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Vascular and Interventional Radiology |
1 From the Department of Angiology, University of Vienna Medical School, Waehringer Guertel 18–20, A-1090 Vienna, Austria. Received August 22, 2003; revision requested November 4; revision received November 20; accepted January 12, 2004. Address correspondence to S.S. (e-mail: schila.sabeti@akh-wien.ac.at).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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MATERIALS AND METHODS: The authors analyzed the clinical and imaging data of 175 consecutive patients with peripheral artery disease and either intermittent claudication (n = 150) or critical limb ischemia (n = 25) who underwent femoropopliteal artery implantation of nitinol (n = 104) or stainless steel (n = 123) stents in a nonrandomized setting. The stents were placed owing to either significant residual stenosis (ie, >30% lumen diameter reduction) or flow-limiting dissection after initial balloon angioplasty of the femoropopliteal artery. Patients were followed up for a median period of 9 months (mean, 13 months; range, 6–66 months) for the detection of a first in-stent restenosis, defined as a greater than 50% lumen diameter reduction that was seen at color-coded duplex ultrasonography and confirmed at angiography.
RESULTS: Cumulative patency rates at 6, 12, and 24 months were 85%, 75%, and 69%, respectively, after nitinol stent placement versus 78%, 54%, and 34%, respectively, after stainless steel stent placement (P = .008, log-rank test). There were no statistically significant differences in associated patency among the three different nitinol stents used (P = .72, log-rank test). Multivariate Cox proportional hazard analysis, in which the effect of propensity to receive a nitinol stent was considered, revealed a significantly reduced risk of restenosis with the nitinol stents compared with the risk of restenosis with the stainless steel stents (adjusted hazard ratio, 0.44; 95% confidence interval: 0.22, 0.85; P = .014).
CONCLUSION: Nitinol stents are associated with significantly improved primary patency rates in femoropopliteal arteries compared with stainless steel stents. Randomized controlled trials are needed to confirm these results.
© RSNA, 2004
Index terms: Arteries, extremities • Arteries, restenosis, 92.721 • Arteries, stenosis or obstruction, 92.721 • Arteries, transluminal angioplasty, 92.1281, 92.1282, 92.1286 • Stents and prostheses, 92.1268, 92.1286
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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Recently, the use of nitinol devices has seemed to improve the durability of femoropopliteal stents: 3-year patency rates of up to 76% have been reported (6,7). These promising results led us to hypothesize that nitinol stents are associated with improved primary patency in femoropopliteal arteries compared with stainless steel stents. Therefore, the aim of the present study was to evaluate, in a propensity score–adjusted analysis, the intermediate-term primary patency rates associated with nitinol versus stainless steel self-expanding stent placement for the treatment of atherosclerotic lesions in femoropopliteal arteries.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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Patients with lower limb ischemia that was categorized as severe intermittent claudication (Fontaine stage IIb, which corresponds to Rutherford stage III) or with critical limb ischemia (Fontaine stages III or IV, which correspond to Rutherford stages IV–VI) were eligible to undergo endovascular revascularization procedures during the study period. Elective stent implantation in the femoropopliteal arteries was performed only in cases of primary PTA failure due to a residual stenosis of greater than 30% or to flow-limiting dissection at the initially dilated segment. Stent implantation was not performed in the middle and distal thirds of the popliteal artery. The choice of using a nitinol stent or a stainless steel stent was left to the discretion of the interventionist. Thirty-six patients who underwent endovascular brachytherapy after stent implantation as part of a concurrent study protocol were excluded from this analysis.
Definitions
In all patients, the diagnosis of peripheral artery disease was determined by using clinical evaluation, ankle-brachial index (ABI) measurements, and duplex ultrasonography (US) and was confirmed at lower limb angiography. Lesions causing a diameter reduction of at least 50% at visual inspection were considered to be hemodynamically relevant. Primary technical success after stent implantation was defined as a remaining diameter reduction of less than 30% at visual inspection and the absence of flow-limiting dissection at the stent-treated segment on the final angiogram. Flow-limiting dissection was defined on the basis of (a) a persistent diameter reduction of greater than 30% at visual determination or (b) slow contrast material runoff similar to TIMI (thrombolysis in myocardial infarction) I or TIMI II flow in the coronary circulation. Pressure gradient measurements were not obtained in the femoropopliteal arteries because, to our knowledge, they have never been proved to be useful.
