Drug-coated balloon technology is unlikely to be a successful “stand alone” treatment for the majority of medium and long length superficial femoral artery lesions, the voting results from CX2015 implied. The voting showed that the audience felt that drug-coated balloon use was best suited to short lesions. The randomised controlled trial data for drug-coated balloons are mostly based on short lesions and 57% of the audience voted “no” to the question, “Is drug-eluting balloon technology likely to be a successful standalone treatment for the majority of medium and long length superficial femoral artery lesions?” The session in which the vote was held was titled “Leaving nothing behind” and also saw the presentation of the ILLUMENATE first-in-human study 24-month results. These were favourable for the Stellarex drug-coated balloon (Spectranetics), and came close on the heels of updates on the Lutonix drug-coated balloon (Bard) and the IN.PACT Admiral drug-coated balloon (Medtronic). Atherectomy as a pretreatment also received a boost.
For the first time, CX voters also found support for atherectomy, but as a pre-treatment to the use of drug-coated balloons as described in the DEFINITIVE AR trial or as a pre-treatment to the use of stents. The majority, 77%, supported the motion “pretreatment of superficial femoral artery lesions before drug-coated balloon has CX 2015 audience support.
Thomas Zeller, Bad Krozingen, Germany, explained that “Drug-coated balloons add benefit to the endovascular approach to treat femoropopliteal disease but that there are still limitations such as recoil, calcium and dissections.”
Previous research has shown that circumferential calcification is a negative predictor for successful outcome with drug-coated balloon angioplasty. “Directional atherectomy is one of the most interesting pretreatment plaque modulating or plaque removing options available, after cutting or scoring balloons have been shown not to be very effective at this. The removal of ex-centric plaque and calcified plaque serves to reduce the problem of early recoil that limits the use of drug-coated balloon angioplasty outcome,” he said. Zeller also noted that the large majority vote favouring the use of atherectomy as a pretreatment were akin to a mandate to the industry to support large-scale randomised controlled trial to prove this concept.
In previous years, atherectomy has failed to elicit CX voter backing as a definitive treatment option in the superficial femoral artery. In 2014, 57% of the CX audience voted “no” to the motion, “I would use atherectomy for some superficial femoral artery lesions”. In 2013, 68% voted against the motion “atherectomy is the answer for the superficial femoral artery technology”.
This year’s vote shows that there is increasing support for atherectomy as a pre-treatment option rather than a definitive treatment and that the technique is clearly currently in favour of being used prior to drug-coated balloon or stents in order to reduce the risk of thrombosis. A member of the audience asked whether atherectomy should be the first option for isolated popliteal lesions considering there was a desire to leave nothing behind. Zeller, responding, said that it was frequently observed that isolated popliteal lesions were focal calcified lesions and for that indication, he considered atherectomy “an excellent first option followed by angioplasty or stenting”. “However, if we are talking about evidence to support this, there is none,” he clarified.
CX delegates at the session also heard updates on the Stanza bioresorbable scaffold (480° Medical) and Shockwave Lithoplasty for calcified artery from Andrew Holden, Auckland, New Zealand.
Stephan Duda, Berlin, Germany, presented the results of the 24-month ILLUMENATE first-in-human study. These showed that the primary patency rate (as measured by Duplex Core lab evaluation) was 80.3% at 24 months. At 12-months, the primary patency rate was 89.5%.
“The freedom from clinically-driven target lesion revascularisation rate (as determined by the clinical events committee adjudication) was 85.8% at 24 months and it was 90% at 12 months,” Duda said.
In the study, researchers evaluated Stellarex in 50 patients with 58 lesions in a cohort that required predilatation with an uncoated balloon before the inflation of the drug-coated balloon. The mean age of the cohort was 69 years. The mean age of patients was 69.0±9.3 years; Thirty four per cent of patients had diabetes and 80% had hypercholesterolemia; Eighty six per cent were Rutherford Class 3 at baseline; the mean lesion length was 7.2cm; nearly 14% had severe calcification and the mean stenosis at baseline was 75%.
The vessel patency was associated with a significant and sustained functional improvement as resulted by the walking impairment questionnaire and by the treadmill test patient subset. There were no cardiovascular deaths or amputations reported throughout the 24-month follow-up schedule in this cohort, demonstrating the high safety profile,” Duda said.
