Advertisement

Femoropopliteal In-stent Restenosis Repair: Midterm Outcomes After Paclitaxel Eluting Balloon Use (PLAISIR Trial)

Open ArchivePublished:November 24, 2016DOI:https://doi.org/10.1016/j.ejvs.2016.10.002

      Objective

      The aim was to assess 18 month outcomes of the paclitaxel eluting balloon (PEB) in patients with femoropopliteal (FP) in-stent restenosis (ISR).

      Methods

      In a national prospective and multicentre cohort study, symptomatic patients with femoropopliteal in-stent restenosis were included from January 2012 to June 2013. Patients were treated by paclitaxel eluting balloon angioplasty (In Pact Admiral, Medtronic, Santa Rosa, CA, USA). Clinical and duplex scan follow-up evaluations were performed at 1, 3, 6, 9, 12, and 18 months. The primary endpoint was freedom from target lesion revascularisation (TLR) at 12 months. Secondary endpoints were major adverse cardiovascular events (MACE), Target extremity revascularisation (TER), primary and secondary sustained clinical improvement, recurrent restenosis rate, primary and secondary patency, quality of life assessed by EQ-5D questionnaire, technical success, clinical success, and length of stay

      Results

      A total of 53 patients were enrolled. After a blinded review, 10 patients were defined as protocol violation because restenosis occurred more than 2 years after stent implantation. Procedures were performed in 55 limbs, 48 (87%) for claudication and 7 (13%) for critical limb ischaemia. The mean diameter and length of PEB were 6 ± 0.57 mm and 86 mm ± 32 mm, follow-up was 17 months (range 1–19). At 1 year, the survival rate was 96 ± 2.7% and freedom from TLR and TER were 90.2 ± 4.2% and 85 ± 5%, respectively. Sustained primary and secondary clinical improvements were 78.6 ± 5.7% and 92.0 ± 3.8%, respectively. At 1 year, the primary patency rate was 83.7 ± 5.0%. Prior to the procedure, the mean EQ-5D score was 66 ± 14 and 74 ± 16 at 1 year (p = .10). Two patients died during follow-up; one patient died 33 days after the procedure because of limb ischaemia.

      Conclusion

      PEB for the treatment of FP ISR is associated with a low rate of re-interventions and restenosis. Clinical improvement is maintained at 18 months.

      Keywords

      This study confirms the good results of the paclitaxel eluting balloon (PEB) in the treatment of femoropopliteal (FP) in-stent restenosis (ISR). It will help to define PEB angioplasty as the Gold Standard for the treatment of FP ISR.

      Introduction

      Over the last 20 years endovascular therapy has become the standard of care for revascularisation of the femoropopliteal (FP) arteries for Trans-Atlantic Inter-Society Consensus (TASC) A and B lesions, and could also be an option for TASC C and D lesions, although bypass is still the standard of care for the long FP lesion. However, the Achilles heel of this technique remains restenosis. Restenosis is a local process associated with elastic recoil, intimal hyperplasia, and constrictive remodelling. The overall vessel diameter reduction that occurs in constrictive remodelling is not well defined, but likely involved matrix turnover under the control of proteinases, particularly metalloproteinases. Intimal hyperplasia includes inflammatory phenomena, migration, and proliferation of smooth muscle cells (SMCs) and also extracellular matrix (ECM) deposition.
      • Hoffmann R.
      • Mintz G.S.
      • Dussaillant G.R.
      • Popma J.J.
      • Pichard A.D.
      • Satler L.F.
      • et al.
      Patterns and mechanisms of in-stent restenosis. A serial intravascular ultrasound study.
      Prevention of restenosis was first focused on elastic recoil and constrictive remodelling by developing stents. Therefore, in-stent restenosis (ISR) is primarily due to intimal hyperplasia. The failure of plain balloon angioplasty to treat ISR prompted the development of other therapies to treat ISR.
      • Tosaka A.
      • Soga Y.
      • Iida O.
      • Ishihara T.
      • Hirano K.
      • Suzuki K.
      • et al.
      Classification and clinical impact of restenosis after femoropopliteal stenting.
      However, most of them did not show promising results. Indeed directional atherectomy
      • Shammas N.W.
      • Shammas G.A.
      • Helou T.J.
      • Voelliger C.M.
      • Mrad L.
      • Jerin M.
      Safety and 1-year revascularization outcome of SilverHawk atherectomy in treating in-stent restenosis of femoropopliteal arteries: a retrospective review from a single center.
      • Trentmann J.
      • Charalambous N.
      • Djawanscher M.
      • Schäfer J.-P.
      • Jahnke T.
      Safety and efficacy of directional atherectomy for the treatment of in-stent restenosis of the femoropopliteal artery.
      • Zeller T.
      • Rastan A.
      • Sixt S.
      • Schwarzwälder U.
      • Schwarz T.
      • Frank U.
      • et al.
      Long-term results after directional atherectomy of femoro-popliteal lesions.
      shows a primary patency rate and freedom from target lesion revascularisation (TLR) at 1 year ranging from 25% to 54% and from 53% to 56%, respectively. Cutting balloon angioplasty failed to prove superiority when compared with conventional percutaneous transluminal angioplasty (PTA).
      • Dick P.
      • Sabeti S.
      • Mlekusch W.
      • Schlager O.
      • Amighi J.
      • Haumer M.
      • et al.
      Conventional balloon angioplasty versus peripheral cutting balloon angioplasty for treatment of femoropopliteal artery in-stent restenosis: initial experience.
      Indeed, the primary patency rate at 1 year was 35% and freedom from TLR was 59%. With laser atherectomy and PTA, the primary patency rate was 48%, and freedom from TLR rates ranged from 49% to 77%.
      • Zeller T.
      • Rastan A.
      • Sixt S.
      • Schwarzwälder U.
      • Schwarz T.
      • Frank U.
      • et al.
      Long-term results after directional atherectomy of femoro-popliteal lesions.
      Other devices have limitations with regards to ease of use, technical limitations, or cost such as brachytherapy,
      • Werner M.
      • Scheinert D.
      • Henn M.
      • Scheinert S.
      • Bräunlich S.
      • Bausback Y.
      • et al.
      Endovascular brachytherapy using liquid Beta-emitting rhenium-188 for the treatment of long-segment femoropopliteal in-stent stenosis.
      or laser atherectomy.
      • Shammas N.W.
      • Shammas G.A.
      • Hafez A.
      • Kelly R.
      • Reynolds E.
      • Shammas A.N.
      Safety and one-year revascularization outcome of excimer laser ablation therapy in treating in-stent restenosis of femoropopliteal arteries: a retrospective review from a single center.
      • Yeo K.-K.
      • Malik U.
      • Laird J.R.
      Outcomes following treatment of femoropopliteal in-stent restenosis: a single center experience.
      • Laird J.R.
      • Yeo K.K.
      • Rocha-Singh K.
      • Das T.
      • Joye J.
      • Dippel E.
      • et al.
      Excimer laser with adjunctive balloon angioplasty and heparin-coated self-expanding stent grafts for the treatment of femoropopliteal artery in-stent restenosis: twelve-month results from the SALVAGE study.
      • Dippel E.J.
      • Makam P.
      • Kovach R.
      • George J.C.
      • Patlola R.
      • Metzger D.C.
      • et al.
      Randomized controlled study of excimer laser atherectomy for treatment of femoropopliteal in-stent restenosis: initial results from the EXCITE ISR trial (EXCImer Laser Randomized Controlled Study for Treatment of FemoropopliTEal In-Stent Restenosis).
      A covered stent
      • Bosiers M.
      • Deloose K.
      • Callaert J.
      • Verbist J.
      • Hendriks J.
      • Lauwers P.
      • et al.
      Superiority of stent-grafts for in-stent restenosis in the superficial femoral artery: twelve-month results from a multicenter randomized trial.
      or paclitaxel eluting stent
      • Dake M.D.
      • Scheinert D.
      • Tepe G.
      • Tessarek J.
      • Fanelli F.
      • Bosiers M.
      • et al.
      Nitinol stents with polymer-free paclitaxel coating for lesions in the superficial femoral and popliteal arteries above the knee: twelve-month safety and effectiveness results from the Zilver PTX single-arm clinical study.
      showed promising results but stent superposition could result in the lumen loss.
      Recently, the paclitaxel eluting balloon (PEB) has shown promising results in preventing FP restenosis.
      • Rosenfield K.
      • Jaff M.R.
      • White C.J.
      • Rocha-Singh K.
      • Mena-Hurtado C.
      • Metzger D.C.
      • et al.
      Trial of a paclitaxel-coated balloon for femoropopliteal artery disease.
      • Tepe G.
      • Laird J.
      • Schneider P.
      • Brodmann M.
      • Krishnan P.
      • Micari A.
      • et al.
      Drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery disease: 12-month results from the IN.PACT SFA randomized trial.
      Drug-eluting balloons share three common components: a platform, an antiproliferative drug, and a drug carrier or an excipient. The aim of the drug is to reduce SMC proliferation, migration and ECM synthesis by interrupting the cell cycle. Currently the main drug used for a drug-eluting balloon for peripheral arterial disease (PAD) is paclitaxel, which is a cytotoxic drug.
      • Axel D.I.
      • Kunert W.
      • Göggelmann C.
      • Oberhoff M.
      • Herdeg C.
      • Küttner A.
      • et al.
      Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery.
      Since ISR is mainly due to intimal hyperplasia, PEB use could improve endovascular treatment outcomes for FP ISR treatment. Currently, few studies are available regarding PEB use for ISR FP treatment.
      • Liistro F.
      • Angioli P.
      • Porto I.
      • Ricci L.
      • Ducci K.
      • Grotti S.
      • et al.
      Paclitaxel-eluting balloon vs. standard angioplasty to reduce recurrent restenosis in diabetic patients with in-stent restenosis of the superficial femoral and proximal popliteal arteries: the DEBATE-ISR study.
      • Stabile E.
      • Virga V.
      • Salemme L.
      • Cioppa A.
      • Ambrosini V.
      • Sorropago G.
      • et al.
      Drug-eluting balloon for treatment of superficial femoral artery in-stent restenosis.
      • Krankenberg H.
      • Tübler T.
      • Ingwersen M.
      • Schlüter M.
      • Scheinert D.
      • Blessing E.
      • et al.
      Drug-coated balloon versus standard balloon for superficial femoral artery in-stent restenosis: the randomized Femoral Artery In-Stent Restenosis (FAIR) Trial.
      In a prospective national multicentre cohort, the outcomes after PEB repair for patients with FP ISR have been investigated.

