DOI: 10.1148/radiol.2481071159
(Radiology 2008;248:297-302.)
© RSNA, 2008
Vascular and Interventional Radiology |
Conventional Balloon Angioplasty versus Peripheral Cutting Balloon Angioplasty for Treatment of Femoropopliteal Artery In-Stent Restenosis: Initial Experience1
Petra Dick, MD,
Schila Sabeti, MD,
Wolfgang Mlekusch, MD,
Oliver Schlager, MD,
Jasmin Amighi, MD,
Markus Haumer, MD,
Manfred Cejna, MD,
Erich Minar, MD, and
Martin Schillinger, MD
1 From the Department of Internal Medicine II, Division of Angiology, Vienna General Hospital, Medical School, Waehringer Guertel 18-20, A-1090 Vienna, Austria. Received July 3, 2007; revision requested September 3; revision received September 24; accepted December 6; final version accepted December 20.
Address correspondence to M.S. (e-mail: martin.schillinger{at}meduniwien.ac.at).
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ABSTRACT
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Purpose: To prospectively determine whether cutting balloon angioplasty, when compared with conventional balloon angioplasty (CBA), improves morphologic and clinical outcome in patients with femoropopliteal in-stent restenosis.
Materials and Methods: Patients with symptomatic femoropopliteal in-stent restenosis were randomly assigned to undergo CBA or peripheral cutting balloon angioplasty (PCBA) for treatment of lesions up to 20 cm in length. Patients were followed up clinically and with duplex ultrasonography (US) at 1, 3, and 6 months for occurrence of a restenosis of 50% or higher. The Fisher exact test and Mann Whitney U test were used for statistical analyses.
Results: Forty patients were enrolled; one patient was lost to follow-up. In the remaining patients, CBA was performed in 22 patients; PCBA was used in 17 patients. Average lesion length was 80 mm ± 68 (standard deviation). Restenosis rates at 6 months were 65% (11 of 17; 95% confidence interval: 42%, 88%) after PCBA versus 73% (16 of 22; 95% confidence interval: 54%, 92%) after CBA (P = .73). Ankle brachial index (0.83 vs 0.75, P = .26) and maximum walking capacity on the treadmill (117 m vs 103 m, P = .97) at 6 months were also not significantly different between the two groups.
Conclusion: PCBA failed to prove superiority compared with CBA for treatment of femoropopliteal in-stent restenosis in this pilot study. In restenotic lesions with an average length of approximately 8 cm, both treatment modalities yielded disappointing 6-month patency rates.
© RSNA, 2008
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INTRODUCTION
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Endovascular stents resolve the problems of elastic recoil, residual stenosis, and flow-limiting dissection, and recently, self-expanding nitinol stents have been demonstrated to improve patency of the superficial femoral artery up to 2 years after intervention, compared with balloon angioplasty (1,2). However, exaggerated neointimal hyperplasia leading to in-stent restenosis still remains a major drawback and occurs even with nitinol stents in 20%–40% of patients at 2 years (2,3). With increasing numbers of stents implanted, management of in-stent restenosis becomes a growing problem. Repeated conventional balloon angioplasty (CBA) of in-stent restenosis is technically feasible and mostly yields acceptable immediate results. Unfortunately, the short- and midterm rates of recurrent failure after repeat CBA of in-stent restenosis remain high (4).
The concept of peripheral cutting balloon angioplasty (PCBA) seems appealing for the indication of in-stent restenosis, as the balloon-mounted microtomes guarantee smooth lumen gain in the stent without the risk of vessel wall perforation owing to the protecting effect of the stent struts. Initial reports on the use of PCBA for the treatment of occlusive atherosclerotic disease of the superior femoral artery showed promising results (5,6), in particular, the problem of elastic recoil seems to be ideally addressed with the cutting balloon. A reduction of vessel wall trauma by controlled incision with the cutting balloon device may translate into less vascular inflammation and consequently, reduced neointima formation, as shown in coronary de novo lesions (7).
We hypothesized that PCBA may cause less vascular inflammation in response to injury and thus yields improved morphologic and clinical outcomes when compared with CBA for treatment of femoropopliteal in-stent restenosis. Therefore, we initiated a randomized controlled pilot study to prospectively determine whether PCBA, when compared with CBA, improves morphologic and clinical outcome in patients with femoropopliteal in-stent restenosis.