He continued: “This study demonstrates the safety and efficacy of Stellarex for the treatment of femoropopliteal disease up to two years. The primary patency of 89.5% and 80.3% match the highest benchmark of reported rates at one- and two-years respectively. There is also significant functional benefit observed with improved walking distance, observed up to two years.”
Duda told CX Daily News: “Stellarex employs a next-generation manufacturing technology and coating formulation. This combination allows for an effective dose of paclitaxel to be transferred to the treatment site using a low drug dose density of 2µg/mm2. Pre-clinical work has shown this coating results in high coating stability with limited drug loss and an effective amount of drug in the arterial wall through 28 days.”
There is a robust clinical programme for Stellarex that is actively underway and will include up to 1,300 patients in five studies, Duda concluded.
IN.PACT SFA clinical trial update
Gunnar Tepe, Rosenheim, Germany, presented the 12-month results from the pivotal randomised trial evaluating the safety and effectiveness of the IN.PACT Admiral drug-coated balloon.
“IN.PACT SFA is a rigorously designed trial that provides level I clinical evidence supporting the safety and effectiveness of the IN.PACT Admiral when used to treat lesions in the superficial femoral and proximal popliteal arteries,” Tepe said.
The trial is a prospective, randomised, international, 57-site trial comparing the outcomes of treating a lesion with the paclitaxel-coated IN.PACT Admiral vs. standard percutaneous transluminal angioplasty using an uncoated balloon.
A total of 331 patients with claudication or rest pain (Rutherford clinical category 2–4) with single de novo or non-stented restenotic lesions ≥4cm and ≤18cm or chronic total occlusions ≤10cm were randomised 2:1 to drug-coated balloon (n=220) or angioplasty (n=111). Data was independently evaluated by blinded duplex ultrasound and angiographic core labs and by a blinded clinical events committee.
Tepe said: “Baseline clinical, angiographic and lesion characteristics were well balanced between treatment groups. Mean lesion length was 8.94±4.89cm in the drug-coated balloon arm vs. 8.81±5.12cm in the angioplasty arm (p=0.815), representing the longest lesions evaluated to-date in a randomised drug-coated balloon trial.”
A total of 59.3% of lesions in the drug-coated balloon arm were calcified vs. 58.4% in the angioplasty arm (p=0.097), and 25.8% of lesions in the drug-coated balloon arm were total occlusions vs. 19.5% in the angioplasty arm (p=0.222).
“At 12 months, primary patency in the drug-coated balloon arm (freedom from clinically-driven target lesion revascularisation and freedom from restenosis as determined by duplex ultrasound PSVR≤2.4) was superior to the angioplasty arm (89.8% for the drug-coated balloon vs. 66.8% for the angioplasty arm, Kaplan-Meier analysis at day 360 showed that p<0.001). Clinically-driven target lesion revascularisation was statistically lower for the drug-coated balloon arm vs. the angioplasty arm (2.4% vs. 20.6%, p<0.001). Regarding clinical endpoints, we can conclude that patients treated with IN.PACT Admiral perform more favourably than angioplasty in terms of quality of life and walking capacity and angioplasty treated patients require 88% more interventions to achieve the same clinical outcome,” Tepe said.
“Patients are being followed out to five years post-procedure and two-year data are forthcoming,” Tepe concluded.
Dierk Scheinert, Leipzig, Germany, spoke on the topic “New insights from Levant 2 randomised data” that included data from subgroup and post-hoc analysis. “Levant 2 demonstrated superior patency for Lutonix against angioplasty with a 29.4% improved patency over angioplasty. The device was effective in a challenging patient population and showed target lesion revascularisation rates of 89% that were consistent in both the clinical trial and real-world registry,” he said.
Scheinert noted that Levant 2 had demonstrated the safety of Lutonix showing low rates of re-intervention for thrombosis and embolism. “Patients who received Lutonix DCB reported clinical benefits in Levant 2 and showed sustained improvement in Rutherford class and improvement in self-reported walking distance scores” he said.