      Methods

      Experimental design

      PLAISIR was a multicentre, French, prospective cohort study in which patients referred for PAD and presenting with FP ISR lesions were included from January 2012 to June 2013. Patients were enrolled in 10 centres. This registry was established to determine the safety and the feasibility of PEB for treating ISR FP lesions. Inclusion and exclusion criteria are summarised in Table 1. Patients had either one or two limbs treated. The local ethics committee approved the protocol and all patients gave their informed consent. The PLAISIR trial was declared to clinical.gov.trial (NCT01587482).
      Table 1Inclusion and exclusion criteria.
      Inclusion criteriaExclusion criteria
      Age ≥ 18 years old

      Symptomatic patient according to Rutherford Class 1, 2, 3, 4 or 5

      Clinical degradation by at least 1 Rutherford stage or absence of healing of all skin lesions

      Symptoms related to SFA ISR defined by PSVR > 2.4 within 3–24 months after SFA stenting of de novo atherosclerotic lesions. Each patient may have either one or both limbs treated in the study

      The target ISR lesion is fully contained between the origin of the SFA and distally the femoropopliteal crossover (crossing by SFA of medial rim of femur in the PA projection)

      Adequate SFA inflow and outflow either pre-existing or successfully re-established (outflow defined as patency of at least one infragenicular artery)

      The target lesion must not extend beyond the stent margin

      Successful crossing of the target lesion, inflow and outflow lesions with a guidewire

      Patient belongs to the French health care system

      Written informed consent
      No atheromatous disease

      Asymptomatic lesion

      Known allergies to heparin, aspirin, other anti-coagulant/antiplatelet therapies, and/or paclitaxel

      Acute limb ischaemia

      Patient on oral anticoagulation therapy

      Target lesion requires/has been pretreated with alternative therapy such as: DES, laser, atherectomy, cryoplasty, cutting/scoring balloon, etc.

      Life expectancy < 1 year

      Patient involved in another trial

      Refusing patient

      Pregnancy

      Patients receiving anticoagulation
      ISR = in-stent restenosis; PSVR = peak systolic velocity ratio; SFA = superficial femoral artery.

      Procedures

      Briefly, the procedure was performed under local, locoregional, or general anaesthesia. After a percutaneous femoral (ipsilateral or contralateral) or brachial approach, an arteriogram was performed. The lesion was catheterised. Predilatation was performed using a standard balloon. The standard balloon dimensions were chosen so that the nominal diameter was less than the nominal vessel diameter by 1 mm and the length did not exceed the ISR length. For a residual restenosis > 50%, a high pressure balloon could be used. In case of predilatation failure, the procedure was considered as a technical failure and recorded. Following a successful predilatation, a PEB (IN.PACT Admiral, Medtronic, Santa Rosa, CA, USA) was used. The PEB dimensions were chosen so that the nominal diameter was equal to the nominal vessel diameter and the length did not exceed the ISR length by more than 5–10 mm at each edge. In case of the use of two or more PEBs, a 1 cm PEB overlap was required. According to the Medtronic instructions for use (http://www.accessdata.fda.gov/cdrh_docs/pdf14/P140010c.pdf), the balloon was inflated for a minimum of 1 min at a maximum pressure of 12 atm. In case of flow limiting dissection or residual stenosis > 50%, a nitinol self expandable stent was implanted. Groin closure was accomplished by manual compression or by an arterial closure device at the discretion of the physician. All procedures were performed after a bolus of heparin at a dose of 50 IU/kg. Post-operatively, patients were prescribed aspirin (dose at the physician's discretion) and clopidogrel (75 mg/day) for 6 months, followed by one antiplatelet agent. When patients were already on oral anticoagulant treatment, no antiplatelet agent was added. Compliance with the medical treatment was checked at each clinical endpoint.