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MATERIALS AND METHODS
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Study Design and Inclusion and Exclusion Criteria
Consecutive patients with femoropopliteal in-stent restenosis (angiographic stenosis of >50% of the vessel lumen diameter) were enrolled from November 2004 to March 2007 in this single-center prospective randomized controlled pilot study. The protocol was approved by the institutional ethics committee and all patients provided written informed consent. Entry criteria included symptomatic peripheral artery disease with intermittent claudication or critical limb ischemia related to a recurrent stenosis in a previously stented segment of up to 20 cm in length. Only patients with a restenosis of a self-expanding nitinol stent (Absolute/Dynalink, Abbott Vascular, Abbott Park, Ill; Protégé, EV3, Paris, France; Sentinol, Boston Scientific, Galway, Ireland; or Smart Control, Cordis, Miami Lakes, Fla) implanted at our institution or others were eligible. Exclusion criteria were a history of intolerance of antiplatelet therapy, an adverse reaction to heparin, bleeding diathesis, a creatinine level of more than 2.5 mg/dL, hemodialysis, active bacterial infection, allergy to contrast media, pregnancy, and inability to give informed consent. Furthermore, patients with stent fractures were not included in the study, as treatment of fractured stents frequently requires repeat stenting of the lesion. Patients with acute stent thrombosis were also not eligible, as these patients were treated with thrombolysis prior to angioplasty.
Patient Data
Before enrollment, all patients underwent baseline testing of ankle brachial index (ABI), treadmill examinations, and duplex ultrasonography (US). Demographic data, clinical characteristics, comorbidities, current medical therapy, and time from initial stent implantation were recorded by using a standard questionnaire. Diagnostic angiography was performed before enrollment to document lesion length, degree of stenosis, and number of runoff vessels.
Interventions
Interventions were performed percutaneously by one of three experienced interventionists (M.H., E.M., and M.S., with 8, 25, and 5 years experience) from an over-the-bifurcation approach. After insertion of a 7-F sheath, 5000 IU of heparin was administered intraarterially. After successful passage of the stenosis or occlusion with the guidewire, patients were randomized to either CBA or PCBA by using computer-generated random digits and sealed envelopes. PCBA was performed by using a peripheral cutting balloon (Boston Scientific). Conventional radiographs were used to place a ruler at the patient's thigh with the distal end exactly overlapping the upper edge of the patella for standardized documentation of the lesion morphology and comparability during follow-up. We recorded the length of the target lesion in the stented segment, as well as the length of the stented segment. Degrees of stenosis were estimated visually by the interventionist. Pre- and postintervention angiograms were obtained in at least two planes (with a 30° difference). The balloon diameter in both groups corresponded to the proximal nondiseased vessel area. The number of balloon inflations was left to the discretion of the interventionist and was not recorded.
Technical success was defined as a residual stenosis of less than 30% in the worst angiographic view. Bailout stenting by using self-expanding nitinol stents was performed in patients with a residual stenosis of more than 30% or flow-limiting dissection. Patients undergoing secondary stenting were analyzed according to the intention to treat.
The duration of fluoroscopy and the amount of contrast agent were recorded.
Laboratory Data
High-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), and fibrinogen levels from venous blood samples were measured at baseline and 24 and 48 hours after the intervention. For measurement of hs-CRP values, a high-sensitivity assay (N Latex CRP Mono, DADE, Behring, Germany) was used. SAA was measured by using another assay (N Latex SAA; DADE Behring). For measurement of fibrinogen (Fibrinogen Clauss; Stago, Roche, France) was used. For hs-CRP, SAA, and fibrinogen, the respective detection levels were less than 0.03 mg/dL, less than 3.8 mg/L, and 20 mg/dL and the respective coefficients of variation were 4.6%, 6.4%, and 5.2%.
Medical Therapy
All patients received 100 mg of aspirin daily continuously, in addition to 75 mg of clopidogrel daily for 1 month after intervention. SAA and clopidogrel were initiated at least 2 days prior to the intervention, otherwise a loading dose of 300 mg of clopidogrel was given during the intervention.
Surveillance Protocol
ABI testing, treadmill exercise testing, and duplex US of the treated vessels were performed in all patients at 1, 3, and 6 months after treatment. Duplex US was performed by three experienced vascular technologists (all nonauthors with 6, 8, and 9 years of experience) who were blinded for the initial treatment strategy. A peak systolic velocity of 2.4 m/sec or more measured at duplex US was considered indicative of a 50% or higher narrowing and was defined as a recurrent restenosis (8). Reintervention at the site of the treated segment or bypass surgery was also defined as a restenosis and loss of primary patency.
Complications
Complications were classified as either major or minor. Major complications were access site complications requiring surgical interventions, bleeding complications with a decrease of serum hemoglobin of more than 2 g/dL, amputation, macroembolism with the need for further revascularization, and any death before discharge. Minor complications were those that resolved spontaneously (eg, superficial hematoma and groin pain owing to nerve injury).
