Treatment of femoropopliteal lesions with the low-dose Lutonix drug-eluting balloon reduces late lumen loss with safety comparable to that of control angioplasty, according to LEVANT I trial results published in the January 2014 issue of JACC: Cardiovascular Interventions.
The LEVANT I (Lutonix paclitaxel-coated balloon for the prevention of femoropopliteal restenosis) trial sought to evaluate the safety and efficacy of the Lutonix drug-eluting balloon (Lutonix/Bard) coated with 2µg/mm2 paclitaxel and a polysorbate/sorbitol carrier for treatment of femoropopliteal lesions. The study was the first-in-human randomised trial of low dose drug-eluting balloon versus uncoated balloon angioplasty.
“Percutaneous treatment of peripheral vascular disease is associated with high recurrence rates. Paclitaxel-coated balloons at 3mg/mm2 formulated differently have shown promising results with reduced restenosis,” the authors, led by Dierk Scheinert, Center of Vascular Medicine, Heart Center Leipzig/Park Hospital, Leipzig, Germany, write.
Lesion criteria for enrolment included single de novo or restenotic (non-in-stent) lesions (operator-determined >70% stenosis, length ≥4cm and ≤15cm, reference vessel diameter ≥4mm and ≤6mm).
One hundred and one patients with Rutherford class 2 to 5 femoropopliteal lesions were randomised between June 2009 and December 2009 at nine centres to treatment with Lutonix drug-eluting balloon (n=49) versus uncoated balloons (control group [n=52]), stratified by whether balloon-only treatment (n=75) or stenting (n=26) was intended. The primary endpoint was angiographic late lumen loss at six months. Secondary outcomes included adjudicated major adverse events (death, amputation, target lesion thrombosis, reintervention), functional outcomes, and pharmacokinetics.
Demographic, peripheral vascular disease, and lesion characteristics were matched, with mean lesion length of 8.1±3.8cm and 42% total occlusions.
At six months, by intention-to-treat analysis, late lumen loss was 58% lower for the Lutonix drug-eluting balloon group (0.46±1.13mm) than for the control group (1.09±1.07mm; p=0.016). Composite 24-month major adverse events were 39% for the drug-eluting balloon group, including 15 target lesion revascularisations, one amputation, and four deaths versus 46% for uncoated balloon group, with 20 target lesion revascularisations, one thrombosis, and five deaths.
A pharmacokinetics substudy showed biexponential decay with peak concentration (Cmax) of 58.4±83.2ng/ml and total observed exposure (AUCall) of 73.2±45.3ng h/ml. For successful drug-eluting balloon deployment excluding eight malfunctions, six-month late lumen loss was 0.39mm and the 24-month target lesion revascularisation rate was 24%.
The trial investigators write that this randomised study provides the first human proof of the antirestenotic effect of the Lutonix drug-eluting balloon in treating lower extremity occlusive disease, with a 58% reduction in six-month late lumen loss for the Lutonix drug-eluting balloon-treated group versus the uncoated balloon control group (0.46 vs. 1.09mm).
“These findings compare well to first-generation drug-eluting balloons where higher doses of paclitaxel (3mg/mm2) resulted in mean late lumen loss of 0.4mm (17) and 0.5mm (18), despite the fact that the vessels treated in this study had smaller diameter with longer lesion length and a higher frequency of total occlusion. The antirestenotic benefit of the drug-eluting balloon was observed when used alone or in combination with stents. Safety in this patient population persisted out to 24 months,” they say.
In the paper, the authors explain that the Lutonix drug-eluting balloon uses polysorbate and sorbitol as the drug carrier selected “to evenly distribute the paclitaxel in a uniform, durable coating for endovascular drug transfer”. They add, “Pharmacokinetics analysis showed transient serum levels after treatment with the Lutonix drug-eluting balloon that are much lower than those reported for pharmaceutical infusions, with comparable elimination (27).”
In conclusion, Scheinert et al note that “these data demonstrate the safe use of the low-dose Lutonix drug-eluting balloon to attenuate restenotic responses across various procedural approaches (drug-eluting balloon used alone, with provisional stenting, or after stenting) out to 24 months. Treatment of femoropopliteal lesions with the novel Lutonix drug-eluting balloon is feasible, with similar safety and less late lumen loss than has been reported for uncoated balloon angioplasty.”