Drug-Eluting Balloons are Better for Below-Knee Lesions Than Sirolimus-Eluting Stents

Why is it not a good idea to use sirolimus-eluting stents as a primary treatment for below-the-knee lesions?

Below-the-knee vessels have a mean lesion length of 130 to 170 mm. This is not practical for a sirolimus-eluting stent (SES). Drug-eluting balloons (DEBs) and SESs are two totally different approaches, but not to critical limb ischemia. Just to the lesion. Critical limb ischemia (CLI) cannot be treated with a SES, because only short lesions can be treated with an SES. In fact, in the two major randomized trials that we have concerning SES implantation in below-the-knee lesions (with the Xience stent from Abbott Vascular), the main lesion length was less than 40 mm.

DEBs are an important new tool for below-the-knee interventions, because they match the anatomy present in CLI. DES do not match the anatomy; treating short lesions only takes place in a very few cases of CLI. In one retrospective analysis published by Schmidt et al, the mean lesion length for below-the-knee lesions was 173 mm.¹ This means the operator would have to to place 6 or 7 SESs in places where stent compression is very likely, possibly leading to permanent distortion and/or thrombosis, things we definitely want to avoid. It is better to use a DEB, and when a stent is necessary, to implant a drug-eluting stent. However, the requirement in CLI is typically just for spot stenting and perhaps only in the proximal segment of the femorotibial vessels. 

You presented one-year results of the DEBATE-BTK trial (Drug Eluting Balloon in peripherAl inTErvention For Below The Knee Angioplasty Evaluation) at the VeithSymposium. Can you tell us about it? 

Leonardo Bolognese, MD, FESC, Director, Cardiovascular and Neurological Department, and Francesco Liistro, MD, chief of the Cardiovascular Intervention Unit, San Donato Hospital, are the principal investigators of this trial and together with the chief of vascular surgery, Guido Bellandi, MD, and the chief of the diabetic unit, Lucia Ricci, MD, constitute a multidisciplinary team involved in limb salvage. DEBATE BTK looked at patients with diabetes and critical limb ischemia undergoing revascularization with either the Medtronic Invatec In.Pact Amphirion DEB or an uncoated balloon, in occluded or stenotic tibial vessels with lesions of at least 40 mm. We presented one-year follow-up data on 132 patients.

Our study was meant to be an angiographic study, so the primary endpoint is bilateral angiographic restenosis at 12 months. We saw a significant and important reduction in restenosis in the DEB group, with a mean relative risk reduction of 64%  (27% restenosis in the DEB group vs. 74% in the control group, P<0.001). DEB use also showed a mean relative risk reduction of 68% in vessel occlusion at 12 months (17% re-occlusion in the DEB group vs. 55% in the control group, P<0.001). These are important angiographic endpoints. The advantage of the DEB in restenosis and reocclusion is maintained, irrespective of the length of the lesion, and irregardless of the baseline vessel condition, whether it is restenotic or occluded, and also irregardless of the technique applied for the revascularization, whether intraluminal or subintimal. The advantage of DEB use is kept in all types of revascularization. 

Do you have recommendations from your experience for the use of DEBs?

Inflow lesions must be treated first. Femoral popliteal intervention should be performed initially if required. There must be distal runoff; otherwise, there is no sense in putting in a DEB. The circulation in the foot must be, let’s say, present. Before the DEB is placed, we do a standard balloon angioplasty along the entire segment. Depending on the length of the lesions, we then use 1, 2 or 3 DEBs, overlapping each DEB by at least 5 mm (10 mm is better). There should be a one-to-one ratio between the DEB and the vessel. It is not worth it to oversize the balloon with respect to the vessel diameter, because on follow-up, we could see in 3% of the cases that there is an ectatic effect from the drug delivery in the vessel.

The patient receives double antiplatelet treatment for one month. It is very important to check every week for the first four weeks to make sure the vessel is open. One of the mechanisms that can lead to the vessel occlusion is dissection. The recanalization that can be obtained in a 100-150 mm occlusion of the vessel tends to be mostly in a subintimal fashion. That means that a large dissection is created, and the flap of the dissection can create an abrupt vessel closure. In these cases, we cannot say that the DEB did not function, because it is not the fault of the drug, but the technique of application itself that may have some complications. 

How have you attempted to avert this complication?

We do continuous follow up of the lesion in the first four weeks. If there is an occlusion, we can see what type of occlusion it is and immediately treat it — perhaps put in a drug-eluting stent, for example. The drug placed by the DEB will always maintain its effect, but if you let the vessel close, then at follow-up you will have an occlusion for certain. 

How did patients in DEBATE BTK fare in terms of limb salvage?

There was a significant reduction in target lesion revascularization with use of a DEB, but there was no impact on limb salvage. We had only one major amputation in the control group and zero amputation in the drug-eluting balloon group. For us, this is standard practice, but it is not what we see in the literature. The very low rate of major amputation is probably due to different aspects. First, patients were randomized in the study when the wire was passed. When you pass the wire, the revascularization can be performed. Second, we maintain an extremely close observation of our patients after hospital discharge. The foot clinic sees patients 2x week for the first four weeks, and then 1x week for the first 3 months. If the healing process is not progressing, an echo is done immediately. If the vessel closes, we will reopen it. With this kind of follow-up, it is difficult for patients to lose a limb. It is a very important point for a cath lab that wants to start with a CLI program. You must have an agreement made between the interventionalist and the foot clinic specialist that there will be very close contact with the patient. The healing process must occur under very strict observation.

I believe DEBs will become the standard for below-the-knee interventions. We are talking about only one DEB at this time: the Medtronic In.Pact DEB. The rest have no proof at this point. Future research in this area will be similar to what occurred with the study of drug-eluting stents in the coronary arteries — we will need to compare the results of different DEB platforms regarding efficacy and safety. Being able to do so will be very important, because otherwise the data can be confused. However, all the clinical studies that we have at this time, whether retrospective or randomized, concern only the use of the In.Pact. 

What is the difference between the In.Pact and other drug-eluting balloons?

The drug used is always the same, paclitaxel. We have tried different platforms before. For example, the Aachen Resonance Elutax. It behaved like a conventional balloon, however, and the drug delivery was not adequate in our experience. The most tricky thing is how the paclitaxel is loaded in the balloon surface and the spacer that allows for maintenance of the drug concentration in the vessel wall for at least 2 to 3 months. If the drug is delivered but it goes away, there is no effect. That has been the problem for most of the old, second-generation DEBs.

Francesco Liistro, MD, can be contacted at francescoliistro@hotmail.com.

Reference

1. Schmidt A, Piorkowski M, Werner M, Ulrich M, Bausback Y, Bräunlich S, et al. First experience with drug-eluting balloons in infrapopliteal arteries: restenosis rate and clinical outcome. J Am Coll Cardiol. 2011 Sep 6; 58(11): 1105-1109.