Study End Points
The primary study end point was the occurrence of a greater than 50% restenosis at the treated segment at 6 months after intervention, as determined by duplex US. Secondary objectives were restenosis rates at 1 and 3 months; reintervention rates at 1, 3, and 6 months after the procedure; ABI; and walking distance at 1, 3, and 6 months after intervention. Furthermore, the course of inflammatory parameters (hs-CRP, SAA, and fibrinogen) until 48 hours after intervention was analyzed in both groups.
Statistical Analysis
Continuous data are given as the mean ± standard deviation or the median and interquartile range (from the 25th to the 75th percentile), as appropriate. Discrete data are given as counts and percentages. The Fisher exact test and Mann Whitney U test were used for between-group comparisons of baseline and follow-up data. Repeated-measures analysis of variance was applied serially to compare inflammatory parameters at baseline and at 24 hours and 48 hours between the PCBA and CBA groups. A P value of less than .05 was considered to indicate a significant difference. We used software (SPSS for Windows, version 12.0; SPSS, Chicago, Ill) for statistical analysis.
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RESULTS
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We enrolled 40 patients; one patient was lost to follow-up, leaving 39 patients for the final analysis. CBA was performed in 22 patients; PCBA was used in 17 patients. Demographic data and baseline characteristics were equally balanced between the groups (Table 1).
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Table 1. Demographics and Characteristics of 39 Patients with Symptomatic Femoropopliteal In-Stent Restenosis Randomized to PCBA or CBA
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Average length of the lesions was 80 mm ± 68. Average length of the treated segments was 85 mm ± 70 without significant difference between the two groups. Duration of fluoroscopy was slightly shorter in the CBA group. Technical success could be achieved in all patients. No major complications were observed. Bailout stenting was done infrequently in both groups (Table 2).
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Table 2. Baseline Data of 39 Patients with Symptomatic Femoropopliteal In-Stent Restenosis Randomized to PCBA or CBA
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Restenosis Rates and Outcomes
Restenosis rates in the PCBA versus the CBA group were 12% (two of 17; 95% confidence interval: 3%, 27%) versus 27% (six of 22; 95% confidence interval: 8%, 46%) at 1 month (P = .42), 47% (eight of 17; 95% confidence interval: 23%, 71%) versus 41% (nine of 22; 95% confidence interval: 20%, 62%) at 3 months (P = .75), and 65% (11 of 17; 95% confidence interval: 42%, 88%) versus 73% (16 of 22; 95% confidence interval: 54%, 92%) at 6 months (P = .73) (Fig 1).
Clinically, comparable outcomes between PCBA and CBA were observed until 6 months after intervention. ABI (0.83 vs 0.75, P = .26) and maximum walking capacity on the treadmill (117 m vs 103 m, P = .97) at 6 months were not significantly different between the two groups (Fig 2); other clinical outcomes, including reintervention rates, were also nearly identical (Table 3).
Laboratory Parameters
Laboratory parameters of inflammation showed a comparable increase from a baseline hs-CRP level of 0.15 mg/dL ± 0.11 to 0.51 mg/dL ± 0.78 at 24 hours after intervention and to 0.97 mg/dL ± 1.4 at 48 hours after intervention in the PCBA group versus a baseline level of 0.35 mg/dL ± 0.24 to 0.67 mg/dL ± 0.78 at 24 hours after intervention and to 1.04 mg/dL ± 1.23 at 48 hours after intervention in the CBA group (P = .43 by repeated-measures analysis of variance). Comparable results were obtained for SAA and fibrinogen. Respective SAA levels at baseline and 24 and 48 hours after intervention were 6.5 mg/L ± 1, 17 mg/L ± 6, and 22 mg/L ± 7 in the PCBA group versus 8.2 mg/L ± 2, 16 mg/L ± 8, and 28 mg/L ± 7 in the CBA group (P = .38). Respective fibrinogen levels at baseline and 24 and 48 hours after intervention were 358 mg/dL ± 36, 395 mg/dL ± 30, and 415 mg/dL ± 39 in the PCBA group versus 380 mg/dL ± 28, 401 mg/dL ± 38, and 423 mg/dL ± 41 in the CBA group (P = .31).
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DISCUSSION
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In our pilot study, we observed no substantial benefit of PCBA compared with CBA for treatment of symptomatic femoropopliteal in-stent restenosis. Restenosis rates in both treatment groups were disappointingly high, clinical outcomes were closely comparable, and the postintervention course of inflammatory parameters was not different in favor of PCBA. Although these are pilot data, they raise the question of whether or not PCBA should be advocated routinely for treatment of femoropopliteal in-stent restenosis in lesions with an average length of 8 cm.
