Drug-Eluting Resorbable Scaffold Beats Angioplasty for Infrapopliteal Artery Disease

San Francisco — An everolimus-eluting stent with a resorbable scaffold showed superior efficacy in a randomized multicenter trial when compared with angioplasty for the treatment of patients with chronic limb threatening ischemia (CLTI) resulting from infrapopliteal artery disease.

The stent (Esprit BTK, Abbott Vascular) was also noninferior to angioplasty in terms of safety.

Presenting results of the LIFE-BTK trial here at the Transcatheter Cardiovascular Therapeutics 2023 congress, Ramon Varcoe, MBBS, MS, PhD, MMed, of Prince of Wales Hospital, Sydney, Australia, said that peripheral artery disease is a global epidemic, the most serious manifestation of which is CTLI.

"If not treated expeditiously, this could lead to high rates of amputation, which as we all know, has a severe impact on patients' quality of life, and even worse impact on their life prognosis, with prognosis rates worse than most cancers."

He said that for infrapopliteal or below-the-knee (BTK) arterial disease, treatment with angioplasty has proven superior to bypass graft surgery, but some limitations of angioplasty are elastic recoil, dissection, and restenosis, thus limiting its durability. Coronary drug-eluting stents showed promise in BTK procedures but can interfere with reintervention. Thus, LIFE-BTK compared a drug-eluting stent with resorbable scaffolding to surgery.

Esprit BTK is a drug-eluting resorbable scaffold consisting of a temporary scaffold backbone of poly(L-lactide) and a strut thickness of 99 μm. It is coated with everolimus and bioresorbable poly(D,L-lactide). Two platinum markers at each end provide radiopacity.

LIFE-BTK enrolled patients aged 18 years or older with CLTI associated with ischemic rest pain or minor tissue loss and who had infrapopliteal artery stenosis or occlusion. The trial was prospective, international multicenter, and single-blind and randomly assigned 261 patients aged 18 years or older in the ratio of 2:1 to Esprit BTK (n = 173) or to angioplasty (n = 88). Treatment of up to two target lesions was allowed with a total scaffold length < 170 mm.

The primary efficacy endpoint was superiority of Esprit BTK over angioplasty in terms of freedom of above-ankle amputation in the index limb, binary restenosis of the target lesion, and clinically driven target lesion revascularization evaluated at 1 year.

The primary safety endpoint, evaluated at 6 months, consisted of freedom from above-ankle amputation, major reintervention at 6 months, and perioperative mortality at 30 days.

An independent committee adjudicated clinical events, and core laboratories with assessors blinded to trial group assignment adjudicated imaging results and wound assessments.

Superior Efficacy, Noninferior Safety

Participants were about two thirds men, largely White, with about 15% of participants being Black/African American, and more than 90% of patients in each arm had hypertension. Lesion lengths were approximately 44 mm in each group with reference vessel diameters averaging 2.82-2.94 mm before intervention. Less than 4% in each group had severe lesion calcification.

Clinical follow-up rate at 1 year in the Esprit BTK arm was 90.2% and in the angioplasty arm 90.9%. Six patients in the former arm died vs five in the latter.

Varcoe showed a graph of the primary efficacy results at 453 days, the extra time being allowed to achieve a diagnostic ultrasound. In the Esprit BTK group, 74.2% of participants achieved the efficacy endpoint vs 47.9% of the angioplasty subjects (P < .0001).

"As you can see those, those bars start to diverge in about 5 months and continue to separate over time, showing clear superiority of the scaffold over angioplasty, absolute risk difference of 30.8% and a highly statistically significant P value," he said. Very similar primary efficacy outcomes were seen at 393 days.

At 1 year, the secondary efficacy endpoint of binary restenosis of the target lesion occurred in 24.2% of scaffold patients vs 46.5% of the angioplasty group (P < .0001). Another secondary endpoint, freedom from above-ankle amputation, 100% total occlusion of the target vessel, or clinically driven target lesion revascularization,  occurred in 82.5% of the scaffold group vs 70.4% in the angioplasty group (P = .0081).

The primary safety endpoint of freedom from a major adverse limb event plus perioperative death was 100% for angioplasty and 96.9% for Esprit BTK (P = .0019)

All subgroup analyses assessing interaction by sex, race, geographic region, or age showed Esprit BTK was superior to angioplasty, with relative risks ranging from 0.27 to 0.61.

"If this technology is approved by FDA, it will provide a new option for our patients with very difficult-to-treat disease, which will provide them additional durability and fewer reinterventions," Varcoe concluded. "And I think we all know deep down that's going to translate to improved clinical outcomes and few amputations."

David Kandzari, MD, of Peidmont Heart Institute in Atlanta, Georgia, was asked to comment on the study. He said that as with other vascular interventions, the ideal technology "would be first to provide a safe and effective antiproliferative therapy that would mitigate against restenosis and for scaffolding to prevent elastic recoil and reocclusion...and ultimately fulfill these two promises without the requisite of a permanent implant.

"Despite their common use in femoral popliteal disease, drug coated balloons had at best demonstrated inconsistent results below the knee, and drug coated balloons, therefore, are not approved for such indications."

He said that drug-eluting stents have demonstrated efficacy in this indication but that these studies have been limited to fairly discrete proximal disease.

"LIFE-BTK therefore represents one of the most rigorous trials in the space of endovascular interventions as a single line and randomized trial," Kandzari said, "showing a primary composite endpoint of both safety and effectiveness relative to conventional angioplasty."

Kandzari pointed to strengths of the study in that it used standardization of technique with independent adjudication of both imaging and wound healing assessments. "And the study population, too, was relevant to clinical practice, representing oftentimes underrepresented groups, including those with extensive disease burden [and] clinical severity," he said. "Importantly, in this study, nearly one third of the population will be women."

Panelist Jennifer Rymer, MD, of Duke University Medical Center in Durham, North Carolina, commented that she treats a lot of African American patients with CTLI and applauded the researchers for including those patients. "I think that this will be a groundbreaking new change in our practice," she said.

The trial results were published simultaneously with the presentation at TCT 2023 in The New England Journal of Medicine.

Varcoe reported receiving consulting fees/honoraria from Boston Scientific Corporation, Medtronic, Abbott, BD, Intervene, Surmodics, Philips, Nectero, Alucent, W.L. Gore, Vesteck, Bard Medical, Cook Medical, and R3 Vascular. He has equity, stock, or stock options in EBR Systems and has an executive role or ownership interest in Provisio Medical Inc. and Vesteck Inc. Kandzari received grant support/research contract from Medtronic, Teleflex, Biotronik, and CSI; consultant fees/honoraria from and is on the speaker's bureau of CSI and Medtronic; and has equity, stock, or options in Biostar Ventures. Rymer receives grant support/research contract from Chiesi, Abbott Vascular, Abiomed, and Pfizer. The study was funded by Abbott.

N Engl J Med. Published online October 25, 2023. Abstract

Transcatheter Cardiovascular Therapeutics 2023. Presented October 25, 2023.

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