By Thomas Zeller
Following successful first-in-man trials (THUNDER, FEMPAC) using the Paccocath/Cotavance coating technology (Bayer, iopromide & 3µg/m2 paclitaxel), two recently presented major pivotal trials confirmed the safety and efficacy of paclitaxel-eluting balloons in the endovascular treatment of femoropopliteal arterial disease. The IN.PACT SFA I & II trials using the IN.PACT Admiral device (Medtronic, urea & 3µg/m2 paclitaxel) enrolled overall 331 patients at 57 sites across Europe and the USA in a 2:1 randomisation scheme, and the LEVANT 2 trial including 476 patients who had been treated with the Lutonix 35 balloon (Bard-Lutonix, polysorbate/sorbitol & 2µg/m2 paclitaxel).
The pooled randomised multicentre IN.PACT SFA I & II trials revealed that clinically-driven target lesion revascularisation rates were significantly lower with the drug-eluting balloon as compared to those achieved with angioplasty (2.4% vs. 20.6%, p<0.001). Similarly, the primary patency rate achieved with IN.PACT Admiral was 82.2%, while the primary patency achieved with angioplasty was 52.45% (p<0.001). Primary patency at 360 days calculated by Kaplan-Meier survival estimates was 89.8% for the drug-eluting balloon group and 66.8% for the angioplasty group.
In the LEVANT 2 trial, the primary patency at 12 months defined as freedom from both restenosis and target lesion revascularisation was 65.2% for the drug-eluting balloon which was superior to control angioplasty (52.6%, p=0.015) demonstrating superior efficacy. At 12 months, the freedom from clinically-driven target lesion revascularisation in the Lutonix group was 87.7% compared to 83.2% in the control group (p=0.208).
In both studies no device specific side-effects were reported, and no major amputation occurred. Thus, there was no safety concern regarding wash off of a part of the antiproliferative drug into the distal vasculature.
Are both of the studies comparable? In brief, both studies enrolled only claudicants with femoropopliteal lesions. Lesions in the LEVANT 2 trial were slightly less challenging as compared to the IN.PACT SFA trial regarding mean lesion length (63mm vs. 89mm) and total occlusions (21% vs. 25.8%), and unlike in previous femoropopliteal premarket approval studies, bailout stenting was not considered a failure. Interestingly, the outcome of the control cohorts is almost identical regarding primary patency (52.6% in LEVANT 2 vs. 52.45% in IN.PACT SFA) and freedom from target lesion revascularisation (83.2% vs. 79.4%). Thus, blinding for the treatment, as it was part of the LEVANT 2 protocol but not of the IN.PACT SFA protocol, did obviously not impact the trial outcome; blinding of the duplex physician or technician regarding the treatment modality which the patient received does hardly impact a decision regarding a reintervention in a non-invasive follow-up setting. Opposite to an invasive angiographic follow-up, where it is much more likely that the knowledge of the treatment modality might impact the decision for an ad-hoc target lesion revascularisation, the indication for a reintervention following a non-invasive diagnostic examination is most likely based on the patient’s clinical symptoms. Thus, the differences in drug-eluting balloon performance regarding primary patency and freedom from clinically-driven target lesion revascularisation seem therefore to attribute to the different coating technologies. Preclinical animal studies have shown that not every coating technique is equally effective. However, only a direct clinical comparison of both drug-eluting technologies could finally answer this question.
The major message of the both peripheral interventional landmark trials is that a balloon based treatment approach for TASC II A & B femoropopliteal lesions achieves good clinical one-year outcomes regarding freedom from clinical-driven target lesion revascularisation, which is the outcome patient and payers are mainly interested in. Of note, not every drug-eluting balloon is alike; each single device deserves its own clinical efficacy and safety studies.
Thomas Zeller is head, Department of Angiology at Universitäts—Herzzentrum Freiburg-Bad Krozingen, Bad Krozingen, Germany