biodegradable Stents
Silingardi et al
’
JVIR
Figure 5. (a) Symptomatic in-stent restenosis (arrows) was detected on angiography and successfully treated with drug-eluting balloon angioplasty. Final intraoperative angiography confirmed successful treatment (b).
Table 5. Results of SFA Endovascular Treatment with Bioresorbable Stent Patency
Interval
Primary
Primary Assisted
Secondary
TLR
TVR
1y 2y
29 (82.8) 27 (77.1)
30 (85.7) 28 (80)
34 (97.1) 34 (97.1)
6 (17.1) 8 (22.8)
0 2 (5.71)
3y
27 (77.1)
28 (80)
34 (97.1)
8 (22.8)
2 (5.71)
.556
.535
.990
.557
.212
P value*
Values in parentheses are percentages. SFA ¼ superficial femoral artery, TLR ¼ target lesion revascularization, TVR ¼ target vessel revascularization. n Test for trend.
was confirmed; there were no signs of apparent inflammation or unexpected adverse events, and regular angiographic, intravascular, and clinical findings were highlighted throughout the follow-up. However, as previous experiences with DESs and drug-eluting balloons have shown, results obtained in coronary arteries are not always transferable to other vascular territories. Biamino et al (14) were the first to report endovascular treatment of the SFA with biodegradable stents in a
prospective, nonrandomized, two-center pilot study of 45 patients with TASC B and C lesions. The first phase reported a 6-month symptomatic restenosis rate of 25% (all successfully treated) and asymptomatic restenosis of 18%. No acute or subacute reocclusions were reported. In the second phase, an improved stent was implanted. In 65 patients, two reocclusions and a 28% rate of symptomatic restenosis were reported at 6 months (14). There are many studies currently ongoing that are analyzing the appropriateness of biodegradable stents for SFA. The ESPRIT I trial is currently evaluating the drugeluting bioresorbable vascular scaffold (Abbott Vascular) in 35 patients; this device was developed specifically for the SFA (TASC A lesions) and iliac arteries. A prospective, multicenter trial (unpublished data; ClinicalTrials.gov identifier NCT01403077) dedicated to symptomatic SFA atherosclerosis is currently assessing the efficacy of the Stanza bioresorbable scaffold (480 Biomedical, Watertown, Massachusetts). Standard endpoints are being investigated, along with the acute performance and subsequent stent strut encapsulation and reabsorption according to optical coherence tomography. The recently initiated SPRINT trial (unpublished data; ClinicalTrials.gov identifier NCT02097082) is assessing a drug-eluting version of
Volume 26
’
Number 3
’
March
’
2015
the Stanza scaffold (paclitaxel-eluting bioresorbable scaffold; 480 Biomedical) for de novo SFA lesions. Both trials are still under way, and no official data are available yet. To our knowledge, the present study reports the first midterm results with a PLLA biodegradable stent in SFA atherosclerotic disease, with encouraging results. However, the study has several limitations. This was an observational, single-center, nonrandomized study without a predetermined follow-up period. Late angiography was performed based on clinical indications only, so angiographic patency information was not available for asymptomatic patients. Because of the small patient cohort, statistical significance is difficult to achieve, and, as the significance level was not adjusted for multiple tests, the rates of type I error may be high. Patient selection bias is also inherent, as this study includes patients who were considered for endovascular treatment only. In addition, patient selection for stent placement was made at the discretion of the surgeon directly in the angiographic suite based on angiography, anatomy, and general clinical conditions. This study was carried out in a single center of regional reference, with an established interventional technique, so the results obtained in this series may not be reproducible and may require confirmation from multicenter studies. The midterm results with the use of a biodegradable PLLA stent for atherosclerotic SFA lesions seem promising in terms of low restenosis rates without stent recoil and vessel remodeling and may provide an optimal solution for patients with symptomatic peripheral artery disease. This new technology could open new possibilities in the treatment of femoropopliteal lesions, including the application of different drugs on the stent struts. These results require validation in larger trials that include patients with more complex lesions.
ACKNOWLEDGMENTS The authors thank Dr. Luigi Marcheselli for his statistical data evaluation and Johanna Chester for her editorial and critical review assistance.
REFERENCES 1. Schillinger M, Sabeti S, Loewe C, et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med 2006; 354:1879–1888. 2. Dick P, Wallner H, Sabeti S, et al. Balloon angioplasty versus stenting with nitinol stents in intermediate length superficial femoral artery lesions. Catheter Cardiovasc Interv 2009; 74:1090–1095.
