Primary Stenting of TASC C and D Femoropopliteal Lesions: Results of the STELLA Register at 30 Months

Clinical Research Primary Stenting of TASC C and D Femoropopliteal Lesions: Results of the STELLA Register at 30 Months Jean-Michel Davaine,1,2 Julien Qu
erat,1 B
eatrice Guyomarch,3 Alain Costargent,1 Philippe Chaillou,1 Philippe Patra,1,4 and Yann Gou€effic,1,2,4 Nantes, France

Background: The 1-year results of the prospective register STELLA suggested that primary stenting of long femoropopliteal (FP) lesions (
15-cm) was a sure and effective treatment. However, the long-term results of this technique remain unknown. Methods: STELLA is a prospective monocentric register of patients treated for FP lesions
15cm (Trans-Atlantic Inter-Society Consensus [TASC] C and D) by direct stenting (FlexstarÒ, Bard). The patients with de novo atheromatous lesions were included between November 2008 and October 2009 when the guidewire had crossed the lesion. Restenoses were excluded. The follow-up was coordinated by a clinical research assistant. Clinical and ultrasound evaluation were carried out every 3 months for 12 months, then every 6 months up to 30 months. Restenosis was defined by an index of peak systolic velocity >2.4. Results: Among the 58 patients (62 limbs) included, 40.3% presented an effort ischemia and 59.7% a critical ischemia (CI). The mean age was 71 ± 12 years. The lesions were classified as TASC D in 37.1% of the cases. The median length of the stenting was 26 ± 18 cm. The average follow-up was 26.1 months (1e30). At 30 months, a complete follow-up was obtained in 55 patients (58 limbs). The rate of survival was 79.6%. Nine of the 11 patients deceased presented initially with CI. Death was in connection with CI in 2 cases. At the date of latest news, 98.3% of the patients were under antiaggregating treatment, 20% received antivitamin K treatment, 75% received statins, and 75% received angiotensin-converting-enzyme inhibitors. The rates of maintenance of the primary and secondary clinical improvement were 68.6 ± 6.0% and 82.6 ± 5.1% at 12 months and 65.1 ± 6.2% and 78.4 ± 5.6% at 30 months, respectively. The mean Rutherford index was 4.1 ± 1.0 in preoperative, 0.7 ± 1.2 at 12 months, and 0.6 ± 1.1 at 30 months (P < 0.001). Two major amputations were carried out at 9 and 28 months for patients initially with CI. The mean systolic pressure index was 0.6 ± 0.1 in preoperative and 1.0 ± 0.2 at 1-year and 0.9 ± 0.3 at 30 months (P < 0.001). The rates of primary and secondary patency were 66 ± 6.3% and 80.9 ± 9.5% at 12 months and 62.2 ± 6.6% and 77.2 ± 5.9% at 30 months, respectively. Between 0 and 12 months, 12 (19.3%) intrastent restenosis (ISR) were noted. One ISR was observed after 12 months. At the same period, we observed 11 and 1 target lesion revascularization, respectively. Conclusions: In the long run, the primary stenting of long FP lesions (
15-cm) is a safe and durable treatment. A strong clinical and ultrasound monitoring is indicated during the first year to maintain the clinical improvement.

Conflicts of interest: Y.G. is a consultant for Medtronic, Cook, and Cordis, and no conflict of interest is to be declared for the other authors. 1 CHU de Nantes, l’Institut du thorax, Service de Chirurgie Vasculaire, Nantes, France. 2

Laboratoire de Physiopathologie de la Resorption Osseuse, Inserm UMR 957, Nantes, France. 3 CHU de Nantes, l’Institut du thorax, Centre d’Investigation Clinique, Nantes, France. 4

Correspondence to: Yann Gou€effic, MD, PhD, Service de Chirurgie Vasculaire, CHU de Nantes, l’Institut du thorax, Nantes, F-44000 France; E-mail: [email protected] Ann Vasc Surg 2014; -: 1–11 http://dx.doi.org/10.1016/j.avsg.2014.03.033 Ó 2014 Elsevier Inc. All rights reserved. Manuscript received: December 16, 2013; manuscript accepted: March 15, 2014; published online: ---.

