In the last five to seven years, there has been a bewildering array of new below-the-knee technologies. But the proof of benefit of these long balloons, drug-eluting stents and drug-coated balloons is still awaited. Yet, the evidence is beginning to emerge. Marc Bosiers, Dendermonde, Belgium told Interventional News that 12-month results of the prospective, randomised, multicentre, angio-controlled DESTINY trial comparing bare metal stents with drug-eluting stents show that the primary patency rates are 59% for balloon-expandable stents and 89% for drug-eluting stents, which is highly statistically significant (p<0.0001). This has led the investigators to conclude that this pivotal trial shows that there is an indication for primary stenting with drug-eluting stents in critical limb ischaemia patients with focal lesions. The DESTINY of drug-eluting stents clearly, is below-the-knee!
From the relatively well-established success in the aortoiliac or superficial femoral artery regions, a wave of treatment and innovation in endovascular therapies for critical limb ischaemia is geared towards below-the-knee vessels. Dedicated tools have improved the indications and the number of procedures. As occlusions are more prevalent than stenoses in the infrapopliteal arteries, there are now dedicated guidewires, dedicated long balloons and dedicated stents for the region. Experts point to the dedicated below-the-knee tools such as long low-pressure balloons and below-the-knee stents, either balloon-expandable stents, or self-expanding stents which have a role in making the difference in the treatment success or failure.
Angiologist Iris Baumgartner from Bern, Switzerland, says, “This is a field that has evolved so much over the last few years that I would call it revolutionary. When I started as an interventional trainee, below-the-knee was reserved for the high-profile interventionalists, as the material was so poor. There was indeed a high risk of failure, and the grave possibility of deteriorating the situation for the patient. Today, low profile wires and balloons have opened up a door for highly successful procedures.”
Gunnar Tepe, Rosenheim, Germany, agrees: “Technical success is certainly increasing with the use of better devices, especially wires and low profile crossing devices developed specifically for below-the-knee indications. There are currently several clinical trials underway, but at this point in time, there is no evidence as to what degree patients with critical limb ischaemia really benefit in terms of less restenosis. There is also clear data available that drug-eluting balloons and drug-eluting stents reduce restenosis.”
Role of infrapopliteal stenting
The first glimmers of evidence are beginning to establish the promise of endovascular treatments of below-the-knee regions for patients with critical limb ischaemia. It is generally agreed that there is a large diversity in lesions below-the-knee and that the precise role of stenting remains to be determined. At the CIRSE 2010 conference in Valencia, Spain, FE Vermassen told delegates “There is no reason to withhold stenting if the angioplasty result is not sufficient. When stenting, use a dedicated below-the-knee stent.”
Stenting has been established by Siablis (JEVT 2007) with 29 patients and mean lesion length of 13mm, showing a primary patency rate of 40.5% at 12 months, Scheinert (Eurointervention 2006) with 30 patients and a maximum lesion length of 30mm obtained a primary patency rate of 67% at 10 months. Bosiers (Eurointervention 2008) also showed that with 50 patients with a mean lesion length of 21mm had a primary patency rate of 63% at 12 months.
For long infrapopliteal lesions, the choice of treatment is more complex. Bosiers emphasises that “We have to make a distinction between treatment strategies based on the lesion configuration.
a) Long diffuse lesions (= majority of the patient population with critical limb ischaemia). For these patients, the optimal endovascular treatment consists of angioplasty with dedicated below-the-knee balloons and bailout stenting, using either self-expanding stents or balloon-expandable stents. Balloon-expandable stents are indicated for use in calcified lesions because they offer a high radial force, and in bifurcation lesions because they allow precise stent placement. Self-expanding stents are our preference in all other lesions.
b) Short lesions below 4cm in length: Single centre results report primary patency rates of 40% after angioplasty-only, 40–60% after implantation of bare metal stents and 80–85% for drug-eluting stents. These results are confirmed by the DESTINY study. This is the first randomised study comparing the long-term results with DES and bare metal stents in patients with criticla limb ischaemia and short focal lesions below-the-knee, with a maximum length of 40mm. Due to the good results at 12-months, we conclude that this pivotal trial shows there is an indication for primary stenting with drug-eluting stents in critical limb ischaemia patients with focal lesions.