      Follow-up

      Patients were prospectively followed up on an outpatient basis. Major adverse cardiovascular events (MACE) were collected. Follow-up included medical examination, ankle brachial index (ABI) measurements, and duplex scan at 1, 3, 6, 9, 12, and 18 months. Pre-operative data, imaging parameters, intra-operative data, and post-operative events were recorded prospectively in a computerised database. Quality of life was evaluated prior to intervention, after intervention, and at 1 year. Each centre was monitored by the department of Nantes UHC research direction.
      Monitoring consisted of checking 100% of content for all files and 100% of patient informed consent.

      Endpoints

      The primary endpoint was clinically driven target lesion revascularisation (TLR) rate at 1 year. TLR was considered clinically driven in case of clinical degradation by at least 1 Rutherford stage or absence of healing of all skin lesions associated with a stenosis ≥ 50% at the stented site and/or a peak systolic velocity ratio (PSVR) ≥ 2.4. The angiographic patterns of ISR were defined according to the classification proposed by Tosaka as follows: class I (focal or multifocal restenosis < 5 cm), class II (diffuse restenosis > 5 cm) and class III (total occlusion).
      • Tosaka A.
      • Soga Y.
      • Iida O.
      • Ishihara T.
      • Hirano K.
      • Suzuki K.
      • et al.
      Classification and clinical impact of restenosis after femoropopliteal stenting.
      Secondary endpoints were target extremity revascularisation (TER), major adverse cardiovascular events, primary and secondary sustained clinical improvement (primary and secondary sustained clinical improvement was defined as a sustained upward shift of ≥ 1 category of the Rutherford classification for claudicants and by wound healing and rest pain resolution for patients in CLI, with or without the need for repeated TLR in surviving patients), primary and secondary patency, quality of life assessment by the EQ-5D questionnaire,
      • EuroQol Group
      EuroQol—a new facility for the measurement of health-related quality of life.
      device success, technical success, duration of hospital stay, Rutherford classification, and measurement of ABI at 1 year. Detailed definitions of outcomes are given below.
      TER expresses the frequency of the need for repeated procedures (endovascular or surgical) because of a problem arising remotely from the lesion initially treated, in surviving patients with a preserved limb. Major cardiovascular events included all deaths, major amputation, procedure related serious adverse events, and device failure or malfunction. Primary sustained clinical improvement was defined as a sustained upward shift of ≥ 1 category of the Rutherford classification for claudicants and by wound healing and rest pain resolution for patients with critical limb ischaemia (CLI), without the need for repeated TLR in surviving patients. Secondary sustained clinical improvement was defined as a sustained upward shift of ≥ 1 category of the Rutherford classification for claudicants and by wound healing and rest pain resolution for patients in CLI, including the need for repeated TLR in surviving patients. Primary patency was defined as patency without any re-intervention and with PSVR < 2.4. Secondary patency was defined as patency with PSVR < 2.4 with the assistance of re-intervention. Technical success was defined as achievement of a final residual diameter stenosis of < 30% on the completion angiogram. Device success was defined as success of drug delivery with balloon inflation, deflation and retrieval without rupture.

      Statistical analysis

      Results were reported prospectively on an intention-to-treat basis. Continuous variables were presented as mean ± SD or median (range), categorical variables as count and percentage. Demographic and comorbidity data were recorded per patient.
      TLR, TER, clinical sustained improvement and patency data were calculated on a per limb basis. Survival rate curves for outcomes were plotted and calculated using the Kaplan–Meier method. For patients who died before the final follow-up examination or for patients lost to follow-up, the status of the last follow-up examination was recorded. Wilcoxon tests were used to analyze quality of life assessment by EQ-5D questionnaire and ABI during follow-up. A p < 0.05 was considered statistically significant. Data were analysed using the SPSS software (SPSS Inc., Chicago, IL, USA).

      Results

      Demographic data

      Between January 2012 and June 2013, 53 patients (55 limbs) were included. After a blinded review, 10 patients were defined as protocol violation because they presented a major protocol deviation because the interval between the initial FP stenting and development of ISR was greater than 2 years. Consequently, 53 patients (55 limbs) were analysed on an intention-to-treat basis. Clinical characteristics at the time of re-intervention are summarised in Table 2. Briefly, indications for re-intervention included 48 limbs (87%) for claudication and seven limbs (13%) for CLI.
      Table 2Demographic characteristics.
      Variables53 patients
      Age, year (mean ± SD)69 (±12)
      Gender: male, n (%)42 (79)
      Active smoking, n (%)17 (32)
      Hypertension, n (%)43 (81)
      Diabetes mellitus, n (%)16 (30)
      Dyslipidemia, n (%)41 (77)
      Renal failure, n (%)5 (9)
      Coronary heart disease, n (%)16 (30)
      Statins, n (%)47 (89)
      ACE, n (%)24 (45)
      APT, n (%)53 (100)
      ACE = angiotensin converting enzyme; APT = antiplatelet treatment.

      Intra-operative and perioperative data

      Sixty-five percent (36 lesions) of the procedures were performed under local anaesthesia and sedation. General anaesthesia was the standard of care for endovascular peripheral arterial procedures in five centres (Table 3).
      Table 3Intra-operative data.
      Variables55 limbs
      Lesion length, mm (mean ± SD)86 ± 32
      Lesion diameter, mm (mean ± SD)6 ± 0.57
      Tosaka classification, n (%)
       Class I25 (45)
       Class II29 (53)
       Class III1 (2)
      Runoff vessels, n (%)
       18 (15)
       210 (18)
       337 (67)
      Approach, n (%)
       Antegrade22 (40)
       Crossover32 (58)
       Brachial1 (2)
      Number of PEB/limb, n (%)
       134 (62)
       216 (29)
       34 (7)
       41 (2)
      PEB inflation duration, seconds (mean)101 (range 60–480)
      Technical success, n (%)54 (98)
      Bailout stenting, n (%)1 (2)
      Closure devices use, n (%)22 (40)
      Treated concomitant lesions, n (%)12 (21)
      PEB = paclitaxel eluting balloon.
      The arterial approach was via the ipsilateral femoral artery in 40% (22 lesions), contralateral femoral artery with a crossover in 58% (32 lesions) and brachial artery in 2% (1 lesion) of the procedures. According to the Tosaka classification, ISR lesions were classified as class I in 46%, class II in 53%, and class III in 2%. Predilatation was performed using standard balloon inflations in 98% of the cases. The mean diameter of PEB used was 6 ± 0.57 mm, and the mean length of the PEB was 86 ± 32 mm. One PEB was used in 62% of the procedures, two in 29%, three in 7%, and four in 2%. The mean inflation time was 101 s (60–480 s). The technical success rate was 98%; in one case, a high pressure ballooning followed by PEB and then stenting was performed to cover adjacent dissections. The device success rate was 100%. Concomitant lesions were treated in 12 limbs (21%) (2 deep femoral arteries, 4 popliteal arteries, 6 superficial femoral arteries). An arterial closure device was used for 40% (22 procedures). The median hospital stay was 2 days (1–33 days). One patient remained hospitalised for 33 days after the procedure because of post-operative acute ischaemia. Indeed the patient presented an acute thrombosis of the target lesion. Bypass surgery was contraindicated because of patient comorbidity and a major amputation was performed. The patient died few days later from septicaemia at day 33. One month after the procedure, no patients were lost of follow-up. No other major adverse event or re-intervention was observed during the 30 day perioperative period.

