Yesterday, at the CX ilegx Collaboration Day, the difficulties and challenges of managing peripheral arterial disease were reviewed. Experts discussed the optimum imaging approaches, the benefits of exercise therapy, and novel methods of enhancing wound healing. The management of diabetic vascular disease and ischaemic foot, including the role of stenting, was also explored during the day.
Jim Reekers (Amsterdam, The Netherlands), in the first talk of day, addressed the question “What is the optimum method of vessel imaging in people with diabetes?” by reviewing the “pros” and “cons” of the available options—duplex-Doppler ultrasound, computed tomography (CT) angiography, magnetic resonance (MR) angiography, and digital subtraction angiography. For example, he said that the “pros” of CT angiography were that it was non-invasive, could be rapidly performed, and had better spatial resolution than MR angiography, but the “cons” were that it involved “high-doses of radiation, had artifacts in heavily calcified arteries, and had limited usefulness in many patients with diabetes”. Reekers also looked at value of using anatomical imaging to direct revascularisation in the diabetic foot, noting that it was “at least unclear” how useful such an approach was.
In his talk, Robert Hinchliffe (London, UK) looked at whether there were any specific tests for identifying which patients with diabetic foot needed to undergo revascularisation. He commented that transcutaneous oxygen (TcPO2) of ≥25mmHg predictor healing, ankle pressure of <50mmHg or ankle branchial index of <0.5 predictor of amputation, and perfusion assessment “was helpful, but not in isolation”.
Moving on to treatment approaches, Nicola Troisi (Florence, Italy) reported that, last year, his centre started a supervised exercise programme for diabetic foot patients. He commented: “Overall, in the patients who completed the 16-week programme, there was a significant increase of TcPO2 (46.3mmHg pre vs. 58.8mmHg post; p=0.02), maximum walking distance (188.8m pre vs. 444.7m post; p=0.001), and walking impairment questionnaire (0.57 pre vs. 0.78 post; p<0.001).”
Andrew Boulton (Manchester, United Kingdom) also reviewed therapies for treating the diabetic foot—looking at adjunctive techniques for healing ulcers. He claimed the view that “a wound would not heal because of diabetes” was not true. “A diabetic foot wound will heal if three factors are attended to: first, there needs to be an adequate arterial inflow; second, infection should be aggressively managed; and third—and most frequently neglected—all pressure should be kept off the wound and its margins,” Boulton explained. Furthermore, he added that some patients with a diabetic foot ulcer, as a result of chronic sensorimotor diabetic peripheral neuropathy, have lost “the gift of pain”. Therefore, to the confusion of healthcare professionals, these patients are able to walk on a large plantar neuropathic ulcer. He noted: “Enforced offloading—using either a total contact cast or a removable cast walker rendered irremovable—has been shown in randomised controlled trials to be effective in speeding wound healing.” According to Boulton, what you “take off” wounds (eg. pressure, slough and other callus/dead tissue) is more important than “what you put on”—“Despite the fact that we have hundreds of different dressings that are promoted for the use of wound healing in diabetes, there is no evidence whatsoever that any particular dressing is superior to another.”
William Jeffcoate (Nottingham, UK) and Harvey Chant (Truro, UK) reviewed wound healing also—looking at, respectively, how to measure wound healing and the use of autologous cell suspension. Chant reported that, after reviewing the use of autologous cell suspension in difficult wound cases, the treatment was promising, easy to use for both patients and staff, appeared to be cost-effective, and durability seemed good.
The others topics that were discussed during the course of the day included: The King’s College Hospital open access vascular diabetic foot pathway, revascularisation of the ischaemic foot, and “To stent or not to stent—that is the question”.
During the “To stent” section of the “To stent or not to stent—that is the question” session that was held in the afternoon of the CX ilegx Collaboration Day, Martin Funovics (Vienna, Austria) reviewed data for the rationale for using stent grafts for TASC II C & D femoropopliteal lesions. Looking at data for the Viabahn covered stent graft (Gore), he noted that a lesson learnt from the VIPER study was to not “oversize the graft”. Funovics also discussed data from the VIASTAR study, which found that the Viabahn stent graft was associated with significantly better one-year primary patency than was a bare metal stent (78.1% vs. 53.5%, respectively; p=0.01) in patients with long lesions.
Also in the “To stent” section, Yann Goueffic (Nantes, France)—in his talk “The expected benefit of drug elution to the same new nitinol scaffold stent”—outlined the clinical trial programme for the drug-eluting stent Eluvia (Boston Scientific). For example, he explained that the aim of the new EMINENT study was to “confirm the effectiveness” of the stent for treating superficial femoral artery and/or proximal popliteal artery lesions (up to 140mm) compared with bare metal stents. Goueffic added that the study, of which he is a principal investigator, also aims to provide “additional data, including health economics data”.
For the below-the-knee section of the “To stent or not to stent—that is the question” session, Ramon L Varcoe (Sydney, Australia) spoke about the bioresorbable vascular scaffold (Abbott Vascular). He noted that the scaffold “offers several advantages over metal stents” and that it “can be implanted safely within the tibial vasculature”. “Excellent immediate angiographic results and promising 12-month patency can be achieved,” Varcoe added.
Drug-coated balloons: the importance of dosage
By Renu Virmani
Drug-coated balloons (DCBs) are now increasingly becoming the standard of care for peripheral arterial disease (PAD) treatment. While all commercially available DCBs use paclitaxel, the drug dose plays a very important role in the overall safety and efficacy.
We recently performed an independent blinded analysis of two leading DCBs that have received FDA and CE mark approval in order to understand the pathologic changes that occur in the downstream vascular bed following arterial dilatation in a swine model. The purpose was to compare the Lutonix (Bard) 035 (paclitaxel dosage 2µg/mm2) to the IN.PACT Admiral (Medtronic: FreePacTM paclitaxel eluting formulation, dosage 3.5µg/mm2). Two configurations were assessed; a single balloon application and three overlapping balloon applications. Similar biological effects were observed locally in the femoral artery for the two balloons. However, downstream effects were significantly different. At 90 days, the percentage of downstream vascular changes following DCB dilatation was 5–25 times less for Lutonix 035 as compared to the IN.PACT Admiral. Moreover, the drug levels in the skeletal muscle and coronary band were 30–100 times greater for the IN.PACT Admiral DCB as compared to Lutonix 035 DCB group.
Safety considerations of DCB treatment of PAD are especially important when treating diabetic and critical limb ischaemia patients, whether for superficial artery or below-the-knee disease, as they have compromised microvasculture. The data from our head-to-head blinded controlled study provides relevant safety considerations where wound healing is a major concern especially in critical limb ischaemia patients who require frequent interventions. The Lutonix 035 DCB is coated with 2µg/mm2 paclitaxel drug using a novel polysorbate/sorbital carrier that balances safety and efficacy as compared to the IN.PACT Admiral which uses 3.5µg/mm2 paclitaxel, FreePacTM Coating utilising urea carrier formulation associated with greater distal embolisation.