Percutaneous Angioplasty With and Without Stenting for Lower Extremity Occlusive Disease

Angioplasty

Percutaneous transluminal angioplasty has been well studied in the superficial femoral artery (SFA). The initial experience was characterized by good rates of technical success but poor long-term patency rates, especially in comparison to those achieved in the iliac arteries. As the understanding of the different dynamics of the femoropopliteal vessels has improved, better patient selection and refinement of techniques have led to improvement in outcomes.

The Society of Cardiovascular and Interventional Radiology (SCVIR) Transluminal Angioplasty and Revascularization (STAR) registry is a database of patients who underwent conventional angioplasty or other percutaneous intervention for lower extremity occlusive disease performed at seven hospitals over a 3-year period. Patients were followed for a total of 5 years with evaluations at 3, 6, and 12 months initially and then yearly thereafter. Assessment of long-term primary patency rates and associated patency predictive factors for patients undergoing femoropopliteal angioplasty was published in 2001.

A total of 219 limbs in 205 patients were included in the analysis. Patients with stenoses (78.5%) and occlusions (11%) were treated, and 6% of patients had concurrent stenosis and occlusion. Mean lesion length was 3.8 cm for stenotic lesions and 4.7 cm for occlusions. Clinical severity, classified by the Rutherford criteria ( Table 1 ), showed a distribution of 2%, 20%, 36%, 12%, 25%, and 0% for classes I through VI, respectively. Technical success rate was 95%. Primary patency rates at 12, 24, and 36 months were 87%, 80%, and 69%, respectively. Factors found to be associated with decreased patency rates were diabetes and poor runoff score ( Figure 2 ). The type of lesion (stenosis vs. occlusion) or the complexity of the lesion (classified according to the AHA task force classification categories 1–4) appeared to have no effect on the patency, although there were a very limited number of class 4 lesions. These patency results are higher than previously published rates. The authors attributed this to advances in equipment and techniques. They concluded that high long-term primary patency can be achieved with femoropopliteal angioplasty and that extending the spectrum of complex lesions treated by endovascular means may be warranted.

A meta-analysis including 19 studies from 1993 to 2000 included 923 balloon dilations. The patients were divided into four categories by combinations of their lesion type (stenosis vs. occlusion) and symptoms (claudication vs. critical limb ischemia [CLI]). Lesion length was less than 10 cm in all but one study. Combined 3-year primary patency rates were 61% for patients with stenosis and claudication, 48% for those with occlusions and claudication, 43% in patients with stenosis and CLI, and 30% for occlusion plus CLI. These rates were found to be statistically similar to those for primary stenting with regard to patients with claudication and stenosis, but they were inferior with respect to stenting for occlusion or critical limb ischemia.

One of the obstacles in the endovascular treatment of the SFA has been technical difficulties in crossing chronic occlusions, especially long-segment occlusions. The technique of subintimal angioplasty was developed to overcome this challenge. Met and colleagues compiled a systematic review of 23 cohort studies from 1966 to 2007 looking at outcomes using the subintimal angioplasty technique for infrainguinal occlusive disease. A total of 1549 patients were included. Heterogeneity between the studies was too significant to be able to perform a meta-analysis. Technical success ranged from 80% to 90%, with 1-year clinical success rates of 50% to 70%. Primary patency rates were almost 50% at 1 year, and limb-salvage rates were 80% to 90%, leading the authors to conclude that subintimal angioplasty was a useful technique for difficult lesions, especially for limb salvage in critical limb ischemia. The authors view this technique as a reasonable method of treating patients who have critical limb ischemia and who have contraindications to surgical treatment.

Angioplasty with Stenting

The use of stents was initially advanced to improve long-term patency rates from balloon angioplasty, especially with respect to treating longer-segment disease (>10 cm), in which angioplasty outcomes remained poor. Stenting helps to improve the initial angiographic outcome, reduces elastic recoil, and provides a scaffold in the setting of dissection.