      Midterm follow-up

      Three patients were lost of follow-up at 1 year after the procedure (M1, M7, M9). The median follow-up was 17 months (range 1–19 months). The total mortality rate was 4% (n = 2). One patient died during the hospital stay and another died during the follow-up period from heart rhythm disorder 18 months after the PEB procedures. Concerning the primary endpoint, the freedom from TLR rates at 12 and 18 months were both 90.2 ± 4.2% (Fig. 1A). Target lesion revascularisation was required in five patients. Two patients had a FP bypass at 6 and 7 months and one patient had a conventional balloon angioplasty at 9 months, and two patients had conventional angioplasty and bailout stenting at 6 and 12 months. At 12 and 18 months the freedom from TER rates were 87.7 ± 4.7% and 78.6 ± 6.1%, respectively (Fig. 1B). Target extremity revascularisation was necessary in 10 patients. Eight patients had endovascular treatment at 3 months (n = 2), 12 months (n = 3), and 18 months (n = 5), including one patient who had two endovascular treatments of the same lesion. Finally, one patient had a FP bypass at 6 months after having a stenting at 3 months. One patient had a minor amputation at 3 months. The change in Rutherford classification is presented in Fig. 2. At 12 and 18 months, 77% and 67% of the patients were asymptomatic, respectively. The primary and secondary sustained clinical improvements were 78.6 ± 5.7% and 92.0 ± 3.8% at 1 year and 63.2 ± 6.7% and 79.2 ± 5.9% at 18 months. The primary patency rates at 12 and 18 months were 83.7% and 78.1%, respectively. During follow-up, five (9%) cases of in-stent thrombosis and 12 (21.9%) cases of repeat ISR were observed. Mean ABI increased from baseline levels of 0.54 ± 0.37 to 0.96 ± 0.54 at 12 months (p < .001) and remained elevated at 0.92 ± 0.23 at 18 months (p = .01).
      Figure 1
      Figure 1Kaplan–Meyer curve for freedom from TLR (A) and freedom from TER (B). TER = target extremity revascularisation = TLR: target lesion revascularisation; N = limbs at risk.
      Concerning the assessment of quality of life, there was a trend to an improvement in quality of life self evaluation but it was not significant. The visual analog scale score increased from 65.8 ± 14.1 at baseline to 76.2 ± 16.3 at 12 months (p = .10) and 72.3 ± 17.7 at 18 months (p = .14).
      A sub-group analysis was performed to compare the 10 patients defined as protocol violation with the others; there was no statistically significant difference in terms of TLR (90.5 ± 4.5% vs. 88.9 ± 10.5%; p = .42), TER (90.5 ± 4.6% vs. 88.9 ± 0.5%; p = .42), survival (95.1 ± 3.4% vs. 100%; p = .49), primary (83.6 ± 5.7% vs. 77.8 ± 0.45%; p = .45), or secondary (92.7 ± 4.1% vs. 88.9 ± 10.5%; p = 0.52) clinical improvement.
      Tosaka class I (25 lesions) and class II lesions (29 lesions) were compared in terms of freedom from TLR at 1 year. There was no significant difference between these groups (87.1 ± 7.0% versus 92.7 ± 5.0%; p = .44)

      Discussion

      Despite routine balloon angioplasty remains the most frequently used method of treatment for FP ISR, midterm outcomes are marked by high rates of redo ISR and re-interventions.
      • Tosaka A.
      • Soga Y.
      • Iida O.
      • Ishihara T.
      • Hirano K.
      • Suzuki K.
      • et al.
      Classification and clinical impact of restenosis after femoropopliteal stenting.
      In this prospective French multicentre study cohort, PEB used for treatment of FP ISR showed promising results in terms of freedom from TLR and sustained clinical improvement.

      Comparing to other DCB studies

      The use of paclitaxel as an anti-proliferative drug has already shown interesting results superior to conventional PTA in de novo and restenotic FP lesions.
      • Tepe G.
      • Laird J.
      • Schneider P.
      • Brodmann M.
      • Krishnan P.
      • Micari A.
      • et al.
      Drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery disease: 12-month results from the IN.PACT SFA randomized trial.
      • Micari A.
      • Cioppa A.
      • Vadalà G.
      • Castriota F.
      • Liso A.
      • Marchese A.
      • et al.
      2-year results of paclitaxel-eluting balloons for femoropopliteal artery disease: evidence from a multicenter registry.
      • Scheinert D.
      • Schulte K.-L.
      • Zeller T.
      • Lammer J.
      • Tepe G.
      Paclitaxel-releasing balloon in femoropopliteal lesions using a BTHC excipient: twelve-month results from the BIOLUX P-I randomized trial.
      • Schroeder H.
      • Meyer D.-R.
      • Lux B.
      • Ruecker F.
      • Martorana M.
      • Duda S.
      Two-year results of a low-dose drug-coated balloon for revascularization of the femoropopliteal artery: outcomes from the ILLUMENATE first-in-human study.
      • Werk M.
      • Albrecht T.
      • Meyer D.-R.
      • Ahmed M.N.
      • Behne A.
      • Dietz U.
      • et al.
      Paclitaxel-coated balloons reduce restenosis after femoro-popliteal angioplasty: evidence from the randomized PACIFIER trial.
      In this study, the use of PEB for treating FP ISR showed promising results in terms of absence of TLR, primary patency, and sustained clinical improvement. The results are similar to other studies dealing with the same type and localisation of lesions. In 2012, Stabile et al.
      • Stabile E.
      • Virga V.
      • Salemme L.
      • Cioppa A.
      • Ambrosini V.
      • Sorropago G.
      • et al.
      Drug-eluting balloon for treatment of superficial femoral artery in-stent restenosis.
      showed a primary patency rate of 92.1% at 1 year and a freedom from TLR rate of 100%. In the DEBATE-ISR study in 2014, Liistro et al.
      • Liistro F.
      • Angioli P.
      • Porto I.
      • Ricci L.
      • Ducci K.
      • Grotti S.
      • et al.
      Paclitaxel-eluting balloon vs. standard angioplasty to reduce recurrent restenosis in diabetic patients with in-stent restenosis of the superficial femoral and proximal popliteal arteries: the DEBATE-ISR study.
      showed a primary patency rate at 1 year of 81.5% and a freedom from TLR rate of 86.4%. In the present study lesion length was similar to that of the study of Stabile (82.9 mm vs. 86 mm), but shorter than the length reported in DEBATE-ISR study (132 mm vs. 86 mm). In 2014, the FAIR study compared plain balloon angioplasty (POBA) and PEB in the treatment of medium length FP lesions (82.3 mm).
      • Krankenberg H.
      • Tübler T.
      • Ingwersen M.
      • Schlüter M.
      • Scheinert D.
      • Blessing E.
      • et al.
      Drug-coated balloon versus standard balloon for superficial femoral artery in-stent restenosis: the randomized Femoral Artery In-Stent Restenosis (FAIR) Trial.
      Sixty-two patients were randomised in the PEB group and 57 in the POBA group. This study showed a superiority of PEB over POBA in terms of TLR rates at 1 year (90.8% versus 52.6%; p = .001) and primary patency at 1 year (70.5% vs. 37.5%; p = .004).