Inflow disease was defined as greater than 50% stenosis in the iliac or common femoral arteries proximal to the superficial femoral artery. In all patients, inflow disease was evaluated at color-coded duplex US prior to a scheduled intervention, and concomitant lesions in these arteries were treated simultaneously during either a crossover intervention or a separate procedure before the superficial femoral artery intervention. Poor runoff was defined as occlusion or significant stenosis of at least two tibioperoneal arteries (ie, arteries distal to the crural trifurcation). Restenosis was defined as a greater than 50% diameter reduction in the segment, including the stent-treated segment and the interface between the stent-treated segment and the adjacent artery (edge stenosis), as measured by using manual calipers. Primary patency was defined as absence of restenosis.
Patients
During the study period, 195 (16%) of 1,192 patients who had undergone superficial femoral artery interventions underwent stent implantation after primary PTA failure. Of these 195 patients, 20 (10%)—12 men with a median age of 72 years (interquartile range [IQR] from the 25th to the 75th percentile, 63–77 years) and eight women with a median age of 77 years (IQR, 70–79 years; P = .34)—who were lost to follow-up had to be excluded. Fourteen (70%) of these 20 patients received a stainless steel stent, and six (30%) received a nitinol stent. There were no significant differences in demographic data, clinical characteristics, or lesion morphology (data not shown) between these 20 patients and the 175 patients with follow-up data who formed the study group (
2 and Mann-Whitney U tests). We included the 175 (90%) patients (median age, 70 years; IQR, 60–75 years; total age range, 42–99 years) who had follow-up data in the final analysis. Of these 175 patients, 101 (58%) were men (median age, 65 years; IQR, 57–72 years) and 74 (42%) were women (median age, 72 years; IQR, 63–78 years; P < .001).
Interventions
Two interventionists (E.M., R.A.) with more than 15 years of experience performed all of the interventional procedures by following a standard protocol. Patients received 5,000 IU of heparin intraarterially after placement of the arterial sheath. We recorded the dose of nonionic low-osmolality contrast agent (ioversol, Optiray 320; Mallinckrodt, St Louis, Mo) administered. The location, degree, and length of the stenosis or occlusion were documented. The balloon diameter for subsequent angioplasty corresponded to the diameter of the proximal nondiseased vessel. Stent implantation was performed in the cases of an insufficient primary PTA result—specifically, those of a residual stenosis of at least 30% or of a flow-limiting dissection at the initially dilated segment. The technical results of stent implantation in terms of initial technical success, postprocedural residual stenosis, and number of runoff vessels were determined on the basis of findings on the final angiograms.
For the stent implantations performed during the study period, only self-expandable stents with a nominal diameter of 6 mm were used. A first-generation stainless steel stent (Easy Wallstent; Boston Scientific, Baltimore, Md) or one of three nitinol stents (Smart Stent, Cordis, Miami, Fla; Dynalink Stent, Guidant, Santa Clara, Calif; Expander Stent, Bolton Medical, Nancy, France) was placed. These stents are approved by the relevant authority in our country for use in femoropopliteal segments. If more than one stent was implanted, only one brand was used per patient. During the study period, there were no guidelines or recommendations at our institution as to which stent to use.
Medical technicians, with supervision from one of the authors (E.M.), performed color-coded duplex US and ABI measurements 24 hours after PTA to document technical success or the presence of early restenosis. Peri- and postintervention complications at the site of the arterial puncture and/or at the stent-treated vessel segment were documented up to 48 hours after the intervention. All patients took antithrombotic medication—specifically, 75 mg of clopidogrel daily, starting with a loading dose of 300 mg immediately after stent implantation, and 100 mg of acetylsalicylic acid—for at least 4 weeks after the intervention. They usually continued to take acetylsalicylic acid thereafter.
Color Duplex US
At all baseline and follow-up US examinations, medical technicians, with supervision from one of the authors (E.M.), visualized the entire femoropopliteal segment, from the femoral bifurcation to the origin of the anterior tibial artery, by using a 5-MHz linear-array color probe (model XP 10; Acuson, Mountain View, Calif). The exact location and extent of the target lesion were determined at baseline US evaluation by determining the distance from the femoral bifurcation to the proximal point of the lumen diameter reduction. The length of the target lesion was then measured and illustrated in a graph. The peak systolic velocity in the target lesion was determined and compared with the peak systolic velocity in the preceding normal segment. A focal increase in the peak systolic velocity of at least 140% (corresponding to a peak velocity ratio of 
2.4) was considered to be indicative of a stenosis of greater than 50% at that site (9).
