By Bosiers, M Deloose, K; Verbist, J; Peeters, P
Aim. We investigated the efficacy of Xpert (Abbott Vascular Devices) nitinol stents for the treatment of infrapopliteal lesions In patients with critical limb ischemia (CLI). Methods. Between May and October 2005,47 CLI patients (35 men, mean age 73 years) received 67 Xpert stents for the treatment of 58 infrapopliteal lesions in 51 limbs; 43 patients (84.3%) were classified in Rutherford Category 4 and 8 (15.7%) in Category 5. Clinical examination and quantitative vascular analysis (QVA) were performed before and after the intervention and at 12-months follow-up. The primary endpoint was defined as 1-year angiographic binary restenosis rate (>50% stenosis on QVA); the secondary endpoints were 1-year primary patency and limb salvage rate.
Results. QVA after 1 year showed a binary restenosis rate of 20.45%. Kaplan-Meier analysis revealed 1-year primary patency and limb salvage rates of 76.3% and 95.9%, respectively. The limb salvage rate was significantly better in patients with proximal below-the-knee (BTK) than in those with mid-section or distal lesions (100% vs 81.8%; P-0.0071).
Conclusion. Our results suggest that treatment with nitinol Xpert stents in CLI patients is effective and yields satisfactory angiographic and clinical outcome.
KEY WORDS: Limb ischemia – Nitinol – Stents – Peripheral arterial disease – Limb salvage.
Percutaneous transluminal angioplasty (PTA) is the current standard endovascular method of treatment in patients presenting with critical limb ischemia (CLI) due to below-the-knee (BTK) lesions.1 Because of the paucity of data on stent use in the infragenicular arterial bed, stent placement in this patient cohort is generally done only after suboptimal PTA results, namely flow- limiting dissections or residual stenosis of at least 50% after balloon dilation.
As coronary and below-the-knee arteries have similar diameters, balloon-expandable coronary type stents were initially proposed for placement in the belowknee segment. However, the crushability of balloonexpandable stents entails potential stent complications, particularly when used in these superficial and often very calcified arteries. Moreover, application of this stent type is difficult in tortuous anatomy. The use of non-crushable, highly adaptable self- expanding nitinol stents overcomes this problem and could potentially improve long-term stent outcome, analogous to the results of various SFA trials.2″4 In this respect, nitinol stents are indicated for improving long-term results after BTK implantation. However, most cunently available nitinol stents have a vessel-to-wall ratio that is too high to avert intimal hyperproliferation after implantation. With the recent introduction of the Xpert stent (Abbot Vascular Devices), the first small- diameter nitinol stent with a low vessel-to-wall ratio, specifically designed for BTK usage, has become available.
The primary objective of this single-centre, prospective controlled study was to assess the mid-term efficacy of the Xpert nitinol stent in the treatment of patients with CLI.
Table I.-Inclusion and exclusion criteria.
Materials and methods
This prospective controlled study was approved by the Ethics Committee of our hospital. An overview of inclusion and exclusion criteria is given in Table I. Between May and December 2005, 51 limbs were treated in 47 CLI patients (35 men, mean age 73 years); 58 lesions were treated with 67 Xpert stents; 43 (84.3%) limbs were classified as Rutherford 4 and 8 (15.7%) as Rutherford 5. Six (12.8%) patients were ASA class 2, 22 (46.8%) ASA class 3 and 19 (40.4%) ASA class 4. A history of tobacco use was noted in 23 (48.9%) patients, co-morbidities were arterial hypertension in 32 (68.0%), hypercholesterolemia in 32 (68.0%) and diabetes in 19 (40.4%) patients.
Device
The study device was the Xpert Self-Expanding Stent System (Abbott Vascular, Redwood City, CA, USA). Nitinol stents are available in diameters from 3 to 8 mm and lengths from 20 up to 80 mm. The 4-F introducer sheath compatible nitinol stent system is specifically designed for small vessel application. Once implanted, the stent offers good flexibility and low straightening force that ensures wall apposition and delivers radial force equivalent to that of competitive 5F and 6-F systems. The system is 0.018″-wire compatible and comes in 90 cm and 135 cm catheter lengths.
Follow-up visits
Follow-up control visits were scheduled 6 and 12 months postoperatively. At each visit, clinical assessment was performed by Duplex examination and Rutherford categorization. At 1-year follow- up, an additional angiographic control was performed.
QVA measurements on pre and postprocedural and 1-year angiographic images (Figure 1) were performed using on-site X-ray analysis software (Advantage Workstation 4.2, General Electric Medical Systems). At 1-year assessment, late lumen loss (LLL) and LLL index were calculated. The LLL is defined as the difference between the minimum lumen diameter (MLD) after 1 year and the postoperative MLD. The LLL index is defined as the ratio between the LLL and the postoperative reference vessel diameter (RVD).
Endpoints
The primary endpoint of the study was loss of angiographic patency after 1 year, defined as binary restenosis rate at the stented artery site. The secondary endpoints were 1-year limb salvage (absence of major amputation) and absence of reintervention. Serious adverse events, defined as death, amputation and the need for revascularization, were recorded according to standard classifications.