      Why paclitaxel?

      So far, only paclitaxel is used for peripheral drug-eluting balloons. The paclitaxel is a hydrophobic and lipophilic drug with a rapid absorption and an extended anti-proliferative effect that made it the most efficient drug for drug-eluting balloons.
      • Axel D.I.
      • Kunert W.
      • Göggelmann C.
      • Oberhoff M.
      • Herdeg C.
      • Küttner A.
      • et al.
      Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery.
      Because of its hydrophilic characteristic sirolimus seems less suitable. Indeed an important part of the drug would be washed out during transit in the vessel and consequently lost and not able to penetrate the arterial wall. Although all drug-eluting balloons used paclitaxel, a class effect cannot be established for PEBs for FP ISR restenosis repair. Indeed, there are many factors such as components and manufacturing process that differ among PEBs. Unfortunately, there is no direct comparison between two different PEBs for the same vessel bed, although in the coronary artery disease literature there are studies that directly compare different PEBs. In 2012, a Swedish study compared the results of a first and second generation PEB.
      • Bondesson P.
      • Lagerqvist B.
      • James S.K.
      • Olivecrona G.K.
      • Venetsanos D.
      • Harnek J.
      Comparison of two drug-eluting balloons: a report from the SCAAR registry.
      The Aachen Elutax balloon (ARE) (Aachen Resonnance GmbH., Aachen, Germany) is a first generation PEB and uses paclitaxel in a concentration of 2 μg/mm2, without a drug carrier. The Braun Sequent Please balloon (BSP) (B. Braun AG Melsunden, Germany) is a second generation PEB. It uses paclitaxel at a concentration of 3 μg/mm2 in a matrix with iopromide. Over the whole follow-up period, the rate of restenosis was lower in BSP compared to ARE (HR = 0.42 IC 95% 0.26–0.68) which was in favour of no class effect for drug-eluting balloon for coronary artery disease.