Universit
e de Nantes, Facult
e de M
edecine, Nantes, France.

1

2 Davaine et al.

INTRODUCTION During the last 10 years, the place of the endovascular treatment in the management of the femoropopliteal (FP) atheromatous lesions evolved considerably.1e3 The Trans-Atlantic Inter-Society Consensus (TASC) classification reflects these modifications on 2 levels. First of all, since 2007, one observed a widening of the indications of the endovascular treatment for TASC A, B, and C femoropopliteal lesions, whereas the first 2000 TASC recommendations limited the endovascular treatment to TASC A or B lesions.4,5 In addition, the severity of the lesions increased for the same grade. For example, in 2000, a TASC A femoropopliteal lesion was defined as stenosis <3-cm. Since 2007, TASC A lesions are defined as 10-cm stenoses or occlusions. The modification of the TASC classification was possible thanks to many studies that showed interest of stent compared with balloon angioplasty for TASC A and B lesions.6e8 The role of the endovascular treatment for longer lesions (>15-cm or TASC C and D) remains to be defined. Various therapeutic strategies can be planned to treat long FP lesions, such as auto-expandable stent, drug eluting balloon or stent, or covered stent. Currently, there exist 2 specific registers of long FP lesions.9,10 In these 2 registers, the patients were treated by direct stenting. In 2011, Dake et al.11 reported the results at 1 year of the register studying the active paclitaxel eluting stent Zilver PTXÒ. In this register, among the 787 patients included, 354 TASC C and D lesions (39.3%) were treated. If the 1-year results of these 3 registers were promising, the long-term evolution is dubious. In this work, we report for the first time the longterm results of a prospective register of the stenting of long FP lesions.

METHODS STELLA is a monocentric prospective register of patients presenting de novo FP atheromatous lesions classified as TASC C and D (>15 cm). The patients were included between November 2008 and October 2009. Endovascular treatment was proposed as first intention. The criteria of inclusion and exclusion are shown in Table I. Procedures The patients were treated under local anesthesia associated with sedation. A general anesthesia was indicated in the event of agitation of the patient. The access to the lesions was obtained by

Annals of Vascular Surgery

anterograde or retrograde femoral puncture and crossover. A 6F 11-cm or 45-cm long introducer (DestinationÒ, Terumo, St Quentin en Yvelines, France) was selected according to the type of approach. Once the introducer was positioned, a heparin bolus of 50 IU/Kg was injected by intravenous route. The stenoses were crossed endoluminally. In the event of occlusions a technique of subintimal recanalization was carried out. Briefly, a plane of dissection was created by a loop formed by a stiff hydrophilic guide (RadiofocusÒ, Guidewire stiff 0.035, 260 cm). The progression of the guide was done thanks to the use of a 0.035 carrier balloon catheter (OptaproÒ, Cordis, Issy, France). Distally, the reentry in the vessel lumen was confirmed by the injection of a small quantity of product of contrast through the lumen of the balloon catheter. No device of reentry was used. Primary stenting was indicated of first intention. In the event of severe calcifications a predilatation using a 3-mm diameter balloon was carried out. Dimensions of stent were chosen thanks to the balloon catheter by visual estimation and to correspond to the diameter of the target vessel and the length of the lesion plus 5e 10-mm upstream and downstream. The maximum length of the available stents was 170 mm. The overlapping between 2 stents was 10-mm. The stents used for this study were 6- or 7-mm diameter LifestentÒ (Bard Peripheral Vascular, Tempe, AZ). After implantation, the stents were remodeled with a balloon (Optapro) whose diameter was 1 mm less than the diameter of the implanted stent to ensure an optimal affixing and to reduce the traumatism inflicted to the media.12 The length of the remodeling balloon did not exceed that of stent. A peroperative arteriography controlled the immediate result. The associated arterial lesions justifying a treatment were dealt with in the same time. The significance of a lesion was determined by the symptomatology of the patient, analysis of the preoperative imagery (angio-magnetic resonance imaging, angiocomputed tomography, and ultrasound study) and by peroperative arteriographic observations. The closing of the point of puncture was obtained by manual compression during 15 min, and, in the case of ambulatory procedures, with a percutaneous arterial closure (AngiosealÒ, St-Jude Medical, France). During hospitalization, the patients received a daily subcutaneous preventive heparin dose. In postoperative, a treatment by 2 antiplatelet agents (APA; aspirin 75e160 mg/day and clopidogrel 75 mg/day) was prescribed for 6 months. After 6 months, a treatment by clopidogrel only was maintained.13 In the event of treatment by antivitamin K (AVK) with the long course, aspirin only

