(Leipzig, Germany) January 30, 2020 -- During this an update on clinical trials and new data in peripheral vascular disease, including femoral, below-the-knee (BTK) and critical limb ischemia (CLI), Robert Lookstein, MD (Icahn School of Medicine at Mount Sinai, New York City) presented 10-year findings of the LONG DES-BTK study of the use of drug-eluting stents (DES) in the treatment of BTK disease.
The study seeks to expand on the existing datasets of DES, as part of continuing efforts to determine when and in whom this technology is best suited.
“We hope that this LONG-DES dataset will inform practitioners that even in lesions where you require three overlapping coronary stents, results are safe and effective in achieving limb salvage with very, very low rates of reintervention,” Dr Lookstein said.
In infrapopliteal disease, the use of balloon angioplasty with bail-out bare metal stenting (BMS) in cases of residual stenosis or flow-limiting dissection is associated with poor long-term patency and the need for reintervention. Patients with BTK disease frequently have comorbid diabetes, renal insufficiency, and have a history of tobacco smoking – all of which are associated with long, calcified stenoses and occlusions that are difficult to treat with balloon angioplasty.1
“For those patients who are failing balloon angioplasty, we have yet to realize the ideal technology to overcome these limitations,” Dr Lookstein commented.
Exploring BTK treatment options to date, he further explained that investigations of drug-coated balloons (DCB) have so far been unsuccessful in improving upon outcomes of balloon angioplasty. “We have two negative prospective randomized trials and a third trial where we don’t have 12-month follow up yet.”
The first of these two prospective randomized trials, IN.PACT DEEP, included 358 CLI patients randomized to receive IN.PACT Amphirion DCB (Medtronic) or plain balloon angioplasty. No statistically significant differences were detected in the primary efficacy outcomes of clinically-driven target lesion revascularization and late lumen loss at one year.2
The second prospective randomized trial of BTK DCB was BIOLUX P-II, which included 72 patients randomized to receive either the Passeo-18 Lux DCB (Biotronik) or plain balloon. Here, the primary endpoint of six-month patency loss was not significantly inferior in the DCB group relative to plain balloon. Major amputations were also similar at 12 months.3
As such, he continued, numerous investigators globally have looked to scaffolds as a viable solution. “The only implants to date that have demonstrated efficacy have been balloon-expandable coronary drug-eluting stents,” he said.
“There are ongoing studies evaluating novel technologies. One of these is a self-expanding polymer-based drug-eluting paclitaxel stent – studied in the SAVAL trial.4 Another is on the MicroStent [Micro Medical Solutions] which is a bare metal, interwoven stent for the BTK circulation. Both of these trials are currently enrolling and the preliminary results are not yet publicly available.5”
In the meantime, the body of data on the use of short coronary balloon-expandable stents for the treatment of infrapopliteal disease has grown. These have recently been summarized in a systematic review and meta-analysis by Varcoe et al (2019), which included data pertaining to seven randomized controlled trials with mid-term (12-month) follow-up, with the conclusion that DES significantly improved rates of primary patency, freedom from reintervention, and freedom from major amputation compared to control therapy (plain balloon angioplasty, BMS, or DCB). The investigators also found that stents coated in sirolimus analogues were more effective than paclitaxel.1
These randomized trials included relatively short lesions with mean lesion lengths ranging from 15.9 mm to 34 mm.1 The only included trial with lesions over 100 mm – the IDEAS trial6, which randomized a real-world patient cohort with long BTK lesions to DCB or coronary DES – had multiple issues, as Dr Lookstein described: “There were multiple DES allowed in the study. The only published data that has ever been presented publicly was of the six-month follow up. Lastly, DES was compared to an arm of heterogeneous DCB. So it was much more of a real-world registry dataset of all-comers, randomizing two different technologies for long lesions.”
No DCB or DES are currently approved for the BTK circulation in the US, Dr Lookstein noted. Turning to his own centre’s approach, he explained: “Our clinical protocol at Mount Sinai is to cross infrapopliteal lesions, perform prolonged long balloon angioplasty, and then perform a subsequent repeat angiographic assessment of the lesion that was treated. Unfortunately, we find that in [up to] 30% of cases, there is significant elastic recoil or flow-limiting dissection requiring the use of stent implantation.
“For the past 10 years now, we have been using a single coronary DES platform for infrapopliteal lesions below the knee: the Xience everolimus-eluting stent [Abbott Vascular]. We have placed stents in the BTK circulation for patients with CLI in over 375 patients now, and we have been following all of our patients with a routine clinical and imaging protocol.”
A key aim of the LONG DES-BTK study at Mount Sinai was to ascertain how safety and efficacy outcomes related to the number of stents implanted in a single case. Like most coronary stents being applied in the peripheries, the Xience stent has a maximum length of 38 mm, and as such even a relatively short lesion of 45 mm would require the implantation of two overlapping stents. In the cohort of 75 patients in LONG DES-BTK, lesion lengths ranged from around 50 mm to 150 mm, requiring the tandem implantation of two to four stents.
“These were all patients that were treated with this technology not as a primary therapy, but after bail-out following suboptimal angioplasty. So the patient had to undergo revascularization, fail balloon angioplasty (defined as either significant elastic recoil with a >50% residual luminal narrowing, or a flow-limiting dissection).
“In this very challenging subset of long infrapopliteal lesions that have failed balloon angioplasty, amputation-free survival for the entire cohort (including Rutherford 4, 5, and 6) was 73% at one year. When you look at the cohort broken down by Rutherford category, for the Rutherford 4 and 5 patients, amputation-free survival at one year was over 90%, and for the Rutherford 6 patients this fell down to almost 50%. So we are seeing significant benefit for amputation-free survival favoring the use of this technology in Rutherford 4 and 5 patients.”
- Varcoe RL, Paravastu SC, Thomas SD, et al. The use of drug-eluting stents in infrapopliteal arteries: an updated systematic review and meta-analysis of randomized trials. Int Angiol. 2019;38(2):121-135.
- Zeller T, Baumgartner I, Scheinert D, et al; IN. PACT DEEP Trial Investigators. Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP randomized trial. J Am Coll Cardiol. 2014;64:1568-1576.
- Zeller T, Beschorner U, Pilger E, et al. Paclitaxel-Coated Balloon in Infrapopliteal Arteries: 12-Month Results From the BIOLUX P-II Randomized Trial (BIOTRONIK'S-First in Man study of the Passeo-18 LUX drug releasing PTA Balloon Catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries). JACC Cardiovasc Interv. 2015;8:1614-1622.
- The DES BTK Vascular Stent System vs PTA in Subjects With Critical Limb Ischemia (SAVAL). ClinicalTrials.gov. Available online at https://clinicaltrials.gov/ct2/show/NCT03551496. Accessed January 30, 2020.
- A Clinical Evaluation of the MicroSTent® PeripherAl Vascular SteNt in Subjects With Arterial Disease Below the Knee (STAND). ClinicalTrials.gov. Available online at https://clinicaltrials.gov/ct2/show/NCT03477604. Accessed January 30, 2020.
- Siablis D, Kitrou PM, Spiliopoulos S, et al. Paclitaxel-coated balloon angioplasty versus drug-eluting stenting for the treatment of infrapopliteal long-segment arterial occlusive disease: the IDEAS randomized controlled trial. JACC Cardiovasc Interv. 2014;7:1048-1056.