The results of two trials presented at the recent Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium in Washington, DC, could have dramatic implications for the future of stenting in the superfemoral artery (SFA). The outcomes of the ‘Local Taxan With SHort Time and Exposure for RedUctioN of Restenoisis in Distal ArtERies (THUNDER) trial and Femoral Artery Stenting Trial (FAST) have highlighted both the benefits of using paclitaxel-coated angioplasty balloons and the limitations of SFA stenting in relatively short lesions.
Dr Gunnar Tepe, assistant professor of radiology at the Eberhard-Karls-University of Tuebingen, Germany, and principal investigator of the THUNDER trial told Vascular News, “The six-month outcomes gives us evidence that drug-coated balloons reduce restenosis in the superficial femoral artery.” In the THUNDER trial, 154 patients from three centres were randomised to receive an uncoated balloon (n=54), an uncoated balloon in combination with paclitaxel (n=52), or the paclitaxel-coated angioplasty balloon, called the Paccocath catheter (48). Among other inclusion criteria, patients had an occlusion or stenosis of >2cm and a Rutherford score of 3 to 5.
All treatment groups were well balanced for patient characteristics. Those in the uncoated balloon arm had an average pre-procedure lesion length of 7.3cm, compared with 6.7cm and 6.5cm for the uncoated balloon-plus-paclitaxel and the Paccocath arms, respectively. Study participants had 1.7 lesions treated on average, and the mean degree of stenosis ranged from 87.7% to 90.7% between the three arms.
Mean late lumen loss at six-month follow-up was significantly reduced in the Paccocath arm (P<0.01) when compared with those receiving uncoated balloons. The target lesion revascularization rate at six months was 29.6% (n=16) in the uncoated balloon arm, 25% (n=13) in the uncoated balloon-plus-paclitaxel arm and 6.3% (n=3) in the Paccocath arm. Binary restenosis at six months in the uncoated balloon arm was identified in 21 patients, in the uncoated balloon-plus-paclitaxel arm in 22 patients and in the Paccocath arm in seven patients. Patients in the uncoated balloon arm had mean Rutherford scores of 3.1 at baseline and 1.6 at six-month follow-up, compared with 3.4 and 2.0 in the uncoated balloon-plus-paclitaxel arm and 3.4 and 1.2 in the Paccocath arm, respectively. In a critical commentary, Dr Ivan De Scheerder, University Hospital Leuvens in Belgium, congratulated Tepe on the trial design and the good results thus far. However, he added that the approximate 20% study dropout rate and the lack of a comparison group of patients treated with paclitaxel-coated stents were limitations. In conclusion, DeScheerder said, “I have some concerns about the reproducibility of the local paclitaxel delivery using this balloon sytem. Furthermore, the bulk release of paclitaxel, which we know can result in vessel wall toxicity, late restenosis and especially late thrombosis is a concern.” In a subsequent press conference, Tepe told reporters that “the balloon allows the drug to be delivered in a much shorter period of time and does not leave behind a coated stent, which itself can cause problems down the road. Also, because the coating on the stent remains after the drug has been completely delivered to the vessel wall, it may cause undesired effects later.” The Paccocath catheter is manufactured by Bavaria Medizin Technologie GmbH. Twelve-month late data from FAST presented by Dr Hans Krankenberg, Center for Cardiology and Vascular Intervention, Hamburg, Germany, showed that Nitinol stenting is not superior to stand-alone percutaneous transluminal angioplasty (PTA) in relatively short lesions. This contrasts with data from the ABSOLUTE study, which indicated that there was a benefit for SFA stenting in longer lesions. The FAST trial comprised 244 patients in 11 European centres, with 121 randomised to treatment with PTA and 123 randomised to receive a stent (Luminexx – Bard). All patients had single lesions 1cm-10cm long with 70% to 100% restenosis at baseline. Major inclusion criteria comprised a Rutherford classification of at least two, and a single de novo lesion. The primary study endpoint was binary restenosis (at least 50% stenosis on ultrasound) at 12 months. The researchers hypothesised that stent implantation would reduce one-year binary restenosis from 45% in the PTA arm to 25% in the stent arm, and assumed a 15% loss-to-follow up rate, to eventually enrol a total of 244 patients. Except for a lower prevalence of males in the stent arm (63% vs. 75%), pertinent patient characteristics were well matched between the study arms. Crossover from the PTA arm to the stent arm became necessary in 13 patients. The 12-month results revealed that the incidence of restenosis was 38.6% in patients treated with PTA vs. 31.7% in patients who received nitinol stents in an intent-to-treat analysis (P=0.377). There were no major procedural complications and limited major adverse events. There were ten stent fractures accounting for 12% of the study group, but fracture had no impact on restenosis. An analysis according to treatment received, restenosis rates were still equivalent between stent- and PTA-treated patients. There was a trend toward reduced restenosis in patients receiving stents who were male diabetics and who smoked. According to the study, there was a trend toward lower restenosis rates in the female PTA cohort although these differences were not statistically significant. There was a 35% reduction in restenosis in patients who received stents where the vessel was totally occluded and a 39% reduction in patients with more than one distal vessel occluded, but these differences were also not statistically significant. Target lesion revascularisation (TLR) rate was 18.3% (21/115) in the PTA group and 14.9% (17/114) in the stent arm (p=0.595). Multivariate analysis showed that patients with lesions longer than 5cm or who had total occlusion had an increased risk of restenosis, as were patients who received a stent, had hyperlipidemia/hypertension, were diabetics or more than one distal vessel occluded; women; and smokers were at increased risk of restenosis. In addition, patients with normal cholesterol levels had lower rates of restenosis when treated with stenting. Krankenberg said that the FAST trial failed to demonstrate the superiority of the Luminexx nitinol stent over stand alone PTA in the treatment of patients with SFA lesions 1-10cm in length (a 44% relative risk reduction for restenosis). However, he added that stent implantation appeared to be associated with a tendency towards a lower risk of restenosis in a wide variety of patient and lesion subgroups. “Prospective randomised trials in specific patients cohorts such as diabetics, patients with total chronic occlusions, or patients with impaired distal run-off, are warranted,” he concluded. In a critical assessment, Dr James D Joye, from El Camino Hospital, Mountain View, CA, said that ‘knee-jerk’ default to stenting that exists in coronary space does not apply to the periphery. However, he added that the ramifications of in-stent restenosis and the difficulties associated with the problem, the trial supports a bail-out role for lesions of <5cm in length. In conclusion, Joye said that more data is eagerly awaited from similarly robust trials (RESILIENT) and results may improve with better stent designs and drug delivery platforms such as the Zilver-PTX (Cook). He added that non-stent endovascular solutions would continue to emerge and mature. These data contradict with data from the ABSOLUTE study which indicated that there was a benefit for SFA stenting in longer lesions.