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Table I. Criteria of inclusion and exclusion of the study Criteria of inclusion

Criteria of exclusion

    

    

Age
50 years Symptomatic patients (Rutherford 3e6) Femoropopliteal atheromatous occlusive lesions >15 cm in length TASC II C and D lesions Upstream and downstream flow compatible with an FP revascularization or associated lesions treated in the same time (1 patent leg artery requested)  Crossing of the lesions using a guide  Written and signed consent obtained from the patient  Patients indexed in the files of the social security

     

was used. The observance of the medical care was checked with each stage of the follow-up. Follow-up The patients were followed up in consultation. The major cardiovascular events (MCE) were registered in a systematic way. The follow-up included a medical examination, the measurement of the ankle brachial index, and an ultrasound examination at 1, 3, 6, 9, and 12 months then every 6 months up to 30 months. Information was collected in a prospective way in a standardized database. The exhaustive character of the information obtained during the consultations was systematically checked by the surgeon in charge of the study and, in the event of missing data, the software of the hospital was consulted and if needed the referent physician of the patient was called. Fractures of stents were sought at 1-year by plain radiographies with 2 incidences separated by at least 45 . To be objective, the analysis of stents fractures was entrusted to an independent laboratory (CoreLab, BadKrozingen, Germany). The classification by Jaff et al.14 was used as reference to analyze the fractures. Two clinical research assistants were in charge of the follow-up of the study. Criteria of Judgment The primary criterion was the primary clinical improvement at 12 months. The secondary criteria included the secondary clinical improvements, the primary and secondary patencies, technical success, major and minor complications, MCE, the rate of limb salvage, and the rates of target lesion revascularisation (TLR), target extremity revascularisation

Restenosis Nonatheromatous disease Asymptomatic lesion Acute ischemia or acute thrombosis Aneurysm or lesion adjacent to an aneurysm Patient enrolled in another trial Patient refusal Pregnancy Known allergy to heparin, aspirin, or another antithrombotic agent Absence of written consent Life expectancy <1 year

(TER), intrastent restenosis (ISR), thromboses, and fractures of stents.15 Definitions Primary clinical improvement was defined by the maintenance of the clinical improvement of at least 1 category according to the Rutherford classification for the claudicants and by the disappearance of rest pain and the healing of the trophic disorders in the patients presenting with CI, without a new reintervention on the target lesion, in the surviving patients. Secondary clinical improvement was defined as the primary clinical improvement, but with the inclusion of the cases with a reintervention on the target lesion. Primary patency was defined by the persistent patency of the treated arterial segment without a new endovascular or surgical revascularization. Technical success was defined by obtaining a residual diameter >30% checked by the peroperative arteriography. The minor complications were those occurring in the perioperative period that did not require an additional therapeutic gesture or a prolongation of the hospitalization. The major complications were those occurring in the perioperative period that required reoperation or a prolongation of the hospital stay of at least 24 hr. The MCE included the deaths, major amputations, and severe complications in relation with the procedure or a defect of the material used. The TLR represented the endovascular or surgical reinterventions at the level of the target lesion (and 1-cm upstream and downstream to take into account the phenomena occurring at the edge of the stent) in the patients surviving without amputation. TERs were the procedures necessary to treat a lesion located in the same limb but apart from the zone initially treated. ISR was defined by a reduction of 50% of the