      Comparing with other devices

      Drug-eluting devices are particularly appealing to prevent and to treat ISR. In the Zilver-PTX single arm study that evaluated the results of a drug-eluting device (drug-eluting stent) for FP lesions, 130 (14.4%) restenotic lesions were also included. Drug-eluting stents showed a primary patency rate of 79% and a freedom from TLR at 1 year of 81% after treatment of 119 lesions in 108 patients.
      • Dake M.D.
      • Scheinert D.
      • Tepe G.
      • Tessarek J.
      • Fanelli F.
      • Bosiers M.
      • et al.
      Nitinol stents with polymer-free paclitaxel coating for lesions in the superficial femoral and popliteal arteries above the knee: twelve-month safety and effectiveness results from the Zilver PTX single-arm clinical study.
      However, drug-eluting stent indications for ISR are questionable. Indeed, because the main cause of ISR is SMC migration, proliferation, and synthesis, the need for scaffolding does not represent an issue to treat ISR. Moreover, stent superposition could also lead to the lumen loss. All these points support the fact, particularly for ISR, that a no-stent strategy should be preferred (Table 4).
      Table 4Comparison of published freedom from TLR and primary patency following treatment of FP.
      Study/first authorDevicesFollow-upLesions (n)Freedom from TLRPrimary patency
      Zilver-PTX
      • Dake M.D.
      • Scheinert D.
      • Tepe G.
      • Tessarek J.
      • Fanelli F.
      • Bosiers M.
      • et al.
      Nitinol stents with polymer-free paclitaxel coating for lesions in the superficial femoral and popliteal arteries above the knee: twelve-month safety and effectiveness results from the Zilver PTX single-arm clinical study.
      DES1 year10881%79%
      RELINE study
      • Bosiers M.
      • Deloose K.
      • Callaert J.
      • Verbist J.
      • Hendriks J.
      • Lauwers P.
      • et al.
      Superiority of stent-grafts for in-stent restenosis in the superficial femoral artery: twelve-month results from a multicenter randomized trial.
      Viabahn covered stent1 year3980%74%
      PTA1 year4442%28%
      Werner et al.
      • Werner M.
      • Scheinert D.
      • Henn M.
      • Scheinert S.
      • Bräunlich S.
      • Bausback Y.
      • et al.
      Endovascular brachytherapy using liquid Beta-emitting rhenium-188 for the treatment of long-segment femoropopliteal in-stent stenosis.
      Brachytherapy1 year90NS80%
      Dick et al.
      • Dick P.
      • Sabeti S.
      • Mlekusch W.
      • Schlager O.
      • Amighi J.
      • Haumer M.
      • et al.
      Conventional balloon angioplasty versus peripheral cutting balloon angioplasty for treatment of femoropopliteal artery in-stent restenosis: initial experience.
      Cutting balloon6 months1759%35%
      PTA6 months2264%27%
      Shammas et al.
      • Shammas N.W.
      • Shammas G.A.
      • Helou T.J.
      • Voelliger C.M.
      • Mrad L.
      • Jerin M.
      Safety and 1-year revascularization outcome of SilverHawk atherectomy in treating in-stent restenosis of femoropopliteal arteries: a retrospective review from a single center.
      Directional atherectomy1 year4166%NS
      Trentmann et al.
      • Trentmann J.
      • Charalambous N.
      • Djawanscher M.
      • Schäfer J.-P.
      • Jahnke T.
      Safety and efficacy of directional atherectomy for the treatment of in-stent restenosis of the femoropopliteal artery.
      Directional atherectomy1 year35NS25%
      Zeller et al.
      • Zeller T.
      • Rastan A.
      • Sixt S.
      • Schwarzwälder U.
      • Schwarz T.
      • Frank U.
      • et al.
      Long-term results after directional atherectomy of femoro-popliteal lesions.
      Directional atherectomy1 year4353%54%
      Shammas et al.
      • Shammas N.W.
      • Shammas G.A.
      • Hafez A.
      • Kelly R.
      • Reynolds E.
      • Shammas A.N.
      Safety and one-year revascularization outcome of excimer laser ablation therapy in treating in-stent restenosis of femoropopliteal arteries: a retrospective review from a single center.
      Laser atherectomy + PTA1 year4049%NS
      Yeo et al.
      • Yeo K.-K.
      • Malik U.
      • Laird J.R.
      Outcomes following treatment of femoropopliteal in-stent restenosis: a single center experience.
      Laser atherectomy + PTA1 year2277%NS
      Excite ISR study
      • Dippel E.J.
      • Makam P.
      • Kovach R.
      • George J.C.
      • Patlola R.
      • Metzger D.C.
      • et al.
      Randomized controlled study of excimer laser atherectomy for treatment of femoropopliteal in-stent restenosis: initial results from the EXCITE ISR trial (EXCImer Laser Randomized Controlled Study for Treatment of FemoropopliTEal In-Stent Restenosis).
      Laser atherectomy + PTA6 months16973.5%NS
      PTA6 months8151.8%NS
      Laird et al.
      • Laird J.R.
      • Yeo K.K.
      • Rocha-Singh K.
      • Das T.
      • Joye J.
      • Dippel E.
      • et al.
      Excimer laser with adjunctive balloon angioplasty and heparin-coated self-expanding stent grafts for the treatment of femoropopliteal artery in-stent restenosis: twelve-month results from the SALVAGE study.
      Laser atherectomy + heparin coated stent1 year2783%48%
      Van den Berg et al.
      • Van den Berg J.C.
      • Pedrotti M.
      • Canevascini R.
      • Chimchila Chevili S.
      • Giovannacci L.
      • Rosso R.
      In-stent restenosis: mid-term results of debulking using excimer laser and drug-eluting balloons: sustained benefit?.
      Laser atherectomy + DEB18 months1486%86%
      Stabile et al.
      • Stabile E.
      • Virga V.
      • Salemme L.
      • Cioppa A.
      • Ambrosini V.
      • Sorropago G.
      • et al.
      Drug-eluting balloon for treatment of superficial femoral artery in-stent restenosis.
      DEB1 year39100%92.1%
      DEBATE ISR study
      • Liistro F.
      • Angioli P.
      • Porto I.
      • Ricci L.
      • Ducci K.
      • Grotti S.
      • et al.
      Paclitaxel-eluting balloon vs. standard angioplasty to reduce recurrent restenosis in diabetic patients with in-stent restenosis of the superficial femoral and proximal popliteal arteries: the DEBATE-ISR study.
      DEB1 year4486.4%81.5%
      DEBATE ISR study
      • Grotti S.
      • Liistro F.
      • Angioli P.
      • Ducci K.
      • Falsini G.
      • Porto I.
      • et al.
      Paclitaxel-eluting balloon vs standard angioplasty to reduce restenosis in diabetic patients with in-stent restenosis of the superficial femoral and proximal popliteal arteries: three-year results of the DEBATE-ISR Study.
      DEB3 year4460%NS
      FAIR study
      • Krankenberg H.
      • Tübler T.
      • Ingwersen M.
      • Schlüter M.
      • Scheinert D.
      • Blessing E.
      • et al.
      Drug-coated balloon versus standard balloon for superficial femoral artery in-stent restenosis: the randomized Femoral Artery In-Stent Restenosis (FAIR) Trial.
      DEB1 year6290.8%70.5%
      PTA1 year5752.8%37.5%
      PLAISIR studyDEB1 year5590.2%83.7%
      DEB = drug-eluting balloon; DES = drug-eluting stent; FP = femoropopliteal; ISR = in-stent restenosis; PTA = percutaneous transluminal angioplasty.
      Others have evaluated debulking devices to treat in-stent restenosis. PEB results seem better than those obtained with directional atherectomy.
      • Shammas N.W.
      • Shammas G.A.
      • Helou T.J.
      • Voelliger C.M.
      • Mrad L.
      • Jerin M.
      Safety and 1-year revascularization outcome of SilverHawk atherectomy in treating in-stent restenosis of femoropopliteal arteries: a retrospective review from a single center.
      • Trentmann J.
      • Charalambous N.
      • Djawanscher M.
      • Schäfer J.-P.
      • Jahnke T.
      Safety and efficacy of directional atherectomy for the treatment of in-stent restenosis of the femoropopliteal artery.
      • Zeller T.
      • Rastan A.
      • Sixt S.
      • Schwarzwälder U.
      • Schwarz T.
      • Frank U.
      • et al.
      Long-term results after directional atherectomy of femoro-popliteal lesions.
      In those studies, the primary patency rate and freedom from TLR at 1 year ranged from 25% to 54% and from 53% to 56%, respectively. A cutting balloon could be also an option to treat in-stent restenosis. But so far, cutting balloons have failed to prove superiority when compared with conventional PTA.
      • Dick P.
      • Sabeti S.
      • Mlekusch W.
      • Schlager O.
      • Amighi J.
      • Haumer M.
      • et al.
      Conventional balloon angioplasty versus peripheral cutting balloon angioplasty for treatment of femoropopliteal artery in-stent restenosis: initial experience.
      Indeed, the primary patency rate at 1 year was 35% and freedom from TLR was 59%.
      With laser atherectomy and PTA, the primary patency rate is 48%, and freedom from TLR rates range from 49% to 77%.
      • Shammas N.W.
      • Shammas G.A.
      • Hafez A.
      • Kelly R.
      • Reynolds E.
      • Shammas A.N.
      Safety and one-year revascularization outcome of excimer laser ablation therapy in treating in-stent restenosis of femoropopliteal arteries: a retrospective review from a single center.
      • Yeo K.-K.
      • Malik U.
      • Laird J.R.
      Outcomes following treatment of femoropopliteal in-stent restenosis: a single center experience.
      The Excite ISR study compared laser and PTA versus PTA alone. At 6 months the freedom from TLR rates were 73.5% for the laser and PTA group (169 patients) versus 51.8% for the PTA alone group (81 patients) (p < .005).
      • Dippel E.J.
      • Makam P.
      • Kovach R.
      • George J.C.
      • Patlola R.
      • Metzger D.C.
      • et al.
      Randomized controlled study of excimer laser atherectomy for treatment of femoropopliteal in-stent restenosis: initial results from the EXCITE ISR trial (EXCImer Laser Randomized Controlled Study for Treatment of FemoropopliTEal In-Stent Restenosis).
      Laser atherectomy in association with heparin coated stent grafts showed promising results for the treatment of FP ISR. In 2012, Laird et al.
      • Laird J.R.
      • Yeo K.K.
      • Rocha-Singh K.
      • Das T.
      • Joye J.
      • Dippel E.
      • et al.
      Excimer laser with adjunctive balloon angioplasty and heparin-coated self-expanding stent grafts for the treatment of femoropopliteal artery in-stent restenosis: twelve-month results from the SALVAGE study.
      evaluated laser atherectomy with heparin coated stent grafts for FP ISR repair. In this study, the 1 year primary patency rate was 48%, but freedom from the 1 year TLR rate was 83%. Those results were similar to those obtained with PEB and drug-eluting stents. Only one study evaluated Laser atherectomy with DEB in the treatment of in-stent restenosis. In 2014, Van den Berg et al.
      • Van den Berg J.C.
      • Pedrotti M.
      • Canevascini R.
      • Chimchila Chevili S.
      • Giovannacci L.
      • Rosso R.
      In-stent restenosis: mid-term results of debulking using excimer laser and drug-eluting balloons: sustained benefit?.
      showed a primary patency rate and a freedom from TLR rate of 86% at 18 months. This result can suggest that laser atherectomy did not improve DEB angioplasty efficacy in the treatment of ISR. Brachytherapy also showed results for the treatment of this type of lesions. In 2012, Werner et al.
      • Werner M.
      • Scheinert D.
      • Henn M.
      • Scheinert S.
      • Bräunlich S.
      • Bausback Y.
      • et al.
      Endovascular brachytherapy using liquid Beta-emitting rhenium-188 for the treatment of long-segment femoropopliteal in-stent stenosis.
      found a primary patency rate at one year of 79.8% after treatment of 90 consecutive patients suffering from symptomatic FP ISR. However, the cost and the ease of using brachytherapy as a therapeutic option have considerably limited the uptake of this technique.
      In 2015, the Reline study compared treatment of superficial femoral artery (SFA) ISR using plain balloon angioplasty or the Viabahn covered stent (Gore & Associates, Flagstaff, AZ, USA).
      • Bosiers M.
      • Deloose K.
      • Callaert J.
      • Verbist J.
      • Hendriks J.
      • Lauwers P.
      • et al.
      Superiority of stent-grafts for in-stent restenosis in the superficial femoral artery: twelve-month results from a multicenter randomized trial.
      Thirty-nine patients were randomised in the Viabahn group and 44 in the plain balloon angioplasty group. This study showed superiority of the Viabahn in the treatment of SFA ISR in terms of primary patency at 1 year (74.8% vs. 28%; p < .001) and in terms of freedom from TLR at 1 year (80% vs. 42%; p < .001).