The outcomes of studies assessing the utility of stenting have varied. Initial study results were disappointing, with several randomized trials failing to show benefit of stent placement over angioplasty alone. These findings led to the recommendation for stenting only in the setting of a suboptimal technical result following balloon angioplasty. However, these studies were done using balloon-expandable stainless steel stents, and more recent studies using self-expanding nitinol stents have shown significantly better outcomes with stenting. Also, there have been questions as to whether primary instead of optional stenting would lead to better outcomes. In the previously mentioned meta-analysis, the majority of studies involving stenting were performed with optional stenting. Two of the studies involved primary stenting, and when these were excluded from the analysis, a 1% to 3% reduction in long-term primary patency for stent placement resulted.

Three major randomized trials comparing primary nitinol stent placement with stent-assisted angioplasty have been reported and show differing results. The Femoral Artery Stenting Trial (FAST) studied outcomes with standalone percutaneous transluminal angioplasty (PTA) versus primary stenting with a single self-expanding nitinol stent. Only single short-segment lesions (<10 cm) were included in the study, with a mean lesion length of 45 mm for both groups. A total of 121 patients were randomized to PTA alone, and 123 were assigned to primary stenting. Technical success was achieved in 79% of the PTA group and 95% of the stenting group. At 1 year, restenosis rates determined by ultrasound were not statistically different between the two groups (38.6% in PTA, 31.7% in stent). Clinically, maximal walking distance was slightly improved in the stenting group, but there was no difference in resting ABI or change in Rutherford class. Stent fractures were also assessed owing to concern regarding nitinol stent fracture risk and possible subsequent increase in restenosis. Stent fracture was found in 12% of patients in the trial with no statistically significant increase in restenosis associated with the presence of fracture.

In the RESILIENT ^∗

∗ A Randomized Study Comparing the Edwards Self-ExpandIng LifeStent Versus Angioplasty-alone In LEsions INvolving The SFA and/or Proximal Popliteal Artery.

trial, 234 limbs were treated in 206 patients over a year and a half in 24 centers throughout the United States and Europe. Those included in the study had lesions shorter than 150 cm in cumulative length (if there was more than one lesion), had Rutherford class 1 to 3 clinically, and had at least one patent runoff vessel. Patients were randomized to primary stenting (134) or PTA alone (72). Mean lesion length in the stent group was 70.5 ± 44 mm and 64.4 ± 40.7 mm in the PTA group.

Forty percent of the patients in the PTA group underwent bailout stent placement because of residual stenosis of more than 30% or flow-limiting dissection after PTA. These patients were kept with the PTA group for analysis purposes but were considered to have had a target lesion revascularization (TLR) event and loss of primary patency at day 0. Technical success was better in the stent group compared to the PTA (95.8% vs. 83.9%). Freedom from TLR (defined as any reintervention upon the target lesion) was significantly better in the stent group than the PTA group at 6 and 12 months (98.5% and 87.3% vs. 52.6% and 45.1%). Primary patency rates at 6 and 12 months in the stent group were 94.2% and 81.3%, respectively, which was significantly better than for the PTA group, which were 47.4% and 36.7%, respectively. Stent fracture rate was 3% at 12 months and was not associated with any adverse clinical sequelae.

Clinically, both groups showed improvement; however, the stent group had significantly better outcomes clinically. The quality-of-life measurements were similar between the two groups, with the exception of walking distance scores, which were significantly better in the stent group. The authors concluded that for moderate-length lesions, primary stent placement with a self-expanding nitinol stent is superior to treatment with PTA alone.

The initial publication of the ABSOLUTE trial (Balloon Angioplasty Versus Stenting with Nitinol Stents in the Superficial Femoral Artery) showed a similar favorable result for primary stenting compared to angioplasty alone, but in a follow-up publication of the ABSOLUTE trial Schillinger and colleagues reassessed outcomes in their patients 2 years after their procedures to determine if the benefit initially seen with stenting was sustained. At 12 months, primary stenting had shown a morphologic and clinical benefit with respect to restenosis rates, walking capacity on the treadmill, and resting ABIs.