4 Davaine et al.

diameter of the lumen and by an index of peak systolic velocity >2.4. The fractures were searched on plain radiographies carried out at 12 months. Statistical Analyzes The statistical results were calculated in intention to treat from prospective data. The continuous variables were presented in the form of mean and standard deviation. The categorical variables were presented as percentages. The demographic data and the comorbidities of the patients were related to the number of patients, whereas the patency data were calculated according to the number of limbs. The rates of TLR and TER were represented as survival curves according to the method of KaplaneMeier. For the patients deceased or lost to follow-up before the end of the follow-up, the last information available were taken into account. A value of the P < 0.05 was regarded as significant. The data were analyzed using the dedicated software of statistical analysisdStatistical Package for the Social Sciences (SPSS; SPSS Inc., Chicago, IL).

RESULTS Characteristics of the Population A total of 58 patients (62 limbs) were included over a period of 1 year. In the same time, 302 patients presenting FP lesions were treated in our center (231 endovascular and 71 surgical revascularizations). The mean age of the patients was 71.4 ± 12 years and most of them were men (n ¼ 42, 72.4%). In 40.3% of the cases (25 limbs), the indication was an effort ischemia after failure of medical care and in 59.7% of the cases (37 limbs), the indication was a critical ischemia (CI; Table II). Perioperative Data Among the treated limbs, 62.9% (n ¼ 39) presented TASC C lesions and 37.1% (n ¼ 23) presented TASC D lesions. (Table III) All the treated lesions presented zones of occlusion. In most of the cases (38 limbs, 61.3%), an access by retrograde femoral puncture and crossover was carried out. The median length of stenting was 260 ± 180 mm with a mean of 2.2 ± 0.91e4 stents by procedure. In the 62 procedures carried out, 48 popliteal arteries were concerned with the implantation of stents (77.4%). An associated procedure was carried out in 20 limbs (32.2%) by endovascular route, and in 4 other limbs (6.4%) by open surgery (Table III). One perioperative death was due to cardiac decompensation. Six major complications (9.7%) were noted, 2

Annals of Vascular Surgery

Table II. Characteristics of the population Data

Age (years) Men Tobacco Active Previous Hypertension Dyslipidemia Diabetes Type I Type II Renal insufficiency Dialysis Obesity (BMI > 25) Coronary lesions Cerebrovascular disease Rutherford classification stage 3 4 5 6 Clinical presentation Claudication Chronic critical ischemia

71.4 ± 12 42 (72.4) 34 (58.6) 13 (22.4) 21 (36.2) 48 (82.8) 29 (50) 25 (43.1) 2 (3.4) 23 (39.7) 13 (22.4) 1 (1.7) 27 (46.6) 28 (48.3) 9 (15.5) 25 13 20 4

(40.3) (21) (32.2) (6.5)

25 (40.3) 37 (59.7)

BMI, body mass index. Data are expressed as either mean ± standard deviation or n (%).

hematomas at the point of puncture requiring a prolonged hospitalization, 1 syndrome of reperfusion of the treated limb, 1 acute coronary syndrome, 1 cardiac decompensation, and 1 digestive functional occlusive syndrome. The analysis by subgroups according to the clinical status (effort ischemia and CI) and according to the lesions (TASC C and D), found a prevalence of CI among older patients (P ¼ 0.004) and women (P ¼ 0.04). In addition, the number of stents implanted, the lengths of lesions, and stenting were significantly higher for TASC D than TASC C lesions (P ¼ 0.0001). Follow-up The mean duration of follow-up was 26.7 ± 7.8 months1e30. (Table IV) At 30 months, only 3 patients (3 members) did not have a complete follow-up (5.2%). During the follow-up, we observed 11 deaths, with a rate of survival of 80.6 ± 5.3%. Nine of these 11 patients initially presented with CI and in 2 cases the death was directly related to the CI. Two major amputations were carried out at 9 and 28 months in patients with an initial CI. The rates of maintenance of the primary clinical improvement were 68.6 ± 6.0% and 65.1 ± 6.2% at

