New stent designs and drug-eluting technologies are intended to improve outcomes following femoropopliteal artery treatment for peripheral artery disease. Long-term patency following bare-metal stenting (BMS) is encouraging but remains unsatisfactory, with reported 1-year primary patency peaking at approximately 80%.1-5 Likewise, target lesion revascularization (TLR) rates for BMS also show room for improvement, with 1-year rates averaging approximately 13% in recent clinical trials.2-5

THE MAJESTIC TRIAL

MAJESTIC is a prospective, single-arm, multicenter clinical trial enrolling 57 patients across multiple sites in Europe, Australia, and New Zealand. Eligible patients had chronic lower limb ischemia and de novo or restenotic lesions in the native superficial femoral artery (SFA) and/or proximal popliteal artery (PPA). The primary endpoint was defined as 9-month primary patency assessed by duplex ultrasound as adjudicated by an independent core laboratory compared against a literature-derived performance goal. Major adverse events (MAEs) included all-cause death through 1 month, target limb major amputation, and TLR.

The Eluvia Drug-Eluting Vascular Stent System (Boston Scientific Corporation) is a self-expanding nitinol stent with a dual-layer coating and active layer consisting of the fluorocopolymer (polyvinylidene fluoride-co-hexafluoropropylene) and antiproliferative agent paclitaxel. The MAJESTIC study population for treating femoropopliteal artery lesions included a relatively challenging set of lesions:

  • 77% extended into the distal SFA
  • 9% extended into the PPA
  • 65% were severely calcified
  • 46% had total occlusions
  • 7.1-cm average lesion length

Figure 1. The decline in patency observed between 6 and 12 months in other trials testing similar technologies was not observed in MAJESTIC, which maintained a very flat curve throughout the first year, suggesting that sustained drug release may have a positive impact in this critical period when restenosis usually develops.

At 12 months, primary patency was 96.1% (49/51) and the MAE rate was 3.8% (2/53); both MAEs were TLRs. A 7.5% TLR rate was achieved at 2 years with no stent fractures. There were only two new TLRs between 1 and 2 years. These results represent the highest primary patency rates reported at 1 year and the lowest TLR rates at 2 years between comparable studies in the treatment of femoropopliteal lesions.6,7 In MAJESTIC, a reduction in primary patency between 6 and 12 months was not observed, a period of time during which patency has been seen to drop in other SFA trials (Figure 1).6,8-11

The Eluvia Drug-Eluting Stent system was designed to elute paclitaxel over time to match the restenotic process in the SFA. Prolonged paclitaxel elution is made possible by the PVDF-HFP (poly-vinylidene fluoride-hexafluoropropylene, a biocompatible fluoropolymer12) coating, which provides sustained and controlled drug release and does not inhibit endothelialization or promote thrombus formation in preclinical models.13,14 Several studies have suggested that restenosis following nitinol stenting in the SFA typically occurs within 12 months.15 This pattern was not observed in MAJESTIC, suggesting that sustained drug release may have a positive impact in this critical period when restenosis usually develops. No new TLR events occurred from 9 through 12 months, and the TLR rate remained low through 24 months.

CONCLUSION

The MAJESTIC clinical study showed that patients whose femoropopliteal arteries were treated with the Eluvia stent sustained a high patency with clinical improvement, low MAE rate, and an extraordinarily low TLR rate at 2 years. These results will have a significant impact on the future treatment of SFA lesions: if a stent is warranted, a dual-layer drug-eluting stent with prolonged paclitaxel elution seems to be the ideal solution from the current perspective.

1. Schillinger M, Sabeti S, Loewe C, et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med. 2006;354:1879-1888.

2. Krankenberg H, Schluter M, Steinkamp HJ, et al. Nitinol stent implantation versus percutaneous transluminal angioplasty in superficial femoral artery lesions up to 10 cm in length: the femoral artery stenting trial (FAST). Circulation. 2007;116:285-292.

3. Laird JR, Katzen BT, Scheinert D, et al. Nitinol stent implantation vs. balloon angioplasty for lesions in the superficial femoral and proximal popliteal arteries of patients with claudication: three-year follow-up from the RESILIENT randomized trial. J Endovasc Ther. 2012;19:1-9.

4. Bosiers M, Torsello G, Gissler HM, et al. Nitinol stent implantation in long superficial femoral artery lesions: 12-month results of the DURABILITY I study. J Endovasc Ther. 2009;16:261-269.

5. Matsumura JS, Yamanouchi D, Goldstein JA, et al. The United States study for evaluating endovascular treatments of lesions in the superficial femoral artery and proximal popliteal by using the Protege Everflex nitinol stent system II (DURABILITY II). J Vasc Surg. 2013;58:73-83 e71.

6. Dake MD, Ansel GM, Jaff MR, et al. Paclitaxel-eluting stents show superiority to balloon angioplasty and bare metal stents in femoropopliteal disease: twelve-month Zilver PTX randomized study results. Circ Cardiovasc Interv. 2011;4:495-504.

7. Dake MD, Ansel GM, Jaff MR, et al. Sustained safety and effectiveness of paclitaxel-eluting stents for femoropopliteal lesions: 2-year follow-up from the Zilver PTX randomized and single-arm clinical studies. J Am Coll Cardiol. 2013;61:2417-2427.

8. 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.

9. Lammer J, Bosiers M, Zeller T, et al. First clinical trial of nitinol self-expanding everolimus-eluting stent implantation for peripheral arterial occlusive disease. J Vasc Surg. 2011;54:394-401.

10. Dake MD, Scheinert D, Tepe G, et al. Nitinol stents with polymer-free paclitaxel coating for lesions in the superficial femoral and popliteal arteries above the knee: twelve-month safety and effectiveness results from the Zilver PTX single-arm clinical study. J Endovasc Ther. 2011;18:613-623.

11. Iida O, Takahara M, Soga Y, et al. One-year results of the ZEPHYR (Zilver PTX for the femoral artery and proximal popliteal artery) registry: predictors of restenosis. JACC Cardiovasc Interv. 2015;8:1105-1112.

12. Stone GW, Teirstein PS, Meredith IT, et al. A prospective, randomized evaluation of a novel everolimus-eluting coronary stent: the PLATINUM (a prospective, randomized, multicenter trial to assess an everolimus-eluting coronary stent system [Promus Element] for the treatment of up to two de novo coronary artery lesions) trial. J Am Coll Cardiol. 2011;57:1700-1708.

13. Wilson GJ, Huibregtse BA, Stejskal EA, et al. Vascular response to a third generation everolimus-eluting stent. EuroIntervention. 2010;6:512-519.

14. Iida O, Uematsu M, Soga Y, et al. Timing of the restenosis following nitinol stenting in the superficial femoral artery and the factors associated with early and late restenoses. Catheter Cardiovasc Interv. 2011;78:611-617.

15. Chin-Quee SL, Hsu SH, Nguyen-Ehrenreich KL, et al. Endothelial cell recovery, acute thrombogenicity, and monocyte adhesion and activation on fluorinated copolymer and phosphorylcholine polymer stent coatings. Biomaterials. 2010;31:648-657.

Prof. Stefan Müller-Hülsbeck, MD, EBIR, FCIRSE, FICA
Professor of Radiology
Head of the Department of Diagnostic and
Interventional Radiology/Neuroradiology
Diako Hospital
Flensburg, Germany
muehue@diako.de
Disclosures: Consultant for Boston Scientific Corporation and has received consulting fees, speaker honorarium, and support for accommodation and traveling when presenting Boston Scientific Corporation–related data.