The study included 104 patients with severe intermittent claudication and/or tissue loss (Rutherford classes 3–5), with lesions longer than 30 mm and at least one patent runoff vessel. Subjects were then randomized to PTA plus optional stenting or primary stenting with nitinol stents. Mean target lesion length was 112 mm for the stent group and 93 mm for the PTA group. Two-year follow-up was performed in 98 of the patients. Restenosis rates were found to be significantly lower in the primary stenting group at 2 years (45.7% vs. 69.2%). There was no difference between the two groups with respect to Rutherford class upon follow-up but, although not statistically significant, there was a trend toward improved walking capacity and resting ABI in the stent group. Overall, reintervention rates were lower in the primary stent group.

The differences in findings between these trials are thought to mostly be a result of the characteristics of the lesions treated as well as possibly the size of the stent used. Longer lesions seem to have improved outcomes with the use of primary stenting, whereas shorter lesions (as treated in the FAST trial) have adequate outcomes with PTA alone and do not show improvement with the addition of a stent. The rates of restenosis seen in the ABSOLUTE trial were higher overall than those seen in other trials. The authors hypothesized that this was caused by the higher number of smaller-diameter stents used in their trial in comparison to others. In a subset analysis they found worse outcomes with respect to stenting in women with smaller vessels when compared to stenting overall. Also, in light of the findings of these trials, the concern for increased stent fracture rates with nitinol possibly leading to increased restenosis rates seems unfounded.

Future directions currently being studied for treatment of femoropopliteal artery occlusive disease are the use of drug-eluting stents and covered stents. To date, a number of trials have been completed assessing the performance of drug-eluting stents with non-medicated nitinol stents. Nearly all of these trials have failed to show dramatic benefit of medicated stents in the femoropopliteal segment. Medicated stents have been evaluated in the SIROCCO ^∗

∗ A Clinical Investigation of the SIROlimus Coated Cordis SMART Nitinol Self-expandable Stent for the Treatment of Obstructive Superficial Femoral Artery.

I and II trials as well as the STRIDES ^†

† A Study to Evaluate the Safety and Performance of the Dynalink-E, Everolimus Eluting Peripheral Stent System for Treating Atherosclerotic de Novo or Restenotic Native Superficial Femoral and Proximal Popliteal Artery Lesions.

trial. These studies have failed to prove significant benefit with the use of medicated stents over standard self-expanding nitinol stents. Using a different agent from those in either of the previous trials, paclitaxel, the most widely evaluated medicated stent is the Zilver stent (Cook, Inc., Bloomington, IN) but published results regarding this device are limited. It is likely that medicated stents add some benefit in treatment of these lesions, but it is also clear that recurrent stenosis will occur with this therapy as well. Medicated balloons have also shown some promise in reducing restenosis rates, but the application method for these devices and the types of lesions these will work best for remains to be determined.

Covered stents have been used for occlusive disease in the SFA and the most widely evaluated is the Viabahn endograft (W. L. Gore & Associates, Flagstaff, AZ). In a randomized comparison of covered stenting to angioplasty, the authors noted a marked improvement in initial technical success with the use of covered stents (95% vs. 66%) and sustained improvement in patency as assessed by duplex to 1 year (65% vs. 40%). Importantly, the longer the lesion, the more dramatic the improvement in outcome seemed to be. Covered stenting likely adds significant benefit when treating long-length lesions, but longer-term patency benefit remains to be assessed, and comparison with uncovered stents is being assessed in a separate randomized trial, the VIBRANT ^∗

∗ Viabahn versus Bare Nitinol Stent in the Treatment of Long Lesion (≥8 cm) Superficial Femoral Artery Occlusive Disease.

trial. Results from this trial are eagerly awaited to determine the benefit this technology has to add.