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Primary stenting of TASC C and D FP lesions 5

Table III. Intraoperative and immediate postoperative data

Table IV. Follow-up of the patients Data

TASC II lesions C D Access Crossover Anterograde puncture Length of the lesions (mm, IQR) Length of the segment treated (mm, IQR) Number of stents per patient (N ) Number of stent implanted 1 2 3 4 Diameter of stents 6-mm 7-mm Number of leg arteries (by ultrasound) 1 2 3 Not available Associated procedures Endovascular Aortic bifurcation Common iliac artery External iliac artery Internal iliac artery Common femoral artery Tibial arteries Contralateral iliac artery Open surgery Femoral endarterectomies Contralateral femoropopliteal bypass Minor amputations Major amputations Major cardiovascular events Ambulatory procedures Duration of fluoroscopy (min) Irradiation (mGy.m2) Duration of procedure (min) Contrast product (mL) Duration of stay (days) Perioperative complications Minor Major

39 (62.9) 23 (37.1) 38 (61.3) 24 (38.7) 220 ± 160 260 ± 180 2.2 ± 0.9 134 (100) 16 (25.8) 22 (35.5) 22 (35.5) 2 (3.2) 134 (100) 104 (77.6) 30 (22.4) 12 18 14 18

(19.4) (29) (22.6) (29)

20 (32.2) 1 (1.6) 1 (1.6) 6 (9.7) 2 (3.2) 2 (3.2) 7 (11.3) 1 (1.6) 4 (6.4) 3 (4.8) 1 (1.6) 3 (4.8) 0 (0) 2 (3.4) 5 (8.1) 18.9 ± 10 3.3 ± 3 79 ± 36 87 ± 36 3±4 5 (8.1) 6 (9.7)

IQR, interquartile range. Data are expressed as either mean ± standard deviation or n (%).

12 and 30 months, respectively. The rates of maintenance of the secondary clinical improvement at the same period of time were 82.6 ± 5.1% and 78.4 ± 5.6%, respectively (Fig. 1). Among the surviving patients, only 1 limb, which was considered

Event

Data

Death Cardiac decompensation (day 2) CVA (3rd month) Hemopathy (3rd month) Neoplasia (6th and 20th month) Critical Ischemia- related (14th and 29th month) Unknown (12th, 24th and 29th month) Major cardiovascular events APE (3rd month) Aortocoronary bypass (6th month) Acute coronary syndrome (6th month) Pacemaker (6th month) Amputations Minor Major (9th and 28th month) Patients with trophic disorders Inclusion (62 limbs) 12th month (54 limbs) 30th month (45 limbs) Infection GI bleeding Intrastent restenosis 1st month 3rd month 6th month 9th month 12th month 30th month Stent thromboses 1st month 3rd month 6th month 9th month 12th month 30th month

10 1 1 1 2 2

(17.1) (1.7) (1.7) (1.7) (3.4) (3.4)

3 4 1 1 1 1 2 0 2

(5.2) (6.8) (1.7) (1.7) (1.7) (1.7) (3.4) (0) (3.4)

24 2 1 2 1 13 0 3 5 2 2 1 7 1 0 3 1 2 1

(38.7) (3.7) (2.2) (3.2) (1.7) (20.9) (0) (4.8) (8.1) (3.2) (3.2) (1.6) (11.3) (1.6) (0) (4.9) (1.6) (3.2) (1.6)

APE, acute pulmonary edema; CVA, cerebrovascular accident; GI, gastrointestinal. Data are expressed as n (%).