Fabrizio Fanelli, Rome, Italy, outlined the current status of drug-coated balloon use in the superficial femoral artery. “There are more than 10 drug-coated balloons that are commercially available in Europe. All of them are based on the use of the same drug, paclitaxel, but the dosage is different, varying between 2µg/mm2 and 3.5µg/mm2. Moreover, each drug-coated balloon has a different excipient and a different coating technology,” he said. Most drug-coated balloons have passed their proof-of-concept test, but few have offered high-quality clinical evidence and programmes, even fewer have delivered best-in-class outcome, he emphasised.
Fanelli highlighted that studies such as IN.PACT SFA, LEVANT-2 and ILLUMENATE FIH were all multicentre studies with results that have been validated by independent core labs and that these data were essential in evaluating the quality of evidence and the quality of outcomes. “Only the most reliable data must be taken into consideration. There is no drug-coated balloon ‘class effect’. Each drug-coated balloon is to be judged upon the existence and value of its own data,” he stated.
Drug-coated balloons are cost-effective
Michael Jaff, Boston, USA, told CX 2015 delegates that while there are no prospective data collection studies, two publications have demonstrated that drug-coated balloons are a cost-effective alternative to angioplasty.
Jaff said: “Using current modelling, drug-coated balloons cost the system less than angioplasty, bare metal stents and drug-eluting stents, due to the lower target lesion revascularisation rates. It is critical that future randomised trials of one revascularisation technology include direct measurements of cost of care.”
He told delegates that the future was to be all about economic value and that in the previous week, the US payer system was in the process of reviewing the cost, efficacy and outcomes of all peripheral artery interventions for patients with intermittent claudication.
Jan B Pietzch and colleagues, publishing in Catheterization and Cardiovascular Interventions (2014), in studying the impact on payers and providers of the four main endovascular strategies for the treatment of infrainguinal peripheral artery disease in the USA and Germany, showed that drug-coated balloons and drug-eluting stents, compared to bare metal stents and percutaneous transluminal angioplasty, are associated with lower probabilities of target lesion revascularisation and therefore, cost savings for payers. Another publication, from BC Kearns and colleagues, published in the British Journal of Surgery in 2013, that set out to perform an economic evaluation of the cost-effectiveness of endovascular enhancements to percutaneous transluminal balloon angioplasty with bail-out bare metal stents for infrainguinal peripheral arterial disease, found that the use of drug-coated balloons represents a cost-effective alternative to the use of angioplasty with bail-out bare metal stents.
Jaff made the point that comparing the cost of using drug-coated balloons with the costs of percutaneous transluminal angioplasty, bare metal stents and drug-eluting stents was a “complex proposition”.
“Device costs are only one part of the equation. If the procedure offers greater durability, as defined by reduction in clinically driven target lesion revascularisation, the cost of care for that patient with peripheral artery disease will be lower than a comparable device requiring repeat interventions over a defined period of time,” Jaff concluded.
Direct balloon angioplasty
The panel agreed that more data were needed on whether pre-dilatation was needed before drug-coated balloon angioplasty was performed or not and called for a trial to compare the outcomes achieved with drug-coated balloon use after pre-dilatation to those achieved with direct angioplasty with drug-coated balloon.
Leaving something in
Speaking on the paradigms and importance of lesion lengths and types in the afternoon session on increasing lesion length options and various stent controversies, William Gray, New York, USA, made the point that lesion length is the only clearly identified driver of long-term outcomes. He drew attention to the fact that “Short-term outcomes may also be affected with increasing stent usage with increasing lesion length. Chronic total occlusion and diabetes do not appear to effect outcomes. The calcification grading is problematic, but likely has implications for both short- and long-term outcomes and adjunctive/specialised therapies may mitigate this effect.
Holden noted that five years ago lesion length had had a direct impact on patency with the technology that was available then. “Now with an armamentarium that consists of drug-coated balloons, biomimetic stents, drug-eluting stents, covered stents and atherectomy, we are saying that that paradigm is changing. Are we seeing less impact of lesion length on patency?” he asked. Gray noted that in the main, lesion length was the main driver of patency but that newer technologies and adjunctive therapies could modify the longer lesions in the drug-coated era and that he remained optimistic about this development.