Restenosis rates in both groups were excessively high, underlining that endovascular treatment of in-stent restenosis remains an urgent clinical concern. Notably, clinical deterioration rarely occurred. Nevertheless, reinterventions were performed rather liberally in both groups, even in patients with recurrence of only mild symptoms. The rationale for these "service interventions" is that in long stents, even focal restenosis can be easily redilated, but left untreated, may lead to long-segment stent thrombosis. Endovascular revascularization of stent thrombosis bears a considerable risk of peripheral embolization.
In coronary arteries, the cutting balloon has been evaluated in de novo lesions, as well as for the treatment of in-stent restenosis (9–12). These studies unequivocally demonstrated the safety of the device; however, a large meta-analysis of randomized trials failed to prove superiority compared with CBA (12). PCBA therefore is currently only considered as a niche indication, mainly for plaque preparation prior to coronary stenting.
The peripheral cutting balloon device was introduced several years ago. Nevertheless, only minimal data systematically evaluating its performance have been reported (5,6,13); to date, and to our knowledge, no randomized studies exist. Previous reports suggested a reduced rate of angiographically visible dissection for infrainguinal applications (14). Furthermore, given the findings in coronary arteries, a reduction of vascular inflammation after PCBA compared with CBA (7) was anticipated, and thus, there was a beneficial effect on femoropopliteal restenosis (15). Disappointingly, this concept could not be proved in our study, neither with respect to inflammatory parameters nor regarding morphologic and clinical outcomes. It remains debatable whether inflammation is a relevant player in the development of in-stent re-restenosis.
Still, there seems to be a place for PCBA in femoropopliteal arteries, mainly for treatment of a rigid or heavily calcified stenosis when inflation of conventional or high-pressure balloons remains inadequate to prepare a lesion for stenting. Particularly in the era of nitinol stents, which provide only limited radial force, adequate dilation before stent implantation can be crucial and PCBA certainly is of help in selected cases.
Our study had limitations. The small sample size of this study did not allow drawing any final conclusions on PCBA for treatment of in-stent restenosis. In particular, since we included lesions up to 20 cm in length, we cannot exclude that PCBA may exert beneficial effects in more focal lesions. Nevertheless, the excessively high rate of restenosis, even at 3 and 6 months after intervention in the PCBA group, indicates that this technology certainly is not a major solution in the treatment of patients with extensive in-stent restenosis, such as those included in our study.
In conclusion, PCBA failed to prove superior to CBA for treatment of femoropopliteal in-stent restenosis in our randomized pilot study. In restenotic lesions with an average length of approximately 8 cm, both treatment methods yielded disappointing 6-month patency rates.
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ADVANCE IN KNOWLEDGE
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- In our pilot study, cutting balloon angioplasty does not improve morphologic or clinical patency as compared with conventional balloon angioplasty in patients treated for femoropopliteal in-stent restenosis.
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IMPLICATION FOR PATIENT CARE
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- Although data are preliminary, we suggest that cutting balloon angioplasty cannot be routinely recommended for treatment of femoropopliteal in-stent restenosis of a mean lesion length of approximately 8 cm.
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FOOTNOTES
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Abbreviations: ABI = ankle brachial index • CBA = conventional balloon angioplasty • hs-CRP = high-sensitivity C-reactive protein • PCBA = peripheral cutting balloon angioplasty • SAA = serum amyloid A
Author contributions: Guarantors of integrity of entire study, E.M., M.S.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, all authors; clinical studies, all authors; statistical analysis, P.D., M.S.; and manuscript editing, all authors
Authors stated no financial relationship to disclose.
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References
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- Schillinger M, Sabeti S, Dick P, et al. Sustained benefit at 2 years of primary femoropopliteal stenting compared to balloon angioplasty with optional stenting. Circulation 2007;115:2745–2749.[Abstract/Free Full Text]
- Duda SH, Bosiers M, Lammer J, et al. Drug-eluting and bare nitinol stents for the treatment of atherosclerotic lesions in the superficial femoral artery: long-term results from the SIROCCO trial. J Endovasc Ther 2006;13:701–710.[CrossRef][Medline]
- Schlager O, Dick P, Sabeti S, et al. Stenting of the superficial femoral artery: the dark sides—restenosis, clinical deterioration and fractures. J Endovasc Ther 2005;12:676–684.[CrossRef][Medline]
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ABSTRACT
INTRODUCTION