as improved at 1-year, was not in this status at 30 months. The clinical evolution according to the Rutherford classification found a clear clinical improvement as of the first month that was confirmed until the 30th month (Fig. 2). The mean index of Rutherford was 4.0 ± 1.0 at the time of inclusion, 0.7 ± 1.2 at 12 months and 0.6 ± 1.1 at 30 months (P < 0.001). In parallel, the mean index of systolic pressure was of 0.6 ± 0.1 at the time of inclusion, 1.0 ± 0.2 at 12 months, and 0.95 ± 0.3 at 30 months (P < 0.001). In terms of healing, 24 of the 62 limbs (38.7%) presented trophic disorders. At 12 months, 2 of the 54 limbs (3.7%) presented trophic disorders. At 30 months, 1 limb of 45 (2.2%) presented trophic disorders.

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Fig. 1. Representation according a survival curve of the primary clinical improvement (Primary cl. imp.) and secondary (Secondary cl. imp.).

Fig. 2. Clinical evolution of the patients according to the classification of Rutherford. When enrolled, 59.8% of the patients presented a CI (R 4e6). At 30 months, 93.2% of the patients were asymptomatic or presented a broad claudication (R 0e2), 4.5% of the patients had a tight claudication (R 3) and 2.3% presented a CI (R 4e6). R, Rutherford classification.

The primary patency rates were 66 ± 6.3% at 12 months and 62.2 ± 6.6% at 30 months. The secondary patency rates were 80.9 ± 9.5% and 77.2 ± 5.9% at 12 months and 30 months, respectively (Fig. 3). At the end of the follow-up period we observed 13 ISR of which 12 had occurred during the first year. Eight intrastent thromboses occurred, including 7 during the first year (Table IV). The rates of indemnity of TLR and TER at 12 months were 80.3 ± 5.3% and 96.5 ± 2.4%,

respectively, and remained unchanged at 30 months (Fig. 4). At the end of the follow-up period, 98.3% of the patients received APA, 20% received AVK, 75% received statins, and 75% received angiotensinconverting-enzyme (ACE) inhibitors. The maintenance of the primary and secondary clinical improvement and the primary and secondary patencies were analyzed by comparing different subgroups of patients, patients presenting with TASC C versus TASC D lesions and patient presenting an effort ischemia versus patients presenting with CI (Table V). The rates of maintenance of the primary clinical improvement at 30 months were 75.9 ± 7% for TASC C patients and 47.0 ± 10.6% for TASC D patients (P ¼ 0.02). The difference between the rates of primary patency of TASC C and D lesions at 30 months approached near significance (71.3 ± 7.7% and 49.0 ± 10.8%; P ¼ 0.06). Among the other analyzes, differences did not reach significance (Table V). The comparison of subgroups (TASC C/TASC D and effort ischemia/CI) also studied the following variables: mean score of Rutherford, SPI, intrastent restenoses, thromboses of stents, TLR, and TER. TASC C lesions presented a significantly lower mean Rutherford score and a significantly higher SPI in comparison with group TASC D. TASC D lesions developed significantly more ISR than TASC C lesions (Table V). Univariate and multivariate analyses did not find any factor such as diabetes, female gender, downstream arteries, or diameter of stent as influencing significantly the occurrence of ISR at 12 or 30 months.

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Primary stenting of TASC C and D FP lesions 7

Fig. 3. Representation according to a survival curve of the primary and secondary patency.

Regarding the fractures of stents, this study did not lay down a radiographic evaluation at 30 months.

DISCUSSION Endovascular treatment of TASC A and B femoropopliteal lesions has now become the treatment of first intention for most of the surgeons. The rates of technical success are now quite high.16,17 Currently there exist few data concerning the results obtained after endovascular treatment of the longest lesions, that is TASC C and D (>15 cm).9,10,18 Moreover the durability of the endovascular treatment remains prone to controversies taking into account the risk of ISR and of fractures of stent. The results of this study are in favor of the long-term persistence of the clinical improvement obtained after 1 year of follow-up. Indeed, the rates of maintenance of the primary and secondary clinical improvement obtained at 12 months (69% and 83%) were close to those obtained at 30 months (64.6% and 76.3%). The same observation was valid for the primary patency (66% and 80.9% at 12 months and 60% and 74% at 30 months). It is interesting to observe that the incidences of ISR and thromboses decrease after 12 months. After 12 months we observed only 1 thrombosis and ISR. Considering these results, one should keep in mind that around 60% of the patients presented with IC at the time of inclusion. In the literature, few studies reported the results of FP stenting in the midterm or long term.

