Vascular Disease Management Speaks with John Laird, MD, RESILIENT Trial Investigator

Describe the inclusion criteria for patients in the RESILIENT trial

Patients were included in the trial if they had lifestyle-limiting claudication (Rutherford categories 1–3) of at least 6 months’ duration and were candidates for angioplasty or stenting. They had to have de-novo or restenotic (not stented) lesions in the superficial femoral artery (SFA) and/or proximal popliteal artery.

What types of lesions were treated in this trial?

The target lesion(s) had to meet the following criteria: (a) De-novo or restenotic lesion(s) located within the native SFA (1 cm below the origin of the profunda femoris artery) and/or proximal popliteal artery (3 cm above the knee joint). If the lesion(s) was/were restenosed or reoccluded, prior percutaneous transluminal angioplasty (PTA)-only treatment (no previous stent placement) must have occurred > 6 months prior to the study procedure. (b) The target lesion(s) had angiographic evidence of stenosis or restenosis ≥ 50% or occlusion and was/were amenable to PTA alone or primary stenting. The target vessel reference diameter was ≥ 4.0 mm and ≤ 7.0 mm and therefore appropriate for treatment with stent diameters of 6.0 and 7.0 mm. The total length of the lesion or series of lesions was ≤ 150 mm, and there was angiographic evidence of at least one vessel runoff to the foot.

How long will these patients be followed?

Data reported in the current manuscript (Circulation: Cardiovascular Interventions) were through 12 months (6 and 12 months). Patients in the RESILIENT study were followed through 3 years (6, 12, 24 and 36 months). Subsequent analysis of the longer-term data will be completed and submitted for publication at a later date.

How many centers participated in the RESILIENT trial? What were the operator requirements for participation?

Twenty-four sites in the United States and Europe participated in the randomized portion of the RESILIENT study. All operators were experienced stent users and experienced in peripheral endovascular procedures. Operators included interventional cardiologists, interventional radiologists and vascular surgeons.

Tell us about the various subanalyses of the RESILIENT results. What do these analyses tell us about bare-metal stenting in the SFA and popliteal artery?

The RESILIENT trial was designed as an intention-to-treat study to compare the results of angioplasty to a primary stent strategy. Patients were randomized to either the angioplasty group or primary stent group following successful crossing of the most distal lesion with a guidewire and uninflated angioplasty balloon. Patients who were randomized to the angioplasty group, but the PTA procedure either resulted in a flow-limiting dissection or significant elastic recoil with a residual stenosis of > 30%, could be treated with a stent (i.e., bailout stent). Per protocol, angioplasty patients who failed repeated PTA attempts and required a bailout stent were considered a target lesion revascularization (TLR) and a failure of primary patency. Although not designed or powered to study the provisionally stented patients (i.e., bailout stent group), two post-hoc subset analyses were performed. The first post-hoc subset analyzed patients according to the treatment received; that is, angioplasty versus the combined stent group (primary stent patients and provisional/bailout-stented patients). The second post-hoc analysis compared the results of PTA and PTA plus provisional stenting to the primary stent group. This analysis was the same as the a priori intention-to-treat analysis except that the bailout/provisional-stent patients were not treated as PTA failures. The as-treated analysis demonstrated that the patients who were successfully treated with angioplasty alone had relatively short lesions compared to the combined stent group (47.7 ± 32.6 mm vs. 63.3 ± 41.9 mm;

Describe the LifeStent’s design and deployment. Are there unique features to this stent?

The LifeStent® Vascular Stent System (Bard Peripheral Vascular, Inc., Tempe, Arizona) is composed of a nitinol self-expanding stent pre-loaded on a tri-axial delivery catheter with an ergonomic deployment handle. The nitinol stent is designed with a multidimensional helical architecture. The stent struts form a true helix and are connected by angled bridges, each offset from the previous bridge. Since the bridges connect a helical structure, their pattern is also helical. This unique design is engineered to conform to the bending, compression and torsion of the SFA and proximal popliteal arteries. Its dynamic vessel conformability and flexible helical design may afford some degree of fracture resistance, demonstrated by the low fracture rate in the RESILIENT study at 12 months (3.1%). The delivery system is composed of a 6 Fr tri-axial delivery catheter with braided sheath technology. It is designed to reach all lesions in the SFA and proximal popliteal artery. The System Stability Sheath technology (tri-axial sheath) is designed to absorb friction between the delivery system and the introducer sheath and other points of friction along the delivery system encountered during use. This allows a smooth retraction of the delivery sheath, which can lead to accurate stent placement. The ergonomically designed handle enables the user to choose deployment options. The operator can use the thumbwheel to facilitate accurate initial deployment and then can choose additional rapid deployment options to ensure the stent is delivered quickly, easily and accurately.