      Factors influencing the results

      Many factors are supposed to influence PEB efficacy for the treatment of FP ISR. This study was not designed to identify patient or lesion characteristics that can influence PEB results. Other studies are needed to identify these factors including diabetes, calcification, type of drug, drug concentration, balloon design, excipient, and Tosaka classification. Tosaka showed that the rate of recurrent ISR differs according to the type of ISR. Indeed, at 2 years ISR occurrence was 84.8% in class III patients compared with 49.9% in class I patients (p < .0001) and 53.3% in class II patients (p = .0003). Moreover the rate of recurrent occlusion at 2 years was 64.6% in class III patients compared with 15.9% in class I patients (p < .0001) and 18.9% in class II patients (p < .0001).
      • Tosaka A.
      • Soga Y.
      • Iida O.
      • Ishihara T.
      • Hirano K.
      • Suzuki K.
      • et al.
      Classification and clinical impact of restenosis after femoropopliteal stenting.
      But in 2012, Stabile et al.
      • Stabile E.
      • Virga V.
      • Salemme L.
      • Cioppa A.
      • Ambrosini V.
      • Sorropago G.
      • et al.
      Drug-eluting balloon for treatment of superficial femoral artery in-stent restenosis.
      did not show such differences in terms of recurrence of restenosis according the Tosaka classification. This study did not show a difference in terms of freedom from TLR between Tosaka class I and class II restenosis.
      Diabetes could be a limiting factor for PEB efficacy. In 2016, Grotti et al.
      • Grotti S.
      • Liistro F.
      • Angioli P.
      • Ducci K.
      • Falsini G.
      • Porto I.
      • et al.
      Paclitaxel-eluting balloon vs standard angioplasty to reduce restenosis in diabetic patients with in-stent restenosis of the superficial femoral and proximal popliteal arteries: three-year results of the DEBATE-ISR Study.
      showed that at 3 year follow-up (the DEBATE-ISR study) TLR rates were 40% in the DEB group versus 43% in the standard angioplasty group. They confirmed that Tosaka class III occlusion was associated with a worse outcome in both study groups (odds ratio 3.96, 95% CI 1.55– to 10.1, p = .004).
      This study seems to show that the delay in the occurrence of restenosis did not influence drug-coated balloon results.

      Study limitations

      The main limitation of this study was the absence of a control group and the relatively small sample size, both of which limit the statistical significance of the conclusions. However, the inclusion and exclusion criteria were not strictly observed. Indeed, a blinded review decided to define 10 patients as protocol violation. For all of them, FP ISR was noted to occur 2 years after the initial stent implantation, which was an exclusion criteria. This is because 2 years after stent implantation the development of new lesions was more related to the evolution of atheromatous disease than the intimal hyperplasia.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Suzuki K.
      • Hirano K.
      • Kawasaki D.
      • et al.
      Shared and differential factors influencing restenosis following endovascular therapy between TASC (Trans-Atlantic Inter-Society Consensus) II class A to C and D lesions in the femoropopliteal artery.
      • Schillinger M.
      • Minar E.
      Past, present and future of femoropopliteal stenting.

      Conclusion

      This study shows that PEB could be an effective and safe treatment for FP ISR. Further randomised and controlled studies are needed to confirm those encouraging results and to define the new standard of care for FP ISR.

      Conflict of Interest

      Antoine Sauguet received consulting fees from Abbott Vascular, Boston Scientific, and Medtronic. Philippe Commeau received consulting fees from BSCI, Abbott, Terumo, and Cordis. Yann Gouëffic received consulting fees and a travel grant from Cook, Medtronic, Pérouse, and Terumo.

      Funding

      Medtronic (92100 Boulogne-Billancourt, France) funded the PLAISIR trial.