Concerning TASC C and D lesions, the follow-up was limited to 1 year.9,18e20 For TASC A and B lesions, the ABSOLUTE study showed a 45.7% rate of ISR at 24 months after primary stenting. The authors concluded to a maintained clinical and morphologic benefit compared with angioplasty with optional stenting.21 The RESILIENT (Randomized study comparing the Edwards Self-expanding Lifestent vs. angioplasty-alone In Lesions INvolving The SFA and/or proximal popliteal artery) study presented a follow-up going up to 3 years and reported a rate of indemnity of TLR reaching 75.5% at 3 years.22 In the RESILIENT study all the lesions were <15-cm long and the patients were claudicants.22 More recently, Kralj et al.23 reported a series of 45 patients treated by primary stenting with a primary patency rate of 74.3% at 3 years. However, the mean length of the treated lesions was 53-mm for stenoses and 74-mm for occlusions. Recent meta-analyses sum these data by showing that most of the studies dealt with lesions <15-cm and included claudicants with a follow-up limited to 1 year.24 Other therapeutic methods can be planned to treat long FP lesions. In the VIASTAR (Viabahn endoprosthesis with PROPATEN bioactive surface (VIA) vs bare-nitinol stent in the treatment of long lesions in superficial femoral artery occlusive disease) study, the 1-year patency in the group receiving covered stents impregnated with heparin was significantly higher than in the group receiving naked nitinol stents (71.3% vs. 36.8%, P ¼ 0.001).25 However, although more restenoses were observed in the bare stent group, the rates of

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Fig. 4. Survival curves of the indemnity of (A) TLR and (B) TER in 30-month follow-up.

reinterventions on the target lesion were not significantly different between the 2 groups, without a precise explanation. Moreover, the authors reported more thromboses in the covered stents group with more severe consequences such as acute ischemia. The clinical improvement according to the Rutherford scale was the same at 1 year in the 2 groups, that is, 84% (vs. 83% at 1 year in our study). The treatment of the long lesions with active balloons is also a therapeutic option. However, the published studies only report results for lesions with a mean length <15-cm.26e28 The analysis of mortality must take into account the high rate of patients included with a CI (59.7%). The risk of death at 1 year for a patient with CI is estimated at 20% and the risk of major

amputation is 50%.4 The results obtained here are in short of these references. The quality of a prospective register is founded on the rigor of the follow-up of the patients. In our study, the mean duration of the follow-up was 26 ± 1 months and 5% of the patients were lost to follow-up (n ¼ 3). The prospective character of this study implied a medical and paramedical monitoring with a special attention to the observance of the medicinal treatment. The observance was relatively good because at the date of the last follow-up, 98% of the patients received APA and 75% were given statins and ACE inhibitors. Twelve of the 13 ISR and 7 of the 8 thromboses were diagnosed during the first year. These figures show the absence of recurrence of intrastents events after the 12th month following their implantation.