Anticoagulation regimen
Daily aspirin therapy was initiated and clopidogrel saturation (75 mg daily for at least 4 days or 1 loading dose of 300 mg the day before the procedure) was obtained prior to the procedure. Heparin was used during the procedure (bolus of 150 IU/kg body weight). The postprocedure antithrombotic regimen was that used according to the routine clinical practice of the hospital (clopidogrel 75 mg daily for 1 month – aspirin 100 mg daily lifelong – 0.6 fraxiparin daily for 3 weeks).
Figure 1.-QVA-analysis of patient treated with 6×60 Xpert nitinol stent for a total occlusion of the tibiofibular trunk (TFT). A) Preprocedural image showing total occlusion of the TFT; B) location of stent implantation; C) immediate postoperative image showing
Statistical analysis
Statistical analysis of the follow-up data of the entire patient group was done by using Kaplan-Meier estimates. The analyses were further stratified by lesion location: lesions in the proximal part of the crural vessels were compared to those in the mid and distal segments. All calculations were performed using MedCalc statistical software (version 9-2.0.1).
Results
Contralateral access is preferred for BTK endovascular procedures in our vascular surgery department and was performed in 90.2% (46) of cases. The mean operating time was 56 minutes (range 20-110). A mean of 118 mL (range 50-250) contrast dosage was injected, with a mean fluoroscopy time of 13 minutes (range 2-37).
The mean RVD was 2.9 mm (range 1.6-4.0). Calcification, dissection or ulceration at the lesion site was found in 17 (29.3%), 2 (3.4%) and 1 (1.7%), respectively. Of the 58 lesions treated, 47 BTK lesions were in the proximal portion of the crural arteries and 11 in the mid or distal section. The mean preoperative degree of stenosis was 92.7% (range 60-100). In total, 31 (53.4%) occlusions and 27 (46.6%) stenoses were treated. The mean lesion length was 32.4 mm (range 6-100). Lesion location distribution over the popliteal artery (P3), tibiofibular trunk, anterior tibial artery, peroneal artery and posterior tibial artery was 7 (12.0%), 10 (17.3%), 17 (29.3%), 13 (22.4%) and 11 (19.0%), respectively.
Table II.-Overview of Xpert stent sizes.
Stent implantation was successful in all 51 procedures. In total, 67 Xpert nitinol stents (mean diameter 4.6 mm [range 3-0-6.0] and length 39-6 mm [range 2060]) were implanted. An overview of the different stent sizes is given in Table II.
Table III.-Results of quantitative vascular analysis.
Figure 2.-Kaplan-Meier estimate of survival.
Figure 3.-Kaplan-Meier estimate of primary patency.
After 1 year, QVA data could be collected for 44/58 (76%) lesions in 37/51 (73%) procedures (Table III). The mean MLD was 0.25 mm (preprocedure), 2.71 mm (postprocedure) and 1.89 mm (at 1-year control angiography), corresponding to a mean stenosis rate of 91.65% (preprocedure), 5.69% (postprocedure) and 27.47% (at 1-year control angiography). At 1 year after the index intervention, the mean LLL was 0.81 mm, corresponding to a LLL index of 30%. The 1- year binary restenosis rate was 20.45%.
Kaplan-Meier estimate showed a 1-year survival rate of 81.2% (Figure 2): 6 patients died because of myocardial infarction, 1 because of pneumonia and 1 following sigmoid perforation after colonoscopy. One-year primary patency and limb salvage rates were 76.3% and 95.9%, respectively, according to Kaplan-Meier estimates (Figure 3, 4). Stratification by lesion location (Figure 5, 6) revealed a tendency towards better 1-year primary patency rates in the CLI patients with proximal BTK lesions than in those with mid section or distal BTK lesions (85.1% vs 48.5%; P=0.0554). The 1- year limb salvage rates were significantly better in the former group (100% 1*81.8%; P-0.0071). Discussion
Concern about the substantial consequences of CLI in general and in patients in particular is warranted. As the population ages and the diabetes epidemic continues to spread,5 a steep climb in the number of CLI patients is expected, for many of whom amputation is the only treatment proposed.6.7 Less than half of all amputees achieve mobility, resulting in a low quality of life and a huge economic burden of the treatment on society.7
Figure 4.-Kaplan-Meier estimate of limb salvage.
Figure 5.-Kaplan-Meier estimate of primary patency stratified by lesion location.
According to a meta-analysis by Albers et al., popliteal-to- distal venous bypass placement in CLI patients results in 1-year primary patency and limb salvage rates up to 80% and 90%, respectively.8 In our patient cohort, the 1-year clinical outcome after nitinol Xpert stenting BTK was 76.3% for primary patency and 95.9% for limb salvage, both of which are in line with published surgical data. Our promising results suggest and further support the growing acceptance that endovascular treatment of BTK lesions will become the primary treatment strategy for CLI patients in the near future. Corroborating this scenario are studies9-14 that have listed factors contributing to the growing importance of endovascular therapy in this challenging patient subset: new hopes for those patients unfit for surgical bypass placement (due to either co- morbidities or inadequate conduit or absence of distal target vessels); advantage of local over general anesthesia; reduced hospitalization time and potential reduction in the cost of treatment.