381
3. Lammer J, Bosiers M, Zeller T. First clinical trial of nitinol self-expanding everolimus-eluting stent implantation for peripheral arterial occlusive disease. J Vasc Surg. 2011 Aug; 54(2):394–401. 4. Duda SH, Bosiers M, Lammer J, et al. Drug-eluting and bare nitinol stents for the treatment of atherosclerotic lesions in the superficial femoral artery: long-term results from the SIROCCO trial. J Endovasc Ther. 2006 Dec; 13(6):701–710. 5. Migliavacca F, Petrini L, Massarotti P, et al. Stainless and shape memory alloy coronary stents: a computational study on the interaction with the vascular wall. Biomech Model Mechanobiol. 2004; 2:205–217. 6. Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg 2000; 31:S1–S296. 7. Norgren L, Hiatt WR, Dormandy JA, et al. TASC II Working Group. InterSociety Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007; 43:S1–67. 8. Peuster M, Wohlsein P, Brügmann M, et al. A novel approach to temporary stenting: degradable cardiovascular stents produced from corrodible metal-results 6–18 months after implantation into New Zealand white rabbits. Heart 2001; 86:563–569. 9. Tamai H, Igaki K, Kyo E, et al. Initial and 6-month results of biodegradable poly-L-lactic acid coronary stents in humans. Circulation 2000; 102: 399–404. 10. Tsuji T, Tamai H, Igaki, et al. Biodegradable polymeric stents. Curr Interv Cardiol Rep 2001; 3:10–17. 11. Heublein B, Rohde R, Kaese V, Niemeyer M, Hartung W, Haverich A. Biocorrosion of magnesium alloys: a new principle in cardiovascular implant technology? Heart 2003; 89:651–656. 12. Ormiston JA, Serruys PW, Regar E, et al. A bioabsorbable everolimuseluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial. Lancet 2008; 371: 899–907. 13. Serruys PW, Ormiston JA, Onuma Y, et al. A bioabsorbable everolimuseluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods. Lancet 2009; 373:897–910. 14. Biamino G, Schmidt A, Scheinert D. Treatment of SFA lesions with PLLA biodegradable stents: results of the PERSEUS study. J Endovasc Ther. 2005; 12(Suppl I):5. 15. Vermassen F, Bouckenooghe I, Moreels N, Goverde P, Schroe H. Role of bioresorbable stents in the superficial femoral artery. J Cardiovasc Surg (Torino) 2013 Apr; 54(2):225–234. 16. Rutherford RB, Baker JD, Ernst C, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997; 26:517–538. 17. Moravej M, Mantovani D. Biodegradable metals for cardiovascular stent application: interests and new opportunities. Int J Mol Sci. 2011; 12(7): 4250–4270. 18. Sacks D, Marinelli DL, Martin LG, Spies JB. Reporting standards or clinical evaluation of new peripheral arterial revascularization devices. J Vasc Interv Radiol 2003; 14:395–404. 19. Mewissen MW. Self-expanding nitinol stents in the femoropopliteal segment: technique and mid-term results. Tech Vasc Interv Radiol 2004; 7:2–5. 20. Kuchulakanti PK, Chu WW, Torguson R, et al. Correlates and long-term outcomes of angiographically proven stent thrombosis with sirolimusand paclitaxel-eluting stents. Circulation 2006 Feb 28; 113(8):1108–1113. 21. Tsuji T, Tamai H, Igaki K, et al. Biodegradable stents as a platform to drug loading. Int J Cardiovasc Intervent 2003; 5:13–16. 22. Peeters P, Bosiers M, Verbist J, Deloose K, Heublein B. Preliminary results after application of absorbable metal stents in patients with critical limb ischemia. J Endovasc Ther. 2005 Feb; 12(1):1–5. 23. Onuma Y, Serruys PW. Bioresorbable scaffold: the advent of a new era in percutaneous coronary and peripheral revascularization? Circulation 2011 Feb 22; 123(7):779–797. 24. Nishio S, Kosuga K, Igaki K, et al. Long-term (410 years) clinical outcomes of first-in-human biodegradable poly-L-lactic acid coronary stents: Igaki-Tamai stents. Circulation 2012; 125:2343–2352.
381.e1
’
Endovascular Treatment of SFA Disease with Biodegradable Stents
Table E1 . Lesion Characteristics Characteristic No. of limbs
Value 35
Target artery Superficial femoral artery Surgical approach Anterograde TASC II classification A B Lesion length (mm) Mean
35 (100) 35 (100) 22 (62.8) 13 (37.2) 6.8
Range
2.5–13
Stenosis Occlusion
15 (42.9) 20 (57.1)
Mean stenosis length (cm) Mean Range
7.1 3–13
Mean occlusion length (cm) Mean Range
6.2 2.5–11
Reference vessel diameter (mm)
5.2 ⫾ 1.3
Below-knee runoff 2 vessels
11 (31.4)
3 vessels Preprocedure ABI Postprocedural ABI Number of stents
24 (68.6) 0.53 ⫾ 0.15 0.85 ⫾ 0.15 43
Stent length 36 mm
22 (62.8)
78 mm
21 (37.2)
Stent diameter 5 mm
6 (17.1)
6 mm
14 (40)
7 mm 8 mm
14 (40) 1 (2.9)
Values in parentheses are percentages. Values presented as means ⫾ standard deviation where appropriate. ABI ¼ ankle brachial index, TASC ¼ TransAtlantic Inter-Society Consensus.
Silingardi et al
’
JVIR