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Table V. Subgroup analysis (TASC C versus TASC D and claudicants versus CI) of the rate of I cl. imp. and II cl. imp., of the rates of PP and SP, and the rates of TLR, TER, ISR, and thromboses of stents at 30 months of follow-up Subgroup

TASC C

I Cl. imp. II Cl. imp. PP SP TLR (indemnity) TER (indemnity) ISR (indemnity) Thromboses (indemnity)

75.9 85.9 71.3 82.4 85.9 94.6 88.3 93.8

± ± ± ± ± ± ± ±

TASC D

7.0 5.9 7.7 6.6 5.9 3.7 5.6 4.3

47.0 63.9 49.0 68.7 72.2 100 69.8 95.5

± ± ± ± ±

10.6 11.4 10.8 10.8 9.7

± 10.5 ± 4.4

P value

Claudicants

CI

0.02 0.06 0.06 0.25 0.21 0.3 0.07 0.89

74.6 82.5 68.1 81.0 87.0 100 81.7 91.6

59.5 75.8 58.3 74.6 76.2 94.1 81.8 96.6

± ± ± ± ±

9.0 8.1 10.1 8.8 7.0

± 8.4 ± 5.7

P value

± ± ± ± ± ± ± ±

8.1 7.6 8.5 7.9 7.4 4.1 6.8 3.4

0.24 0.57 0.32 0.47 0.28 0.24 0.86 0.42

I Cl. imp., primary clinical improvement; II Cl. imp., secondary clinical improvement; PP, primary patency; SP, secondary patency.

The higher incidence of restenoses during the first postoperative year encourages undertaking a closer monitoring during the first year, in particular, to avoid the evolution toward intrastent thrombosis, which is more difficult to treat. The data of the literature confirm that most of the ISR occur in the first year after the treatment and that very few events occur beyond.21,29,30 The small number of events observed is in favor of a spacing of the follow-up after the first year. The rate of ISR was 21% at 30 months, which is relatively low taking into account the length of the lesions. The technique of recanalization could partly explain these results.31 When the guide passes in the subintimal plane, the media is divided into 2 on both sides of the subintimal plane.32 The quantities of smooth muscular cells would then be reduced all around the bars of stent, limiting the risk of ISR. One of the elements to be also considered in the interpretation of the low rate of ISR is the distinction between thromboses and ISR. In our study, the closer follow-up made it possible to distinguish ISR and thromboses, because the thromboses occur without any preliminary sign of restenosis.33 In STELLA and DURABILITY-200, the frequencies of the ultrasound monitoring were every 3 months and 6 months, respectively. The cumulated rates of thromboses and ISR at 12 months were 30.6% (11.3% for thromboses and 19.3% for ISR) in STELLA and 34% in DURABILITY-200 (24% for thromboses and 10% for ISR). Thus, it cannot be excluded that in DURABILITY-200, some thromboses were the consequence of the evolution of an ISR not diagnosed because of the spacing of the ultrasound follow-up. The subgroups analysis tended to show, in spite of the lack of significance related to the small number of patients, better results for the patients with effort ischemia and for TASC C lesions. The same observations were made recently by Yin et al.34 In the future the clinical presentation of the patients and the TASC

classification should be taken into account in the stratification of the clinical studies. The principal limits of this study are the absence of control groups and the relatively low number of patients included, limiting the interpretation of the results. Moreover, the evaluation of the results is focused on FP procedures whereas in w30% of the cases, an associated procedure was carried out at the suprainguinal or infrapopliteal levels. These procedures certainly have an impact on the clinical evolution of the patients concerned. Finally the radiographic evaluation at 12 months made it possible to highlight a high number of fractures (17.7% of fractures per limbs) whose clinical impact, evaluated elsewhere, remained modest.35 If one refers to other works,21,22,36 the incidence of new fractures of stents after 1 year is weak. Whichever this number, taking into account the results in terms of clinical improvement and of patency at 30 months, one can suppose that the clinical and hemodynamic impact of these possible fractures is limited.

CONCLUSIONS In the STELLA prospective register, the treatment by primary stenting of long FP lesions appears sure, effective, and durable in terms of clinical and morphologic results. The reinterventions were primarily necessary during the first year and made it possible to maintain the initial results. In the longterm, follow-up the reinterventions on the targets lesions are less frequent. These observations are in favor of a closer clinical and ultrasound follow-up during the first year.

We thank Mrs. Carine Montagne and Annie Guillard for their excellent monitoring and for the organization of the follow-up of this register.

10 Davaine et al.

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