      References

        • Hoffmann R.
        • Mintz G.S.
        • Dussaillant G.R.
        • Popma J.J.
        • Pichard A.D.
        • Satler L.F.
        • et al.
        Patterns and mechanisms of in-stent restenosis. A serial intravascular ultrasound study.
        Circulation. 1996; 94: 1247-1254
        • Tosaka A.
        • Soga Y.
        • Iida O.
        • Ishihara T.
        • Hirano K.
        • Suzuki K.
        • et al.
        Classification and clinical impact of restenosis after femoropopliteal stenting.
        J Am Coll Cardiol. 2012; 59: 16-23
        • Shammas N.W.
        • Shammas G.A.
        • Helou T.J.
        • Voelliger C.M.
        • Mrad L.
        • Jerin M.
        Safety and 1-year revascularization outcome of SilverHawk atherectomy in treating in-stent restenosis of femoropopliteal arteries: a retrospective review from a single center.
        Cardiovasc Revascularization Med Mol Interv. 2012; 13: 224-227
        • Trentmann J.
        • Charalambous N.
        • Djawanscher M.
        • Schäfer J.-P.
        • Jahnke T.
        Safety and efficacy of directional atherectomy for the treatment of in-stent restenosis of the femoropopliteal artery.
        J Cardiovasc Surg (Torino). 2010; 51: 551-560
        • Zeller T.
        • Rastan A.
        • Sixt S.
        • Schwarzwälder U.
        • Schwarz T.
        • Frank U.
        • et al.
        Long-term results after directional atherectomy of femoro-popliteal lesions.
        J Am Coll Cardiol. 2006; 48: 1573-1578
        • Dick P.
        • Sabeti S.
        • Mlekusch W.
        • Schlager O.
        • Amighi J.
        • Haumer M.
        • et al.
        Conventional balloon angioplasty versus peripheral cutting balloon angioplasty for treatment of femoropopliteal artery in-stent restenosis: initial experience.
        Radiology. 2008; 248: 297-302
        • Werner M.
        • Scheinert D.
        • Henn M.
        • Scheinert S.
        • Bräunlich S.
        • Bausback Y.
        • et al.
        Endovascular brachytherapy using liquid Beta-emitting rhenium-188 for the treatment of long-segment femoropopliteal in-stent stenosis.
        J Endovasc. 2012; 19: 467-475
        • Shammas N.W.
        • Shammas G.A.
        • Hafez A.
        • Kelly R.
        • Reynolds E.
        • Shammas A.N.
        Safety and one-year revascularization outcome of excimer laser ablation therapy in treating in-stent restenosis of femoropopliteal arteries: a retrospective review from a single center.
        Cardiovasc Revasc Med. 2012; 13: 341-344
        • Yeo K.-K.
        • Malik U.
        • Laird J.R.
        Outcomes following treatment of femoropopliteal in-stent restenosis: a single center experience.
        Catheter Cardiovasc Interv. 2011; 78: 604-608
        • Laird J.R.
        • Yeo K.K.
        • Rocha-Singh K.
        • Das T.
        • Joye J.
        • Dippel E.
        • et al.
        Excimer laser with adjunctive balloon angioplasty and heparin-coated self-expanding stent grafts for the treatment of femoropopliteal artery in-stent restenosis: twelve-month results from the SALVAGE study.
        Catheter Cardiovasc Interv. 2012; 80: 852-859
        • Dippel E.J.
        • Makam P.
        • Kovach R.
        • George J.C.
        • Patlola R.
        • Metzger D.C.
        • et al.
        Randomized controlled study of excimer laser atherectomy for treatment of femoropopliteal in-stent restenosis: initial results from the EXCITE ISR trial (EXCImer Laser Randomized Controlled Study for Treatment of FemoropopliTEal In-Stent Restenosis).
        JACC Cardiovasc Interv. 2015; 8: 92-101
        • Bosiers M.
        • Deloose K.
        • Callaert J.
        • Verbist J.
        • Hendriks J.
        • Lauwers P.
        • et al.
        Superiority of stent-grafts for in-stent restenosis in the superficial femoral artery: twelve-month results from a multicenter randomized trial.
        J Endovasc Ther. 2015; 22: 1-10
        • Dake M.D.
        • Scheinert D.
        • Tepe G.
        • Tessarek J.
        • Fanelli F.
        • Bosiers M.
        • et al.
        Nitinol stents with polymer-free paclitaxel coating for lesions in the superficial femoral and popliteal arteries above the knee: twelve-month safety and effectiveness results from the Zilver PTX single-arm clinical study.
        J Endovasc Ther. 2011; 18: 613-623
        • Rosenfield K.
        • Jaff M.R.
        • White C.J.
        • Rocha-Singh K.
        • Mena-Hurtado C.
        • Metzger D.C.
        • et al.
        Trial of a paclitaxel-coated balloon for femoropopliteal artery disease.
        N Engl J Med. 2015; 373: 145-153
        • Tepe G.
        • Laird J.
        • Schneider P.
        • Brodmann M.
        • Krishnan P.
        • Micari A.
        • et al.
        Drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery disease: 12-month results from the IN.PACT SFA randomized trial.
        Circulation. 2015; 131: 495-502
        • Axel D.I.
        • Kunert W.
        • Göggelmann C.
        • Oberhoff M.
        • Herdeg C.
        • Küttner A.
        • et al.
        Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery.
        Circulation. 1997; 96: 636-645
        • Liistro F.
        • Angioli P.
        • Porto I.
        • Ricci L.
        • Ducci K.
        • Grotti S.
        • et al.
        Paclitaxel-eluting balloon vs. standard angioplasty to reduce recurrent restenosis in diabetic patients with in-stent restenosis of the superficial femoral and proximal popliteal arteries: the DEBATE-ISR study.
        J Endovasc Ther. 2014; 21: 1-8
        • Stabile E.
        • Virga V.
        • Salemme L.
        • Cioppa A.
        • Ambrosini V.
        • Sorropago G.
        • et al.
        Drug-eluting balloon for treatment of superficial femoral artery in-stent restenosis.
        J Am Coll Cardiol. 2012; 60: 1739-1742
        • Krankenberg H.
        • Tübler T.
        • Ingwersen M.
        • Schlüter M.
        • Scheinert D.
        • Blessing E.
        • et al.
        Drug-coated balloon versus standard balloon for superficial femoral artery in-stent restenosis: the randomized Femoral Artery In-Stent Restenosis (FAIR) Trial.
        Circulation. 2015; 132: 2230-2236
        • EuroQol Group
        EuroQol—a new facility for the measurement of health-related quality of life.
        Health Policy. 1990; 16: 199-208
        • Micari A.
        • Cioppa A.
        • Vadalà G.
        • Castriota F.
        • Liso A.
        • Marchese A.
        • et al.
        2-year results of paclitaxel-eluting balloons for femoropopliteal artery disease: evidence from a multicenter registry.
        JACC Cardiovasc Interv. 2013; 6: 282-289
        • Scheinert D.
        • Schulte K.-L.
        • Zeller T.
        • Lammer J.
        • Tepe G.
        Paclitaxel-releasing balloon in femoropopliteal lesions using a BTHC excipient: twelve-month results from the BIOLUX P-I randomized trial.
        J Endovasc Ther. 2015; 22: 14-21
        • Schroeder H.
        • Meyer D.-R.
        • Lux B.
        • Ruecker F.
        • Martorana M.
        • Duda S.
        Two-year results of a low-dose drug-coated balloon for revascularization of the femoropopliteal artery: outcomes from the ILLUMENATE first-in-human study.
        Catheter Cardiovasc Interv. 2015; 86: 278-286
        • Werk M.
        • Albrecht T.
        • Meyer D.-R.
        • Ahmed M.N.
        • Behne A.
        • Dietz U.
        • et al.
        Paclitaxel-coated balloons reduce restenosis after femoro-popliteal angioplasty: evidence from the randomized PACIFIER trial.
        Circ Cardiovasc Interv. 2012; 5: 831-840
        • Bondesson P.
        • Lagerqvist B.
        • James S.K.
        • Olivecrona G.K.
        • Venetsanos D.
        • Harnek J.
        Comparison of two drug-eluting balloons: a report from the SCAAR registry.
        EuroIntervention. 2012; 8: 444-449
        • Van den Berg J.C.
        • Pedrotti M.
        • Canevascini R.
        • Chimchila Chevili S.
        • Giovannacci L.
        • Rosso R.
        In-stent restenosis: mid-term results of debulking using excimer laser and drug-eluting balloons: sustained benefit?.
        J Invasive Cardiol. 2014; 26: 333-337
        • Grotti S.
        • Liistro F.
        • Angioli P.
        • Ducci K.
        • Falsini G.
        • Porto I.
        • et al.
        Paclitaxel-eluting balloon vs standard angioplasty to reduce restenosis in diabetic patients with in-stent restenosis of the superficial femoral and proximal popliteal arteries: three-year results of the DEBATE-ISR Study.
        J Endovasc Ther. 2016; 23: 52-57
        • Iida O.
        • Takahara M.
        • Soga Y.
        • Suzuki K.
        • Hirano K.
        • Kawasaki D.
        • et al.
        Shared and differential factors influencing restenosis following endovascular therapy between TASC (Trans-Atlantic Inter-Society Consensus) II class A to C and D lesions in the femoropopliteal artery.
        JACC Cardiovasc Interv. 2014; 7: 792-798
        • Schillinger M.
        • Minar E.
        Past, present and future of femoropopliteal stenting.
        J Endovasc Ther. 2009; 16: I147-I152

      Comments

      Commenting Guidelines

      To submit a comment for a journal article, please use the space above and note the following:

      • We will review submitted comments as soon as possible, striving for within two business days.
      • This forum is intended for constructive dialogue. Comments that are commercial or promotional in nature, pertain to specific medical cases, are not relevant to the article for which they have been submitted, or are otherwise inappropriate will not be posted.
      • We require that commenters identify themselves with names and affiliations.
      • Comments must be in compliance with our Terms & Conditions.
      • Comments are not peer-reviewed.