Follow-up to Detect Restenosis
Patients were reexamined in the outpatient clinic 3, 6, and 12 months after PTA and annually thereafter for the possible detection of restenosis. However, the patients were also advised to immediately visit the outpatient clinic at the onset of new or worsening symptoms. Evaluations of patient complaints, physical reexaminations, and ABI measurements were performed for assessment of possible restenosis. Patients suspected of having restenoses, as indicated by a 0.15 decrease in ABI, underwent duplex US. In the cases of US-based suspicion of restenosis, follow-up angiograms were obtained by the same interventionists (E.M., R.A.). Overall, 143 (82%) patients underwent duplex US and 97 (55%) underwent follow-up angiography to confirm the findings of duplex US. All patients who were found to have a restenosis underwent follow-up angiography. Two independent observers (S.S., J.A.) who were blinded with regard to the baseline patient data and the kind of stent implanted evaluated the follow-up data in consensus.
Statistical Analyses
Continuous data are presented as median values and IQRs or as means and total ranges. Discrete data are given as counts and percentages. 2 tests or, where appropriate, exact tests were performed to compare groups of categorical data and to test for trends. The Mann-Whitney U test was used to compare continuous data. Primary patency rates were compared between the nitinol stent and stainless steel stent groups by using the log-rank test and are presented as Kaplan-Meier curves. Multivariate Cox proportional hazards models were applied to assess the effect of nitinol stent versus stainless steel stent implantation on primary patency, with the effect of the stent implant choice adjusted to include the propensity to receive a nitinol stent (8). The following baseline clinical characteristics were entered into a multivariate logistic regression model to derive a propensity score: age, sex, body mass index, diabetes, critical limb ischemia, recurrent stenosis after PTA, lesion length, vessel runoff, complete vessel occlusion, and concomitant statin therapy. Furthermore, the date of stent implantation was included to account for temporal trends in the use of nitinol stents during the study period.
The study population was then divided into quartiles according to propensity score, with the balancing property satisfied. Within each quartile, the patients who had nitinol stent implants were compared with those who had stainless steel stent implants. We then entered the propensity score, along with other, potentially confounding variables, into the Cox proportional hazards model as a continuous variable to examine the adjusted effects of nitinol stent implantation on restenosis.
Variables that were imbalanced between the two stent groups (ie, patients with nitinol stents and patients with stainless steel stents), as well as between the patients with and those without restenoses (as indicated by P < .20), were entered into the Cox model as potentially confounding variables. We tested for interactions between the baseline variables by using multiplicative interaction terms and log likelihood 2 tests. The results of the Cox proportional hazards model are presented as hazard ratios and 95% confidence intervals. A two-sided P value of less than .05 was considered to indicate statistical significance. One of the authors (M.S.) performed statistical calculations by using computer software (Stata, release 8.0, and SPSS for Windows, version 10.0; SPSS, Chicago, Ill).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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In the propensity score–adjusted model (derived at multivariate logistic regression analysis), the following factors, although not significant at the 5% level, were associated with nitinol stent use (in descending order): later date of stent implantation during the study period (P = .062), absence of diabetes (P = .064), and complete vessel occlusion (P = .086).
Follow-up to Detect Restenosis
During the median follow-up period of 9 months (mean, 13 months; range, 6–66 months), 87 (50%) patients developed restenoses, which included in-stent restenoses and edge stenoses. Patients in the nitinol stent group had significantly better primary patency rates than did patients in the stainless steel stent group (Figure). Cumulative primary patency rates at 6, 12, and 24 months after nitinol stent placement were 85%, 75%, and 69%, respectively, versus 78%, 54%, and 34%, respectively, after stainless steel stent placement (P = .008, log-rank test). There were no significant differences in associated primary patency rates among the three brands of nitinol stents used (P = .72, log rank test). Male sex, greater degree of stenosis, and complete vessel occlusion were other factors associated with restenosis (Table 2). The indication for stent placement—that is, residual stenosis or flow-limiting dissection—was not significantly associated with restenosis (Table 2).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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It has been demonstrated that the implantation of stainless steel stents in femoropopliteal arteries does not improve the postangioplasty outcome of the treated segments (2–5). Therefore, stent placement in this vessel area is still considered a bail-out procedure that is performed to salvage the initial failure of balloon dilation. However, the early findings of Henry et al (1) and the recent data published from different groups (6,7) suggest that improved patency rates may be achieved by using nitinol stents. Duda and colleagues (6) reported a restenosis rate of only 23.5% within 6 months after implantation of noncoated nitinol stents in the superficial femoral artery, and Lugmayr et al (7) reported a 3-year primary patency rate of 76% after nitinol stent implantation in complex superficial femoral and popliteal artery lesions. Similarly, the use of self-expandable nitinol stents in the coronary circulation has been shown to have promising results, even in vessels that are associated with high restenosis rates, such as saphenous vein grafts (14). In addition to the unique mechanical properties of nitinol, reduced thrombogenicity of the nitinol surface may contribute to the reduction of in-stent neointimal proliferation (15).