What were the major adverse clinical events (MACE) in the RESILIENT trial?

MACE in the RESILIENT trial was defined as 30-day death, stroke, myocardial infarction, emergent surgical revascularization, significant embolization in the target limb, thrombosis of the target vessel and worsening of at least one Rutherford category of chronic limb ischemia. Freedom from MACE at 6 and 12 months for the primary stent group was 93.1% and 85.8%, respectively.

What has the stent fracture rate been on average with previous SFA stents?

The stent fracture rate in the RESILIENT trial was 3.1% at 12 months. The SIROCCO I (Bare and Sirolimus-Coated SMART Stent) study reported an 18.2% fracture rate at 6 months, and the SIROCCO II trial reported an 8% fracture rate at 6 months. Bosiers et al reported an 8% fracture rate with the PROTÉGÉ EverFlex Self-Expanding Stent at 12 months. Low fracture rates have also been seen with the Absolute stent in the Schillinger study, and more recently with the Zilver PTX stent in a multicenter registry.

What was the late loss (i.e., at 6 or 9 months) in the stented patients versus the PTA patients in RESILIENT?

Since angiography was not performed routinely in the follow-up of patients in the RESILIENT trial, late loss following PTA or stenting was not calculated. Patency was assessed with Duplex ultrasonography, and clinical outcomes were evaluated by assessment of the rate of TLR. The TLR rate was reported at 6 and 12 months. TLR was defined as any repeat percutaneous intervention or bypass surgery of the target lesion because of a return of ischemic symptoms. The freedom from TLR rate at 6 months was 98.5% for the primary stent group versus 52.6% for the angioplasty group (p What was the subacute thrombosis rate in the stent versus angioplasty patients? Acute or subacute stent thrombosis did not occur in the RESILIENT study.

Is the LifeStent applicable in popliteal vessels at the knee joint?

The RESILIENT study did not evaluate the use of the LifeStent® Vascular Stent System in the popliteal arterial segment that crosses the knee. The study evaluated the use of the LifeStent® Vascular Stent System in the SFA and proximal popliteal artery from 3 cm above the knee joint to 1 cm below the origin of the profunda femoris artery. The LifeStent® Vascular Stent System is the only currently marketed bare-metal stent that is approved for use in the SFA and proximal popliteal artery. There is experience with the use of this stent in other segments of the popliteal artery from a multicenter European registry. The results were quite satisfactory, but use of the LifeStent in the mid and distal popliteal artery is an “off-label” use of this device.

What is the projected durability of vessel patency in the LifeStent patients? What is the average restenosis rate in PTA patients?

Primary patency was measured at both 6 and 12 months using Duplex ultrasound (DUS). Patency was defined as continuous flow through the target lesion area as evidenced by DUS. DUS evaluations were analyzed by an independent core laboratory. Treatment areas that demonstrated an increase in the peak systolic velocity ratio (PSVR) ≥ 2.5 suggesting a > 50% reduction in luminal diameter and/or underwent TLR were considered to have lost primary patency. The primary patency rate for the primary stent group was 94.2% versus 47.7% for the angioplasty group at 6 months (p In your opinion, will stenting in the SFA and popliteal arteries become the standard approach for revascularization? The data from RESILIENT and the Schillinger study would suggest that primary stenting is the preferred strategy for moderate-length lesions in the SFA and proximal popliteal artery. For focal lesions ( 15 cm in length), but stenting will no doubt continue to play an important role when there are suboptimal angioplasty results. We also do not have good comparative data between stenting and any of the currently available atherectomy devices, so it remains difficult to know what role atherectomy will play in the future.

What future role will bare-metal stents like the LifeStent play compared to drug-coated stents in SFA and popliteal intervention?

That’s a very good question, and I think we will have to wait and see what the results will be from the important randomized trials. We should see results from the Zilver PTX trial this fall. The perceived added benefit of a drug coating on the stent will have to be balanced against the additional cost of a drug-coated stent. Drug-eluting balloons are a very intriguing and promising approach to femoropopliteal and infrapopliteal disease, but again, we will need to see more data from randomized trials. The amount of data that is out there (THUNDER trial, etc.) is still relatively limited.

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Dr. John R. Laird is Medical Director at U.C. Davis Vascular Center in Sacramento, California. He is an internationally renowned interventional cardiologist who has lectured and performed endovascular procedures around the world. His practice focuses on interventions for carotid artery disease, abdominal and thoracic aortic aneurysmal disease, renal artery disease and peripheral artery disease. Dr. Laird is known for innovation, teaching vascular interventions to other physicians, and his role in organizing and conducting clinical trials of new therapies for vascular disease.