Drug-coated balloons to improve femoropopliteal artery patency: Rationale and design of the LEVANT 2 trial.

BACKGROUND: Atherosclerotic peripheral artery disease (PAD) is common and results in limitations in quality of life and potential progression to limb loss. Options for therapy include medical therapy, supervised exercise, surgical revascularization, and, more recently, endovascular therapies to restore arterial perfusion to the limb. Endovascular revascularization has evolved over the past 2 decades, from percutaneous transluminal angioplasty (PTA) to self-expanding stents, atherectomy, laser angioplasty, and drug-eluting stents. Despite impressive technologic advances, PTA remains the standard of care at many institutions and is the recommended primary treatment modality for femoral-popliteal PAD according to current American College of Cardiology Foundation/American Heart Association guidelines. However, restenosis after PTA is common. Therefore, a significant clinical need remains for a device that is able to achieve more durable patency than PTA but does not require a permanent implant. Drug-coated balloons (DCBs) have the potential to address this need. Several randomized controlled clinical trials of PTA balloons coated with different formulations of paclitaxel have been conducted in Europe (N Engl J Med 2008;358:689-699) (Circulation 2008;118:1358-1365) (Circ Cardiovasc Interv 2012;5:831-840) (JACC Cardiovas Interv 2014;7:10-19) and demonstrated more durable efficacy than PTA with comparable safety. These studies were limited by small sample sizes and powered solely for an angiographic primary end point. The pivotal LEVANT 2 trial was designed in collaboration with the US Food and Drug Administration to demonstrate safety and efficacy in a large population and to obtain US Food and Drug Administration approval. METHODS: A prospective, multicenter, single-blind trial comparing the Lutonix DCB (Bard Lutonix; New Hope, MN) versus PTA for treatment of femoropopliteal PAD (LEVANT 2) is the first US-based 2:1 randomized controlled trial of 476 patients with femoral-popliteal PAD designed to demonstrate superior efficacy and noninferior safety of a novel paclitaxel DCB compared with PTA. The primary efficacy end point is primary patency at 12 months. The primary safety end point is composite freedom at 12 months from perioperative death, index limb amputation, reintervention, and limb-related mortality. A series of important secondary end points include physical functioning, quality of life, revascularizations, and alternative measures of patency. To minimize bias potential for confounding variables, LEVANT 2 (1) excluded patients stented after predilation before randomization, (2) incorporated very stringent criteria for bailout stenting, (3) did not count bailout stenting as a target lesion revascularization or failure of any end point, (4) required a blinded clinician to perform clinical evaluations at follow-up, and (5) required clinical assessment before review of duplex ultrasound results. CONCLUSIONS: LEVANT 2 represents the first US-inclusive multicenter, randomized controlled trial to assess the safety and efficacy of a novel DCB compared with PTA as primary therapy for symptomatic PAD on the background of standard medical therapy.

Retrospective Review of Directional Atherectomy and Drug-Coated Balloon Use in a PAD Safety-Net Population.

BACKGROUND: Peripheral artery disease (PAD) is associated with high morbidity and mortality, particularly once patients develop critical limb threatening ischemia (CLTI). Minorities and vulnerable populations often present with CLTI and experience worse outcomes. The use of directional atherectomy (DA) and drug-coated balloon (DCB) during lower-extremity revascularization (LER) has not been previously described in a safety-net population. OBJECTIVE: To review demographic and clinical characteristics, and short- intermediate term outcomes of patients presenting to a safety-net hospital with PAD treated with DA and DCB during LER. METHODS: In this retrospective, observational cohort study, chart review was performed of all patients who underwent DA and DCB during LER for PAD from April 2016 to January 2020 in a safety-net hospital. RESULTS: The analysis included 58 patients, with 41% female, 24% Black/African American, and 31% Hispanic. From this group, 17% spoke a non-English primary language and 10% reported current or previous housing insecurity. Most (65%) presented with CLTI and had undergone a previous index leg LER (58%). The combination of DA and DCB was efficacious, resulting in low rates of bail-out stenting (16%) and target-vessel revascularization (26%) at 2 years. Low complication rates (tibial embolism in 12% and vessel perforation in 2% of cases) were also observed. Most patients (67%) with Rutherford category 5 experienced wound healing by 2 years. CONCLUSION: In this safety-net population, the majority presented with CLTI and a previous LER of the index leg. The combination of DA and DCB resulted in low complication rates, and good short-intermediate outcomes in this frequently undertreated population.