The promising patency rates observed with nitinol stent placement in the current study, even in patients who had long lesions and/or occluded vessels, suggest that the primary placement of nitinol stents might be more effective than performing conventional balloon angioplasty. This issue has to be addressed in a randomized controlled trial. Performing primary stent placement—that is, recanalization of the obstructed segment with a guidewire, passage with the self-expanding low-profile stent, expansion of the stent, and balloon dilation strictly within the boundaries of the stent—might further increase patency rates compared with performing secondary stent placement, as was done in the present study.
It is known from animal experiment results that primary stent placement leads to reduced vessel wall trauma and consequently to neointima formation (16). Nevertheless, the current study findings favor the use of nitinol stents, at least in patients with suboptimal angiographic results after balloon dilation. Other measures that have been used successfully to improve the patency rates of endovascular treatment of the femoropopliteal arteries include endovascular brachytherapy (17,18) and the soon-to-be-available drug-eluting stents (6). The question of which of these techniques will succeed in terms of the optimal cost-benefit ratio will be answered in the near future.
Some variables that are established risk factors for restenosis, such as lesion length, stent-treated segment length, and vessel runoff, were not associated with restenosis in the present study. We can only speculate about the causes for this lack of association (presumably a type II error), which remains unclear. Furthermore, the prevalence of diabetes mellitus was imbalanced between the nitinol stent and stainless steel stent groups. Although we adjusted for these imbalances by using a propensity score and adding the variable of diabetes to the Cox proportional hazards model, diabetes still may be a relevant confounding variable, particularly since reduced patency rates for diabetic patients who receive nitinol stents have also been reported (7).
We did not include the subgroup of patients, out of the total of 1,192 patients, who were treated with balloon angioplasty during the study period because a comparison between PTA and stent placement in this context would have been flawed owing to the fact that the patients were negatively selected for the stent placement procedure. Further trials are necessary to determine whether nitinol stent placement is superior to balloon angioplasty in terms of effectiveness.
As is inherent to any observational study, the assignment of patients to the nitinol stent and stainless steel stent groups was not randomized. Despite the use of contemporary statistical methods to adjust for the kind of stent implanted, nonmeasured confounding variables may have affected the decision of whether to implant a nitinol stent or a stainless steel stent and the rates of restenosis observed during follow-up. In particular, there may have been other variables besides the stent that improved during the 5-year study period and thus that may have influenced our findings. However, lesion morphology, indications for stent placement, and pre- and postintervention ABI values were similar between the two stent groups. To further account for any temporal trends, we included the date of stent implantation both in the calculations of the propensity score and in the fully adjusted Cox proportional hazards model. Thus, with adjustment for the date of stent implantation during the study period, nitinol stents seemed to perform better than stainless steel stents in terms of associated restenosis.
We acknowledge that we compared a population of patients who received one type of stainless steel stent (Wallstent) with a group of patients who received either of three types of nitinol stents (Smart, Dynalink, and Expander stents). When we compared the associated restenosis rates among the three nitinol stents used, we observed no significant differences. Nevertheless, a type II error due to the small sample size—particularly in the group of patients who received Expander stents—cannot be entirely excluded.
We did not assess the minimal lumen diameter after stent placement or the relationship between this measurement and restenosis in the two treatment groups. However, measuring the ABI before and after the intervention may have been an acceptable surrogate method of comparing hemodynamic characteristics between the nitinol and stainless steel stent groups.
In conclusion, nitinol stent placement resulted in significantly improved primary patency in the femoropopliteal arteries compared with the primary patency that resulted from stainless steel stent placement. However, we believe randomized controlled trials are warranted to confirm these results because the effects of confounding factors such as diabetes mellitus cannot be ruled out with certainty in a retrospective study.
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FOOTNOTES |
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Author contributions: Guarantors of integrity of entire study, E.M., S.S., M.S.; study concepts, S.S., M.S., C.S., J.A., W.M.; study design, S.S., M.S., R.A., E.M.; literature research, S.S., E.M., M.S.; clinical studies, E.M., R.A.; data acquisition, S.S., J.A., C.S.; data analysis/interpretation, S.S., M.S., W.M., E.M., R.A.; statistical analysis, M.S.; manuscript preparation, S.S., M.S.; manuscript definition of intellectual content, revision/review, and final version approval, all authors; manuscript editing, M.S., S.S.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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