The future of below the knee treatment
“The results of endovascular therapy for below-the-knee vessels will be further improved by the continuous technical evolution and new material developments. The two main innovations which will be interesting to follow in the future are drug-coated balloons and drug-eluting absorbable stents. There are many studies currently investigating the impact of treatment with drug-coated balloons in short and long lesions below-the-knee and, in follow-up the positive results from the coronary ABSORB trial with the polymer everolimus-eluting Bioresorbable Vascular Scaffold system. Abbott is planning an ABSORB BTK study, which will be conducted to evaluate the safety and efficacy of this bioresorbable vascular scaffold system in patients with severe claudication or critical limb ischaemia,” Bosiers said.
Speaking on further evolution, Tepe, who like Bosiers believes that drug-eluting bioabsorbable stents have the potential to be revolutionary, states that “In below the knee, better crossing devices either to stay in the lumen or re-entry devices would also be needed.”
Below the knee revascularisation: All or nothing
At the recent CIRSE 2010 conference, Jan H Peregrin, CIRSE president told delegates, “All accessible infrapopliteal lesions should be approached in patients with critical limb ishcaemia, no matter if they are TASC D type. By repeated percutaneous angioplasty, a secondary limb salvage could be maintained as high as 73%, even 10 years after procedure.
The paper he presented was titled “Angioplasty of below-the-knee arteries: long term follow-up and factors influencing clinical outcome.” Peregrin said that a group of 1,268 patients/1,445 lower limbs with critical limb ischaemia who had had infrapopliteal angioplasty performed, was retrospectively analysed. The average age of patients was 67 +/-10.8 years, 70% of the patients were male. Main indications to angioplasty were: gangrene (50.2%), non-healing ulcer (17.0%) and rest pain (15.2%). Lesions were mostly of TASC C and D type, with average length 15.1cm. The average number of arteries intervened per limb was 1.77. The criterion of clinical success was salvage of limb salvage with maximally transmetatarsal amputation.
Peregrin’s team achieved 89% technical success in the arteries they intended to treat. Primary limb salvage at one year was 76.1%. Secondary limb salvage was 84.4%, 78.3% and 73.4% at one, five, and 10 years follow-up, respectively. The most significant negative clinical condition influencing limb salvage rate was presence of gangrene prior angioplasty, the most significant feature positively influencing limb salvage rate was the number of patent arteries after angioplasty (primary limb salvage: 0 arteries-56.5%, 1 artery-73.1%, 2 arteries-80.4% and 3 arteries-83.0%).
This contrasted with the opinion of Vlad Alexandrescu, Department of Vascular Surgery, Princess Paola Hospital, Belgium who advocates revascularisation of a target vessel.
Although it remains hard to compare angioplasty with surgery, there is common agreement that an endovascular approach should even be the first choice treatment. Baumgartner says, “Due to the low complication rates and no need for bypass veins a wider spectrum of elderly, fragile patients can be treated, who really need treatment. I think we will see decreasing amputation rates in the coming years. But I also have to raise my finger at this point and say– it is like modern art, not everyone can do it! A fundamental caveat is that these techniques should be envisioned only in the hands of experienced operators who are capable of fast and proficient management of potential complications.
Bosiers agrees, “The primary approach in patients with critical limb ischaemia is minimally invasive endovascular treatment because many critical limb ischemia patients have diabetes, present with prohibitive comorbidities, or are poor candidates for surgery because of inadequate conduit or lack of suitable distal targets for revascularisation. This is confirmed by the current TASC II 2007 recommendations. Furthermore, endovascular therapy offers the advantages of local anaesthesia, the possibility of intra-arterial medication administrating, potentially reduced costs (even in anticipation of the need for re-intervention in many patients), and shorter hospital stays.
He sums it up with: “The final goal is, by early detection and adequate treatment, to reduce the amputation rate and increase the quality of life in patients with critical limb ischaemia.”
Roger Greenhlagh in London, UK, gives a vascular surgical perspective. There has indeed been an upsurge in below the knee interventions and this is an exciting area. The vascular surgeon has learned that proximal revascularisation should always take precedence over distal. Thus, aorto-iliac has precedence over femoral and profunda interventions which have precedence over popliteals which come ahead of below the knee intervention. These more proximal vessels are likely to produce a greater perfusion to the foot than more distal ones.
The endovascular below the knee technologies need to be judged on their own merit therefore, and not is association with proximal procedures if we want to learn about the tibial interventions in their own stand alone state.
The other burning issue is to go further than seeing a short-term anatomical correction from below the knee intervention and to seek long-term data on the ability of these technologies to save legs. The starting point thus has to be on a population of patients with critical limb ischaemia (ref 1981, BJS) and without proximal intervention followed for some years, five in the first instance. If these data appear and are convincing, many more patients will be referred for below the knee intervention, and open distal bypass with the attendant slow healing of often infected wounds will become virtually extinct.