Figure 6.-Kaplan-Meier estimate of limb salvage stratified by lesion location.
The BASIL trial participants14 played a pivotal role in this shift towards an endovascular approach for patients with CLI due to infrainguinal disease. They were the first to publish the findings from a controlled, randomized study that compared the results of bypass surgery and those of PTA in CLI patients: both treatments yielded similar outcomes, with angioplasty being the less expensive alternative.
To date, expected patency rates for infrapopliteal angioplasty lie between 40% and 78% at 2 years.15, 16 Similarly, a meta regression analysis has also shown limb salvage rates of 79% at 1 year and 74% at 2 years.17 The current general belief is that the endovascular approach should be limited to balloon angioplasty and that BTK stenting should be avoided. There is general consensus for additional stent implantation only when an immediate suboptimal angiographic outcome after PTA is observed (i.e. flow-limiting dissection or significant residual stenosis). The drawback to BTK stenting is that the small vessel diameter leads to potential early restenosis or occlusion due to neointima hyperplasia.
Nevertheless, we believe that this reluctance to apply stents in the BTK area may be abandoned soon, given the significantly better 6- month angiographic outcome of passive coated stenting versus PTA in the randomized controlled trial by Rand et al.18 and the low 1-year angiographic binary restenosis rate of 20.45% in our patients after nitinol stenting.
Four recent independent studies1922 reported favorable stent outcome after implantation of balloonexpandable sirolimus-eluting- stents (SES), with high mid-term primary patency and limb salvages rates. Despite these good outcomes, currently commercially available SES are all balloon-expandable, which makes them prone to stent fracture, as recently documented by Schwarzmaier-D’Assie et al.23 Keeping in mind the findings in the superficial femoral artery, where Scheinert et al.24 found a direct link betw`een stent fracture and lesion reocclusion, the fractureprone nature of balloon- expandable 316-L stainless steel stents could potentially lead to less encouraging long-term outcomes of SES and other balloon- expandable stent types.
The remarkable long-term clinical and marked improvement in angiographic LLL after placement of self-expanding nitinol Xpert stents in infrapopliteal vessels may be explained by the crush- resistant, highly flexible features of nitinol. Moreover, thanks to its reduced strut profile, the Xpert stent design intends to improve results by lowering wall coverage up to 20%, independently of stent diameter. The rationale is that optimal maintenance of flow dynamics in the infrapopliteal arteries lowers lumen loss and improves patency rates.
Despite the differences between infrapopliteal and coronary vascular beds, the application of nitinol for infrapopliteal stenting results in a long-term angiographic outcome comparable to that of bare-metal stents in coronary arteries, as seen in major metaanalyses of coronary trials.2527 The findings of this investigation were beyond expectation and are very promising for future stent development. Combining nitinol stent technology with active drug coatings could lead to even better clinical and angiographic outcomes, as seen in coronaries,25-27 which opens new prospects for future CLI strategies.
Limitations of the study
The single-centre, non-randomized design of this prospective controlled study warrants careful interpretation of the results, and the small study population (N=47) might have caused a potential bias. Therefore, a large-scale randomized trial comparing nitinol stenting BTK versus either PTA or balloon-expandable stent implantation would be recommendable to validate these findings.
Another limitation of our study is that, because the smallest diameter stents were unavailable at the start of the trial, there was a tendency towards oversizing the vessels, thus potentially negatively influencing flow dynamics.
Conclusions
In this series of patient with CLI, application of the dedicated nitinol Xpert stent in BTK lesions led to remarkable long-term clinical and angiographic outcomes. QVA after 1 year showed a binary restenosis rate of only 20.45%, which is comparable to wellaccepted restenosis rates in coronary trials. KaplanMeier estimates showed 1- year primary patency rates of 76.3% and limb salvage rates of 95.9%. These findings suggest that implantation of nitinol Xpert stents for treating BTK lesions in CLI patients might change the perspective of infrapopliteal endovascular strategies in favour of stent use.
Acknowledgements.-The authors take great pleasure in thanking the staff of Flanders Medical Research Program (www.fmrp.be), especially Koen De Meester and Erwin Vinck for performing the systematic review of the literature and providing substantial support to the data analysis and the writing of the article.
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M. BOSIERS 1, K. DELOOSE 1, J. VERBIST 2, R PEETERS 2
1 Department of Vascular Surgery
AZ St-Blasius, Dendermonde, Belgium
department of Cardiovascular And Thoracic
Imelda Hospital, Bonheiden, Belgium
Address reprint requests to: M. Bosiers, Department of Vascular Surgery, AZ St-Blasius, Kroonveldlaan 50, 9200 Dendermonde, Belgium. E-mail: [email protected]
Copyright Edizioni Minerva Medica Aug 2007
(c) 2007 Journal of Cardiovascular Surgery. Provided by ProQuest Information and Learning. All rights Reserved.
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